American Journal of Obstetrics and Gynecology

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery

There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27-4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I-II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57-0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07-2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results.

Relugolix combination therapy in Black/African American women with symptomatic uterine fibroids: LIBERTY Long-Term Extension study

In the LIBERTY Long-Term Extension study, once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) substantially improved uterine fibroid-associated heavy menstrual bleeding throughout the 52-week treatment period in the overall study population. Black or African American women typically experience a greater extent of disease and symptom burden of uterine fibroids vs other racial groups and have traditionally been underrepresented in clinical trials. This secondary analysis aimed to assess the efficacy and safety of relugolix combination therapy in the subgroup population of Black or African American women with uterine fibroids in the LIBERTY Long-Term Extension study. Black or African American premenopausal women (aged 18-50 years) with uterine fibroids and heavy menstrual bleeding who completed the 24-week randomized, placebo-controlled, double-blind LIBERTY 1 (identifier: NCT03049735) or LIBERTY 2 (identifier: NCT03103087) trials were eligible to enroll in the 28-week LIBERTY Long-Term Extension study (identifier: NCT03412890), in which all women received once-daily, open-label relugolix combination therapy. The primary endpoint of this subanalysis was the proportion of Black or African American treatment responders: women who achieved a menstrual blood loss volume of 2 g/dL) in hemoglobin levels; and decreased symptom severity and distress because of uterine fibroid-associated symptoms and improvements in health-related quality of life through 52 weeks were demonstrated. The most frequently reported adverse events during the cumulative 52-week treatment period were hot flush (12.9%), headache (5.7%), and hypertension (5.7%). Bone mineral density was preserved through 52 weeks. Once-daily relugolix combination therapy improved uterine fibroid-associated heavy menstrual bleeding in most Black or African American women who participated in the LIBERTY Long-Term Extension study. The safety and efficacy profile of relugolix combination therapy in Black or African American women was consistent with previously published results from the overall study population through 52 weeks. Findings from this subanalysis will assist shared decision-making by helping providers and Black or African American women understand the efficacy and safety of relugolix combination therapy as a pharmacologic option for the management of uterine fibroid-associated symptoms.

The IMproving Primary Screening And Colposcopy Triage trial: human papillomavirus, cervical cytology, and histopathologic results from the baseline and 1-year follow-up phase

An increase in human papillomavirus test volumes is expected in the near future because human papillomavirus-based screening protocols are expected to become more widely adopted. The IMproving Primary Screening And Colposcopy Triage trial, a prospective, multicenter, US-based cervical cancer screening trial, was conducted to obtain US Food and Drug Administration approvals for the new, high-throughput cobas human papillomavirus (cobas HPV) test for use on the cobas 6800/8800 Systems (cobas HPV) for detecting cervical precancerous and cancerous cells (cervical intraepithelial neoplasia of grade 2 or worse and grade 3 or worse). Here, the baseline demographics, human papillomavirus test results, cervical cytology, and histopathologic results are presented. In addition, the baseline and 1-year risks of cervical intraepithelial neoplasia grade 2 or worse and grade 3 or worse associated with the human papillomavirus results are reported. In total, 35,263 women aged between 25 and 65 years undergoing routine screening were enrolled; liquid-based cytology and 2 polymerase chain reaction-based tests for high-risk human papillomavirus were performed. Women with abnormal Papanicolaou cytology, women positive for high-risk human papillomavirus by either of the 2 human papillomavirus tests, and a random subset of women negative according to the Papanicolaou cytology and the 2 human papillomavirus tests were referred for a colposcopy and cervical biopsy. Women who did not meet the study endpoint were eligible for the 1-year follow-up study phase. Verification bias-adjusted cervical disease prevalence and risks and 95% confidence intervals were computed. The prevalence of atypical squamous cells of undetermined significance and worse than atypical squamous cells of undetermined significance cytology were 6.5% and 3.2%, respectively. Prevalence of high-risk human papillomavirus, human papillomavirus 16, and human papillomavirus 18 based on the new cobas HPV test were 15.1%, 3.1%, and 1.4%, respectively. Both cytologic abnormalities and human papillomavirus positivity declined with increasing age. Among women who had a colposcopy and biopsy, the prevalence of cervical intraepithelial neoplasia grade 2 or worse and grade 3 or worse were 8.8% and 3.6%, respectively. The baseline and 1-year cumulative risks for cervical intraepithelial neoplasia grade 3 or worse were 13.6% and 16.9%, respectively, among women who tested positive for human papillomavirus 16. Women who tested negative for human papillomavirus had the lowest 1-year cumulative risk for cervical intraepithelial neoplasia grade 3 or worse (0.06%). The contemporary, age-specific prevalence of human papillomaviruses (including human papillomavirus 16 and 18), cytologic abnormalities, and cervical intraepithelial neoplasia in a large, US-based cervical cancer screening population provides benchmarks for healthcare policies, screening programs, and for laboratories and clinicians.

Eliminating disparities in endometrial cancer: adherence to high-quality care is not enough

Long-term outcome of postmenopausal women with proliferative endometrium on endometrial sampling

Proliferative endometrium has been reported in 15% of endometrial biopsies of women aged 50 years and older. Contrary to endometrial hyperplasia, proliferative endometrium has not been associated with the risk of endometrial cancer. This study aimed to report on the long-term outcome of postmenopausal women who received a diagnosis of proliferative endometrium. This is a retrospective cohort study of 1808 women aged 55 years and older who underwent endometrial sampling between January 1997 and December 2008. Outcome data were available through February 2018. Women with a proliferative endometrium were compared with those with an atrophic endometrium for future development of endometrial hyperplasia or cancer. A subanalysis was performed for those who presented with postmenopausal bleeding. Uni- and multivariable logistic regression analyses were used to assess for confounders. In this study, 297 women (16.4%) received a diagnosis of proliferative endometrium. Furthermore, 962 women met the inclusion criteria. Among those women, 278 had a proliferative endometrium, and 684 had an atrophic endometrium. Women with a proliferative endometrium were younger (61.2 vs 64.5 years; P<.0001) and had a higher body mass index (33.9 vs 30.6 kg/m One of the 6 postmenopausal women who underwent endometrial sampling had a proliferative endometrium. Furthermore, 11.9% of women developed endometrial hyperplasia or cancer, a 4-fold greater incidence than women with an atrophic endometrium. The findings of this study suggest that long-term monitoring is warranted for women with postmenopausal bleeding and a proliferative endometrium histology. Further studies are needed to examine if a treatment is required to negate the risk of unopposed estrogen.

The midlife transition and the risk of cardiovascular disease and cancer Part I: magnitude and mechanisms

Heart disease and cancer are the leading causes of death in the United States. In women, the clinical appearance of both entities-coronary heart disease and cancer (breast, endometrium, and ovary)-escalate during the decades of the midlife transition encompassing the menopause. In addition to the impact of aging, during the interval between the age of 40 and 65 years, the pathophysiologic components of metabolic syndrome also emerge and accelerate. These include visceral adiposity (measured as waist circumference), hypertension, diabetes, and dyslipidemia. Osteoporosis, osteoarthritis, sarcopenia, depression, and even cognitive decline and dementia appear, and most, if not all, are considered functionally related. Two clinical reports confirm the interaction linking the emergence of disease: endometrial cancer and metabolic syndrome. One describes the discovery of unsuspected endometrial cancer in a large series of elective hysterectomies performed in aged and metabolically susceptible populations. The other is from the Women's Health Initiative Observational Study, which found a positive interaction between endometrial cancer and metabolic syndrome regardless of the presence or absence of visceral adiposity. Both provide additional statistical support for the long-suspected causal interaction among the parallel but variable occurrence of these common entities-visceral obesity, heart disease, diabetes, cancer, and the prevalence of metabolic syndrome. Therefore, 2 critical clinical questions require analysis and answers: 1: Why do chronic diseases of adulthood-metabolic, cardiovascular, endocrine-and, in women, cancers of the breast and endometrium (tissues and tumors replete with estrogen receptors) emerge and their incidence trajectories accelerate during the postmenopausal period when little or no endogenous estradiol is available, and yet the therapeutic application of estrogen stimulates their appearance? 2: To what extent should identification of these etiologic driving forces require modification of the gynecologist's responsibilities in the care of our patients in the postreproductive decades of the female life cycle? Part l of this 2-part set of "expert reviews" defines the dimensions, gravity, and interactive synergy of each clinical challenge gynecologists face while caring for their midlife (primarily postmenopausal) patients. It describes the clinically identifiable, potentially treatable, pathogenic mechanisms driving these threats to quality of life and longevity. Part 2 (accepted, American Journal of Obstetrics & Gynecology) identifies 7 objectives of successful clinical care, offers "triage" prioritization targets, and provides feasible opportunities for insertion of primary preventive care initiatives. To implement these goals, a reprogrammed, repurposed office visit is described.

Risk assessment of endometrial cancer and endometrial intraepithelial neoplasia in women with abnormal bleeding and implications for clinical management algorithms

Most endometrial cancer cases are preceded by abnormal uterine bleeding, offering a potential opportunity for early detection and cure of endometrial cancer. Although clinical guidelines exist for diagnostic workup of abnormal uterine bleeding, consensus is lacking regarding optimal management for women with abnormal bleeding to diagnose endometrial cancer. We report the baseline data from a prospective clinical cohort study of women referred for endometrial evaluation at the Mayo Clinic, designed to evaluate risk stratification in women at increased risk for endometrial cancer. Here, we introduce a risk-based approach to evaluate diagnostic tests and clinical management algorithms in a population of women with abnormal bleeding undergoing endometrial evaluation at the Mayo Clinic. A total of 1163 women aged ≥45 years were enrolled from February 2013 to May 2019. We evaluated baseline absolute risks and 95% confidence intervals of endometrial cancer and endometrial intraepithelial neoplasia according to clinical algorithms for diagnostic workup of women with postmenopausal bleeding (assessment of initial vs recurrent bleeding episode and endometrial thickness measured through transvaginal ultrasound). We also evaluated risks among women with postmenopausal bleeding according to baseline age (4 mm. We assessed the clinical efficiency of each strategy by estimating the percentage of women who would be referred for endometrial biopsy, the percentage of cases detected and missed, and the ratio of biopsies per case detected. Among the 593 women with postmenopausal bleeding, 18 (3.0%) had endometrial intraepithelial neoplasia, and 47 (7.9%) had endometrial cancer, and among the 570 premenopausal women with abnormal bleeding, 8 (1.4%) had endometrial intraepithelial neoplasia, and 7 (1.2%) had endometrial cancer. Maximum risk was noted in women aged 60+ years (17.7%; 13.0%-22.3%), followed by those with recurrent bleeding (14.7%; 11.0%-18.3%). Among women with an initial bleeding episode for whom transvaginal ultrasound was recommended, endometrial thickness did not provide meaningful risk stratification: risks of endometrial cancer and endometrial intraepithelial neoplasia were nearly identical in women with an endometrial thickness of >4 mm (5.8%; 1.3%-10.3%) and ≤4 mm (3.6%; 0.9%-8.6%). In contrast, among those aged 4 mm, the risk of endometrial cancer and endometrial intraepithelial neoplasia was 8.4% (4.3%-12.5%), and in those with an endometrial thickness of ≤4 mm, the risk was 0% (0.0%-3.0%; P=.01). The most efficient strategy was to perform biopsy in all women aged 60+ years and among those aged 4 mm, with the lowest percentage referred to biopsy while still detecting all cases. Existing clinical recommendations for endometrial cancer detection in women with abnormal bleeding are not consistent with the underlying risk. Endometrial cancer risk factors such as age can provide important risk stratification compared with the assessment of recurrent bleeding. Future research will include a formal assessment of clinical and epidemiologic risk prediction models in our study population as well as validation of our findings in other populations.

Black and Hispanic women are less likely than white women to receive guideline-concordant endometrial cancer treatment

Differences in receipt of guideline-concordant treatment might underlie well-established racial disparities in endometrial cancer mortality. Using the National Cancer Database, we assessed the hypothesis that among women with endometrioid endometrial cancer, racial/ethnic minority women would have lower odds of receiving guideline-concordant treatment than white women. In addition, we hypothesized that lack of guideline-concordant treatment was linked with worse survival. We defined receipt of guideline-concordant treatment using the National Comprehensive Cancer Network guidelines. Multivariable logistic regression models were used to compute odds ratios and 95% confidence intervals for associations between race and guideline-concordant treatment. We used multivariable Cox proportional hazards regression models to estimate hazards ratios and 95% confidence intervals for relationships between guideline-concordant treatment and overall survival in the overall study population and stratified by race/ethnicity. This analysis was restricted to the 89,319 women diagnosed with an invasive, endometrioid endometrial cancer between 2004 and 2014. Overall, 74.7% of the cohort received guideline-concordant treatment (n = 66,699). Analyses stratified by race showed that 75.3% of non-Hispanic white (n = 57,442), 70.1% of non-Hispanic black (n = 4334), 71.0% of Hispanic (n = 3263), and 72.5% of Asian/Pacific Islander patients (n = 1660) received treatment in concordance with guidelines. In multivariable-adjusted models, non-Hispanic black (odds ratio, 0.92, 95% confidence interval, 0.86-0.98) and Hispanic women (odds ratio, 0.90, 95% confidence internal, 0.83-0.97) had lower odds of receiving guideline-concordant treatment compared with non-Hispanic white women, while Asian/Pacific Islander women had a higher odds of receiving guideline-concordant treatment (odds ratio, 1.11, 95% confidence interval, 1.00-1.23). Lack of guideline-concordant treatment was associated with lower overall survival in the overall study population (hazard ratio, 1.12, 95% confidence interval, 1.08-1.15) but was not significantly associated with overall survival among non-Hispanic black (hazard ratio, 1.09, 95% confidence interval, 0.98-1.21), Hispanic (hazard ratio, 0.92, 95% confidence interval=0.78-1.09), or Asian/Pacific Islander (hazard ratio, 0.90, 95% confidence interval, 0.70-1.16) women. Non-Hispanic black and Hispanic women were less likely than non-Hispanic white women to receive guideline-concordant treatment, while Asian/Pacific Islander women more commonly received treatment in line with guidelines. Furthermore, in the overall study population, overall survival was worse among those not receiving guideline-concordant treatment, although low power may have had an impact on the race-stratified models. Future studies should evaluate reasons underlying disparate endometrial cancer treatment.

Differential expression of receptor activator of nuclear factor kappa B in healthy endometrium, ovarian endometrioma, and endometrioid ovarian cancer

Impact of breast cancer history on decision-making for ovarian cancer risk-reducing surgery in the TUBA-WISP-II study

Female BRCA1/2 pathogenic variant carriers have an increased risk of breast and ovarian cancer. In the TUBA-WISP II study, women chose between standard risk-reducing salpingo-oophorectomy and risk-reducing salpingectomy with delayed oophorectomy to prevent ovarian cancer. At inclusion, a substantial proportion of the enrolled women had a history of breast cancer, which could affect decision-making. This study aimed to describe decision-making regarding the type and timing of risk-reducing surgery between women with and without a history of breast cancer. Premenopausal BRCA1/2 pathogenic variant carriers completed Web-based questionnaires on their personal histories and preferred risk-reducing strategy. Differences in the type and timing of the first risk-reducing surgery between women with and without a history of breast cancer were assessed. A multivariate analysis was performed to examine personal, environmental, and breast cancer-related characteristics associated with the choice of risk-reducing salpingo-oophorectomy among women with a history of breast cancer. This study included 1676 women, among whom 222 (13.2%) had a history of breast cancer. Of note, 77.0% of women with a history of breast cancer chose risk-reducing salpingectomy with delayed oophorectomy compared with 78.0% of women without a history of breast cancer (P=.73). Individuals with breast cancer before their BRCA1/2 diagnosis had their first surgery at a median of 2 years later than those who were diagnosed simultaneously or had their BRCA1/2 diagnosis first. Women diagnosed with breast cancer within the guideline age range for completing risk-reducing salpingo-oophorectomy (35-40 years for BRCA1 and 40-45 years for BRCA2) more often chose risk-reducing salpingo-oophorectomy than those before the guideline age range (odds ratio, 6.2 [95% confidence interval, 1.9-19.9]). A history of breast cancer was not associated with a preference for a specific risk-reducing strategy. Women diagnosed with breast cancer within the guideline age range more often chose risk-reducing salpingo-oophorectomy than those diagnosed with breast cancer before the guideline age range.

Evaluating the trend of time to colposcopy follow-up among women with a positive primary human papillomavirus screening result at Kaiser Permanente Southern California

Timeliness of colposcopy follow-up after primary human papillomavirus screening has not been well examined. We evaluated time to colposcopy follow-up among women with an abnormal primary human papillomavirus screening result overall and by human papillomavirus genotype, triage cytology results, race/ethnicity, and neighborhood deprivation index. Women aged 30 to 65 years who received primary human papillomavirus screening at Kaiser Permanente Southern California from July 15, 2020, to December 31, 2021 and had screening results that required colposcopy follow-up were identified. All data were collected from Kaiser Permanente Southern California's electronic medical records. Multivariable modified Poisson models were used to evaluate the associations between human papillomavirus type and triage cytology results, race/ethnicity, neighborhood deprivation index, and receiving a colposcopy within 3 months and 6 months of screening results. A total of 5833 women were included. The mean age was 42.9 years; 11.4%, 9.8%, 48.7%, and 24.4% were of Asian/Pacific Islander, non-Hispanic Black, Hispanic, and non-Hispanic White race/ethnicity. Overall, 71% and 78% received colposcopy within 3 and 6 months of screening, respectively. Compared with women with non-16/18, other high-risk human papillomavirus types and low-grade cytology results, women with HPV 16/18 with normal low-grade or high-grade cytology results and women with other high-risk human papillomavirus and high-grade cytology results were more likely to have colposcopy within 3 months of screening results [risk ratio ranged from 1.21 (95% confidence interval, 1.16-1.25) to 1.34 (95% confidence interval, 1.25, 1.42)]. Non-Hispanic Black women (vs non-Hispanic White, risk ratio=0.93 [0.87, 1.00]) and women from the most deprived neighborhoods (vs least deprived, risk ratio=0.95 [0.90, 1.00]) had lower likelihoods of receiving colposcopy within 3 months of screening. Findings for 6 months of follow-up were similar to that of 3 months. Our observations confirmed prioritization of diagnostic follow-up for women with human papillomavirus 16/18+ as well as high-grade cytology results. Barriers to incomplete colposcopy follow-up and disparity should be better understood and addressed.

Racial and ethnic enrollment disparities in clinical trials leading to Food and Drug Administration approvals for gynecologic malignancies

Compared to White women, Black women and other minority groups have a higher age-adjusted incidence risk of cervical and endometrial cancer. However, the extent of racial and ethnic disparities in clinical trial enrollment among studies performed mainly in North America and Europe for gynecologic malignancy is unknown. This study analyzed enrollment rates by race/ethnicity in trials that led to Food and Drug Administration approvals for gynecological cancers from 2010 to 2024. This cross-sectional study examined clinical trials registered with ClinicalTrials.gov that resulted in new Food and Drug Administration approvals for gynecologic malignancies between 2010 and 2024. Exclusion criteria were studies not conducted in North America or Europe. Enrollment fractions were obtained by dividing the number of trial participants segregated by the racial/ethnic group by the corresponding U.S. cancer prevalence (uterine, ovarian, and cervical cancer) for 2016 to 2020 for each racial/ethnic group. Odds ratios and 95% confidence intervals were calculated to compare enrollment fractions of minority groups to non-Hispanic Whites. A total of 31 studies met the inclusion criteria, with 21 reporting race/ethnicity data. Three (3/21) studies dichotomized race as non-Hispanic White and non-White and 7 (7/21) reported ethnicity. The median number of participants was 494 [interquartile range 150-674]. Fifteen studies were phase III, and 6 were phase IB/II trials. Treatments included immune checkpoint inhibitors (7 studies), poly (ADP-ribose) polymerase inhibitors (5), vascular endothelial growth factor inhibitors (4), antibody-drug conjugates (4), and an imaging marker (1). Across all studies, 11,258 patients were included, 5563 (49.4%) in ovarian cancer studies, 2963 (26.3%) in endometrial cancer studies, and 2732 (24.3%) in cervical cancer studies. Three studies (n=1734) dichotomized participants into non-Hispanic White and non-White; non-Hispanic White 1291 [74.4%] and non-White 443 [25.6%], and enrollment fractions were 0.51% for non-Hispanic White and 0.43% for no-White, with non-White being underrepresented odds ratio 0.85, 95% confidence interval [0.76-0.95], P=.004. In an Analysis of 18 studies reporting race categories, non-Hispanic Black patients were significantly underrepresented (odds ratio 0.50, 95% confidence interval [0.45-0.54], P<.001), while Asian patients were overrepresented (odds ratio 2.81, 95% confidence interval [2.64-2.99], P<.001). In the 4 studies reporting ethnicity, Hispanic patients were also significantly underrepresented (odds ratio 0.69, 95% confidence interval [0.61-0.78], P<.001). In clinical trials, performed in North America and Europe mainly, leading to Food and Drug Administration approvals for gynecologic malignancies, non-Hispanic Black and Hispanic patients are significantly underrepresented compared to non-Hispanic White participants when enrollment is benchmarked to the U.S. female population with gynecological cancer. These trials do not adequately reflect the U.S. populations diagnosed with these malignancies. Enrollment strategies to increase diversity are urgently needed to ensure clinical trial results are equitable and applicable across all populations. Efforts from the American Society of Clinical Oncology, the Association of Community Cancer Centers, and the Gynecologic Oncologic Group/Society of Gynecologic Oncology Inclusion, Diversity, Equity, and Access initiative provide a comprehensive framework for achieving this goal.

Patient-reported quality of life might depend on prophylactic or therapeutic surgery for women with higher genetic predisposition to breast or ovarian cancer

Survival outcomes of primary vs interval cytoreductive surgery for International Federation of Gynecology and Obstetrics stage IV ovarian cancer: a nationwide population-based target trial emulation

The effect of primary cytoreductive surgery vs interval cytoreductive surgery on International Federation of Gynecology and Obstetrics stage IV ovarian cancer outcomes remains uncertain and may vary depending on the stage and the location of extraperitoneal metastasis. Emulating target trials through causal assessment, combined with propensity score adjustment, has become a leading method for evaluating interventions using observational data. This study aimed to assess the effect of primary vs interval cytoreductive surgery on progression-free and overall survival in patients with International Federation of Gynecology and Obstetrics stage IV ovarian cancer using target trial emulation. Using the comprehensive French national health insurance database, we emulated a target trial to explore the causal impacts of primary vs interval cytoreductive surgery on stage IV ovarian cancer prognosis (Surgery for Ovarian cancer FIGO 4: SOFI-4). The clone method with inverse probability of censoring weighting was used to adjust for informative censoring and to balance baseline characteristics between the groups. Subgroup analyses were conducted based on the stages and extraperitoneal metastasis locations. The study included patients younger than 75 years of age, in good health condition, who were diagnosed with stage IV ovarian cancer between January 1, 2014, and December 31, 2022. The primary and secondary outcomes were respectively 5-year progression-free survival and 7-year overall survival. Among the 2772 patients included in the study, 948 (34.2%) were classified as having stage IVA ovarian cancer and 1824 (65.8%) were classified as having stage IVB ovarian cancer at inclusion. Primary cytoreductive surgery was performed for 1182 patients (42.6%), whereas interval cytoreductive surgery was conducted for 1590 patients (57.4%). The median progression-free survival for primary cytoreductive surgery was 19.7 months (interquartile range, 19.3-20.1) as opposed to 15.7 months (interquartile range, 15.7-16.1) for those who underwent interval cytoreductive surgery. The median overall survival was 63.1 months (interquartile range, 61.7-65.4) for primary cytoreductive surgery in comparison with 55.6 months (interquartile range, 53.8-56.3) for interval cytoreductive surgery. The findings of our study indicate that primary cytoreductive surgery is associated with a 5.0-month increase in the 5-year progression-free survival (95% confidence interval, 3.8-6.2) and a 3.9-month increase in 7-year overall survival (95% confidence interval, 1.9-6.2). These survival benefits of primary over interval cytoreductive surgery were observed in both the International Federation of Gynecology and Obstetrics stage IVA and IVB subgroups. Primary cytoreductive surgery demonstrated improved progression-free survival and overall survival in patients with pleural, supradiaphragmatic, or extra-abdominal lymph node metastasis. This study advocates for the benefits of primary cytoreductive surgery over interval cytoreductive surgery for patients with stage IV ovarian cancer and suggests that extraperitoneal metastases like supradiaphragmatic or extra-abdominal lymph nodes should not automatically preclude primary cytoreductive surgery consideration in suitable patients.

Multiomic analysis of uterine leiomyomas in self-described Black and White women: molecular insights into health disparities

Black women are at an increased risk of developing uterine leiomyomas and experiencing worse disease prognosis than White women. Epidemiologic and molecular factors have been identified as underlying these disparities, but there remains a paucity of deep, multiomic analysis investigating molecular differences in uterine leiomyomas from Black and White patients. To identify molecular alterations within uterine leiomyoma tissues correlating with patient race by multiomic analyses of uterine leiomyomas collected from cohorts of Black and White women. We performed multiomic analysis of uterine leiomyomas from Black (42) and White (47) women undergoing hysterectomy for symptomatic uterine leiomyomata. In addition, our analysis included the application of orthogonal methods to evaluate fibroid biomechanical properties, such as second harmonic generation microscopy, uniaxial compression testing, and shear-wave ultrasonography analyses. We found a greater proportion of MED12 mutant uterine leiomyomas from Black women (>35% increase; Mann-Whitney U, P<.001). MED12 mutant tumors exhibited an elevated abundance of extracellular matrix proteins, including several collagen isoforms, involved in the regulation of the core matrisome. Histologic analysis of tissue fibrosis using trichrome staining and secondary harmonic generation microscopy confirmed that MED12 mutant tumors are more fibrotic than MED12 wild-type tumors. Using shear-wave ultrasonography in a prospectively collected cohort, Black patients had fibroids that were firmer than White patients, even when similar in size. In addition, these analyses uncovered ancestry-linked expression quantitative trait loci with altered allele frequencies in African and European populations correlating with differential abundance of several proteins in uterine leiomyomas independently of MED12 mutation status, including tetratricopeptide repeat protein 38. Our study shows that Black women have a higher prevalence of uterine leiomyomas harboring mutations in MED12 and that this mutational status correlates with increased tissue fibrosis compared with wild-type uterine leiomyomas. Our study provides insights into molecular alterations correlating with racial disparities in uterine leiomyomas and improves our understanding of the molecular etiology underlying uterine leiomyoma development within these populations.

Altered extracellular matrix–related pathways accelerate the transition from normal to prefibroid myometrium in Black women

Black women experience a disproportionate impact of uterine fibroids compared to White women, including earlier diagnosis, higher frequency, and more severe symptoms. The etiology underlying this racial disparity remains elusive. The aim of this study was to evaluate the molecular differences in normal myometrium (fibroid-free uteri) and at-risk myometrium (fibroid-containing uteri) tissues in Black and White women. We conducted whole-genome RNA-seq on normal and at-risk myometrium tissues obtained from both self-identified Black and White women (not Hispanic or Latino) to determine global gene expression profiles and to conduct enriched pathway analyses (n=3 per group). We initially assessed the differences within the same type of tissue (normal or at-risk myometrium) between races. Subsequently, we analyzed the transcriptome of normal myometrium compared to at-risk myometrium in each race and determined the differences between them. We validated our findings through real-time PCR (sample size range=5-12), western blot (sample size range=5-6), and immunohistochemistry techniques (sample size range=9-16). The transcriptomic analysis revealed distinct profiles between Black and White women in normal and at-risk myometrium tissues. Interestingly, genes and pathways related to extracellular matrix and mechanosensing were more enriched in normal myometrium from Black than White women. Transcription factor enrichment analysis detected greater activity of the serum response transcription factor positional motif in normal myometrium from Black compared to White women. Furthermore, we observed increased expression levels of myocardin-related transcription factor-serum response factor and the serum response factor in the same comparison. In addition, we noted increased expression of both mRNA and protein levels of vinculin, a target gene of the serum response factor, in normal myometrium tissues from Black women as compared to White women. Importantly, the transcriptomic profile of normal to at-risk myometrium conversion differs between Black and White women. Specifically, we observed that extracellular matrix-related pathways are involved in the transition from normal to at-risk myometrium and that these processes are exacerbated in Black women. We found increased levels of Tenascin C, type I collagen alpha 1 chain, fibronectin, and phospho-p38 MAPK (Thr180/Tyr182, active) protein levels in at-risk over normal myometrium tissues from Black women, whereas such differences were not observed in samples from White women. These findings indicate that the racial disparities in uterine fibroids may be attributed to heightened production of extracellular matrix in the myometrium in Black women, even before the tumors appear. Future research is needed to understand early life determinants of the observed racial differences.

Robotic-assisted versus conventional laparoscopic surgery for endometrial cancer: long-term results of a randomized controlled trial

Robotic-assisted laparoscopy has become a widely and increasingly used modality of minimally invasive surgery in the treatment of endometrial cancer. Due to its technical advantages, robotic-assisted laparoscopic surgery offers benefits, such as a lower rate of conversions compared to conventional laparoscopy. Yet, data on long-term oncological outcomes after robotic-assisted laparoscopy is scarce and based on retrospective cohort studies only. This study aimed to assess overall survival, progression-free survival, and long-term surgical complications in patients with endometrial cancer randomly assigned to robotic-assisted or conventional laparoscopy. This randomized controlled trial was conducted at the Department of Gynecology and Obstetrics of Tampere University Hospital, Finland. Between 2010 and 2013, 101 patients with low-grade endometrial cancer scheduled for minimally invasive surgery were randomized preoperatively 1:1 either to robotic-assisted or conventional laparoscopy. All patients underwent laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy. A total of 97 patients (49 in the robotic-assisted laparoscopy group and 48 in the conventional laparoscopy group) were followed up for a minimum of 10 years. Survival was analyzed using Kaplan-Meier curves, log-rank test, and Cox proportional hazard models. Binary logistic regression analysis was used to analyze risk factors for trocar site hernia. In the multivariable regression analysis, overall survival was favorable in the robotic-assisted group (hazard ratio 0.39; 95% confidence interval [CI], 0.15-0.99, P=.047) compared to the conventional laparoscopy group. There was no difference in progression-free survival (log-rank test, P=.598). The 3-, 5-, and 10-year overall survival were 98.0% (95% CI, 94.0-100) vs 97.9% (93.8-100), 91.8% (84.2-99.4) vs 93.7% (86.8-100), and 75.5% (64.5-87.5) vs 85.4% (75.4-95.4) for the conventional laparoscopy and the robotic-assisted groups, respectively. Trocar site hernia developed more often for the robotic-assisted group compared to the conventional laparoscopy group 18.2% vs 4.1% (odds ratio 5.42, 95% CI, 1.11-26.59, P=.028). The incidence of lymphocele, lymphedema, or other long-term complications did not differ between the groups. The results of this randomized controlled trial suggest a minor overall survival benefit in endometrial cancer after robotic-assisted laparoscopy compared to conventional laparoscopy. Hence, the use of robotic-assisted technique in the treatment of endometrial cancer seems safe, though larger randomized controlled trials are needed to confirm any potential survival benefit. No alarming safety signals were detected in the robotic-assisted group since the rate of long-term complications differed only in the incidence of trocar site hernia.

Less radical surgery for early-stage cervical cancer: a systematic review

A systematic review was performed to examine the outcomes of simple hysterectomy for women with low-risk, early-stage cervical cancer. MEDLINE, Embase, Web of Science, and ClinicalTrials.gov were searched from inception until November 4, 2020. Original research reporting recurrence or survival outcomes among women with early-stage cervical cancer (defined as stage IA2 to IB1 disease) who were treated with simple hysterectomy. Data regarding study characteristics, tumor characteristics, other treatment modalities, adjuvant therapy, recurrence, and survival outcomes were analyzed. Studies that reported both simple hysterectomy and radical hysterectomy outcomes were compared in a subgroup analysis. Summary statistics were reported and eligible studies were further analyzed to determine an estimated hazard ratio comparing simple hysterectomy with radical hysterectomy. A total of 21 studies were included, of which 3 were randomized control trials, 14 retrospective studies, 2 prospective studies, and 2 population-level data sets. The cohort included 2662 women who underwent simple hysterectomy, of which 36.1% had stage IA2 disease and 61.0% stage IB1 disease. Most cases (96.8%) involved tumors of ≤2 cm in size, and 15.4% of cases were lymphovascular space invasion positive. Approximately 71.8% of women who underwent simple hysterectomy had a lymph node assessment, and 30.7% of women underwent adjuvant chemotherapy or radiation. The most common complications described were lymphedema (24%), lymphocysts (22%), and urinary incontinence (18.5%). The total death rate for studies that reported deaths was 5.5%. By stage, there was a 2.7% mortality rate among IA2 disease and a 7.3% mortality rate among IB1 disease. Of note, 18 studies reported outcomes for both simple and radical hysterectomy, with a 4.5% death rate in the radical hysterectomy group and a 5.8% death rate in the simple hysterectomy group. Estimated and reported hazard ratio demonstrated no significant association for mortality between radical and nonradical surgeries for IA2 disease but potentially increased risk of mortality among IB1 disease. All studies had a moderate to high risk of bias, including the 3 randomized control trials. Level of evidence was limited to III to IV. The use of less radical surgery for women with stage IA2 and small volume IB1 cervical cancers appears favorable. However, there is concern that simple hysterectomy in women with stage IB1 tumors may adversely impact survival. Overall, the quality of studies available is modest, limiting the conclusions that can be drawn from the available literature.

Risk of endometrial cancer after insufficient endometrial biopsy: a retrospective cohort study

Endometrial biopsies are used to diagnose abnormalities in the endometrium, but the biopsies are sometimes insufficient. To evaluate the risk of detecting endometrial cancer in individuals with an insufficient endometrial index biopsy compared to individuals with a normal index biopsy. In this retrospective cohort study, we used the Danish Pathology Register to identify individuals with endometrial biopsies between 2013 and 2017. We categorized initial and follow-up samples as normal, insufficient, hyperplastic, or cancer by using Systematized Nomenclature of Medicine codes. We had 4 years of follow-up until December 31, 2021, and we compared categories with Kaplan-Meier analysis, a log-rank test, and Cox regression. A total of 80,761 Danish individuals were included. Of these, 13,964 (17.3%) had an insufficient endometrial index biopsy, meaning the index sample contained too little tissue for a definitive diagnosis. From this group, 6130 (43.9%) individuals had a follow-up endometrial biopsy performed. Unadjusted for age (hazard ratio, 3.7; 95% confidence interval, 3.56-3.84), the incidence of endometrial cancer (n=368; 2.6%) was higher in individuals with an insufficient index biopsy compared to those with a normal index biopsy (n=423; 0.7%). However, when we adjusted for age, the hazard for endometrial cancer was only slightly higher after an insufficient biopsy compared to a normal biopsy (hazard ratio, 1.16; 95% confidence interval, 1.02-1.31). We found an increased risk of detecting endometrial cancer in individuals with an insufficient index biopsy compared to individuals with a normal index biopsy. After adjusting for age, the risk was only slightly increased.

Enhancing colposcopy training using a widely accessible digital education tool in China

Colposcopy is a cornerstone of cervical cancer prevention; however, there is a global shortage of colposcopists. It is challenging to train a sufficient number of colposcopists through in-person methods, which hinders our ability to adequately diagnose and manage positive cases. A digital platform is needed to make colposcopy training more efficient, scalable, and sustainable; however, current online training programs are generally based on didactic curricula that do not incorporate image analysis training. In addition, long-term assessments of online training are not readily available. Therefore, innovative digital training and an assessment of its effectiveness are needed. This study aimed to evaluate the short- and long-term effects of DECO (an online Digital Education Tool for Colposcopy) on trainees' colposcopy competencies and confidence. DECO can be used both on laptops and smartphones and comprises 4 training modules (image interpretation; terminology learning; video teaching; and collection of guidelines and typical cases) and 2 test modules. DECO was tested through a pre-post study between September and November 2022. Participants were recruited in China, and DECO training lasted 12 days. Trainees initially learned basic theory before completing training using 200 image-based cases. Pretest, posttest, and follow-up testing included 20 distinct image-based questions, and was conducted on Days 0, 13, and 60. Primary outcomes were competence and confidence scores. Secondary measures were response distributions for colposcopic diagnoses, biopsies, and DECO training satisfaction. Multilevel modeling was used to determine improvement from baseline to posttraining and follow-up for the outcomes of interest. Among 402 participants recruited, 96.8% (n=389) completed pretesting, 84.1% (n=338) posttesting, and 75.1% (n=302) follow-up testing. Colposcopic competence and confidence increased across this study. Diagnostic scores improved on average from 55.3 (53.7-56.9) to 70.4 (68.9-71.9). The diagnostic accuracy for normal/benign lesions, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or worse increased by 16.9%, 13.1%, and 16.9%, respectively. Mean confidence scores increased from 48.1 (45.6-50.6) to 56.2 (54.5-57.9). These improvements remained evident 2 months after training. Trainees were also satisfied with DECO overall. Most found DECO to be scientific (82.5%), easy to use (75.2%), and clinically useful (98.4%), and would recommend it to colleagues (93.2%). DECO is a useful, acceptable digital education tool that improves colposcopy competencies and confidence. DECO could make colposcopy training more efficient, scalable, and sustainable because there are no geographic or time limitations. Therefore, DECO could be used to alleviate the shortage of trained colposcopists around the world.

Ovarian sex cord-stromal cell tumors and the risk of sex hormone-sensitive cancers

Sex cord-stromal cell tumors are rare ovarian tumors. Some sex cord-stromal cell tumors secrete hormones that originate from the ovarian sex or stromal cells. Previous studies have indicated an increased risk for breast and endometrial cancers. However, these studies focused only on the sex cord-stromal cell tumor-subtype of adult granulosa cell tumors, and the estimates stemmed from selected cohorts and lacked a well-described cohort, making it difficult to adjust for possible confounders. We examined the incidence of other primary hormone-sensitive cancers and compared their risk with that in a matched cohort of women without sex cord-stromal cell tumors. This nested cohort study evaluated women diagnosed with sex cord-stromal cell tumors. We established a cohort of women diagnosed with sex cord-stromal cell tumors using Systematized Medical Nomenclature for Medicine codes from the Danish Pathology Register. Sex cord-stromal cell tumors diagnoses were considered valid if the primary diagnosis was established at a tertiary referral center or confirmed by at least 2 pathologists. A 1:10 matched control group matched by birth year was selected from national registries. Variables for the follow-up of cases and controls were drawn from national registries and included assessment of the rates of breast, ovarian, and endometrial cancer, hormone use, Charlson Comorbidity Index, and sociodemographics. Hazard ratios for cancer rates were calculated using multivariate Cox proportional hazards models with sex cord-stromal cell tumor exposure estimated in early and delayed models to capture cancer rates over time. The standardized incidence ratios for very rare sex cord-stromal cell tumors were determined using a log-linear Poisson model. Among the 1516 tumors with Systematized Medical Nomenclature for Medicine codes for sex cord-stromal cell tumors, 1387 met the inclusion criteria after pathologic chart review. The majority had benign tumors, primarily thecoma or fibrothecomas (66%), and 26% had adult granulosa cell tumors. Increased rates of breast cancer were found among patients with thecomas (hazard ratio, 1.2; 95% confidence interval, 1.0-1.4). In the analysis of all sex cord-stromal cell tumors combined, an increased rate of synchronous endometrial cancer was found (hazard ratio, 3.3; 95% confidence interval, 2.7-4.1). In the subgroup analysis, malignant and benign sex cord-stromal cell tumors showed significantly higher hazard ratios for synchronous endometrial cancer, notably adult granulosa cell tumors (hazard ratio, 10.7; 95% confidence interval, 5.7-20.1). In the model that assessed the rates of endometrial cancer 2 months after surgical removal of the sex cord-stromal cell tumor, no increased rates were found. Sertoli cell tumors were associated with an increased incidence of breast cancer (standardized incidence ratio, 18.9; 95% confidence interval, 2.7-134). Both Sertoli and Leydig cell tumors were associated with a higher incidence of synchronous endometrial cancer with standardized incidence ratios of 41.4 (95% confidence interval, 10.4-166) and 44.9 (95% confidence interval, 18.7-108), respectively. Women with sex cord-stromal cell tumors have an increased rate of synchronous endometrial cancer, and women with benign sex cord-stromal cell tumors have an increased rate of synchronous ovarian cancer. A marginally increased rate of breast cancer has been observed in women with thecomas. There was no increase in the rate of breast cancer among women with adult granulosa cell tumors. It is recommended that women diagnosed with hormone-secreting sex cord-stromal cell tumors and additional risk factors for endometrial cancer (abnormal uterine bleeding and/or abnormal endometrial thickness) should undergo an endometrial biopsy to assess for the presence of cancer.

Intrauterine manipulator during hysterectomy for endometrial cancer: a systematic review and meta-analysis of oncologic outcomes

This study aimed to assess the effects on oncologic outcomes of intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer. A systematic literature search was performed by an expert librarian in multiple electronic databases from inception to January 31, 2023. We included all studies in the English language that compared oncologic outcomes (recurrence-free, cause-specific, or overall survival) between endometrial cancer patients who underwent total laparoscopic or robotic hysterectomy for endometrial cancer with vs without the use of an intrauterine manipulator. Studies comparing only peritoneal cytology status or lymphovascular space invasion were summarized for completeness. No selection criteria were applied to the study design. Four reviewers independently reviewed studies for inclusion, assessed their risk of bias, and extracted data. Pooled hazard ratios with 95% confidence intervals were estimated for oncologic outcomes using the random effect model. Heterogeneity was quantified using the I Out of 350 identified references, we included 2 randomized controlled trials and 12 observational studies for a total of 14 studies and 5,019 patients. The use of an intrauterine manipulator during hysterectomy for endometrial cancer was associated with a pooled hazard ratio for recurrence of 1.52 (95% confidence interval, 0.99-2.33; P=.05; I Intrauterine manipulator use during hysterectomy for endometrial cancer was neither significantly associated with recurrence-free and overall survival nor with positive peritoneal cytology or lymphovascular space invasion, but further prospective studies are needed.

Impact of the coronavirus disease 2019 pandemic on the quality of life for women with ovarian cancer

The coronavirus disease 2019 pandemic has resulted in unprecedented challenges for the oncology community. For people living with cancer, treatments are interrupted, surgeries cancelled, and regular oncology evaluations rescheduled. People with cancer and their physicians must balance plausible fears of coronavirus disease 2019 and cancer treatment with the consequences of delaying cancer care. We aim to evaluate the experience of women with ovarian cancer during the coronavirus disease 2019 pandemic. Women with a current or previous diagnosis of ovarian cancer completed an online survey focusing on treatment interruptions and quality of life. The quality of life was measured with the Cancer Worry Scale and Hospital Anxiety and Depression Scale. The survey was distributed through survivor networks and social media. Univariate and multivariable linear regression analysis were used to evaluate the effect of participant characteristics on quality of life survey scores. A total of 603 women, from 41 states, visited the survey website between March 30, 2020, and April 13, 2020, and 555 (92.0%) completed the survey. The median age was 58 years (range, 20-85). At the time of survey completion, 217 participants (43.3%) were in active treatment. A total of 175 participants (33%) experienced a delay in some component of their cancer care. Ten (26.3%) of the 38 participants scheduled for surgery experienced a delay, as did 18 (8.3%) of the 217 participants scheduled for nonsurgical cancer treatment. A total of 133 participants (24.0%) had a delayed physician appointment, 84 (15.1%) laboratory tests, and 53 (9.6%) cancer-related imaging. Among the cohort, 88.6% (489) reported significant cancer worry, 51.4% (285) borderline or abnormal anxiety, and 26.5% (147) borderline or abnormal depression. On univariate analysis, age less than 65 years, being scheduled for cancer treatment or cancer surgery, delay in oncology care, being self-described as immunocompromised, and use of telemedicine were all associated with higher levels of cancer worry. Higher anxiety scores were associated with age less than 65 years and being self-described as immunocompromised. Higher depression scores were associated with age less than 65 years, being scheduled for cancer surgery, delay in oncology care, being self-described as immunocompromised, and use of telemedicine. On multivariable linear regression analysis, age less than 65 and being self-described as immunocompromised were independently predictive of greater cancer worry, anxiety, and depression, and delay in cancer care was predictive of anxiety and depression. The coronavirus disease 2019 crisis is affecting care of patients with ovarian cancer; surgeries, treatments, scheduled physician appointments, laboratory tests, and imaging are cancelled or delayed. Younger age, presumed immunocompromise, and delay in cancer care were associated with significantly higher levels of cancer worry, anxiety, and depression. Providers must work with patients to balance competing risks of coronavirus disease 2019 and cancer, recognizing that communication is a critical clinical tool to improve quality of life in these times.

Disparities in clinical drug trial participation in endometrial cancer: a real-world analysis

Racial disparities in clinical trial participation for uterine cancer have been reported. We sought to examine disparities of endometrial cancer patient participation in clinical drug trials in a contemporary, real-world population in the United States. We conducted a retrospective cohort study of patients with advanced or recurrent patients with endometrial cancer diagnosed from 2013 to 2021 using a real-world electronic health record-derived database representing approximately 800 academic and community practice sites across the United States. We used multilevel Poisson regression modeling to analyze the association of clinical drug trial participation with patient, sociodemographic, health system, and cancer factors. Of 4423 patients with endometrial cancer, 2807 (63.5%) identified as white, 649 (14.7%) Black, 78 (1.8%) Asian, and 964 (21.8%) some other race. Overall, 3.8% of patients with endometrial cancer ever participated in a clinical drug trial. High-risk histology and residence in the Southeast were associated with increased clinical trial participation (risk ratio (RR) 2.28, 95% confidence interval (CI) 1.12-4.62 and RR 2.59, 95% CI 1.26-5.3 respectively). By race, trial participants included 123 (72.4%) White, 18 (10.6%) Black, 1 (0.59%) Asian, and 28 (16.4%) some other race. While Black patients had the greatest proportion of high-risk histology, they were 50.0% less likely than white patients to participate in a clinical trial (RR 0.50, 95% CI 0.30-0.83). Black patients with endometrial cancer were disproportionately underrepresented in clinical drug trials, despite having higher rates of aggressive cancer histologies. Efforts to increase diversity in endometrial cancer clinical trial participants are needed.

Longitudinal effects of adjuvant chemotherapy and lymph node staging on patient-reported outcomes in endometrial cancer survivors: a prospective cohort study

Most patients with endometrial cancer with localized disease are effectively treated and survive for a long time. The primary treatment is hysterectomy, to which surgical staging procedures may be added to assess the need for adjuvant therapy. Longitudinal data on patient-reported outcomes comparing different levels of primary treatment are lacking, especially when adjuvant radiotherapy is omitted. We assessed the impact of lymphadenectomy and adjuvant chemotherapy on patient-reported symptoms, function, and quality of life. We hypothesized that these treatment modalities would substantially affect patient-reported outcomes at follow-up. We prospectively included patients with endometrial cancer enrolled in the ongoing MoMaTEC2 study (ClinicalTrials.gov Identifier: NCT02543710). Patients were asked to complete the patient-reported outcome questionnaires European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire EN24 preoperatively and at 1 and 2 years of follow-up. Functional domains and symptoms were analyzed for the whole cohort and by treatment received. To assess the effect of the individual treatment modifications, we used mixed regression models. Baseline data were available for 448 patients. Of these patients, 339 and 219 had reached 1-year follow-up and 2-year follow-up, respectively. Treatment included hysterectomy (plus bilateral salpingo-oophorectomy) alone (n=177), hysterectomy and lymph node staging without adjuvant therapy (n=133), or adjuvant chemotherapy irrespective of staging procedure (n=138). Overall, patients reported improved global health status and quality of life (+9 units; P<.001), increased emotional and social functioning, and increased sexual interest and activity (P<.001 for all) from baseline to year 1, and these outcomes remained stable at year 2. Means of functional scales and quality of life were similar to age- and sex-weighted reference cohorts. Mean tingling and numbness and lymphedema increased after treatment. The group who received adjuvant chemotherapy had a larger mean reduction in physical functioning (-6 vs +2; P=.002) at year 1, more neuropathy (+30 vs +5; P<.001; year 1) at years 1 and 2, and more lymphedema at year 1 (+11 vs +2; P=.007) than the group treated with hysterectomy and salpingo-oophorectomy only. In patients not receiving adjuvant chemotherapy, patient-reported outcomes were similar regardless of lymph node staging procedures. Adjuvant chemotherapy independently increased fatigue, lymphedema, and neuropathy in mixed regression models. Patients with endometrial cancer receiving adjuvant chemotherapy reported significantly reduced functioning and more symptoms up to 2 years after treatment. For patients treated by surgery alone, surgical staging did not seem to affect the quality of life or symptoms to a measurable degree at follow-up. Therefore, subjecting patients to lymph node removal to tailor adjuvant therapy seems justified from the patient's viewpoint; however, efforts should increase to find alternatives to traditional chemotherapy.

New horizons of sentinel lymph node technique in early ovarian cancer

Fragmentation of postoperative care after surgical management of ovarian cancer at 30 days and 90 days

Fragmentation of care, wherein a patient is discharged from an index hospital and undergoes an unexpected readmission to a nonindex hospital, is associated with increased risk of adverse outcomes. Fragmentation has not been well-characterized in ovarian cancer. The objective of this study was to assess risk factors and outcomes that are associated with fragmentation of care among women who undergo surgical treatment of ovarian cancer. The Nationwide Readmission Database was used to identify all-cause 30-day and 90-day postoperative readmissions after surgical management of ovarian cancer from 2010-2014. Postoperative fragmentation was defined as readmission to a hospital other than the index hospital of the initial surgery. Multivariable regression analyses were used to identify predictors of fragmentation in both 30-day and 90-day readmissions. Similarly, multivariable models were developed to determine the association between fragmentation and death among women who were readmitted. A total of 10,445 patients (13.3%) were readmitted at 30 days, and 14,124 patients (18.0%) were readmitted at 90 days. Of these, there was a 20.8% and 25.7% rate of postoperative care fragmentation for 30-day and 90-day readmissions, respectively. Patient risk factors that were associated with fragmented postoperative care included Medicare insurance, lower income quartiles, and nonroutine discharge to facility. Hospital factors that were associated with decreased risk of fragmentation included operation at a metropolitan teaching hospital and performance of extended procedures. Cost and length of stay for the readmission were similar among those who had fragmented and nonfragmented readmissions at both 30 and 90 days. Although there was no association between death and fragmentation for patients who were readmitted within 30 days (odds ratio, 1.19; 95% confidence interval, 0.93-1.51), patients who had a fragmented readmission at 90 days were 22% more likely to die than those who were readmitted at 90 days to their index hospital (odds ratio, 1.22; 95% confidence interval, 1.00-1.49). Fragmentation of care is common in women with ovarian cancer who require postoperative readmission. Fragmented postoperative care is associated with an increased risk of death among women who are readmitted within 90 days of surgery.

Chemotherapy alone for patients 75 years and older with epithelial ovarian cancer—is interval cytoreductive surgery still needed?

Patients ≥75 years old with ovarian cancer experience high perioperative morbidity, but recruitment into prospective trials to assess the role of surgery continues to be challenging. To compare overall survival for patients ≥75 years old with ovarian cancer after chemotherapy alone vs neoadjuvant chemotherapy with interval cytoreductive surgery. Data were extracted from the National Cancer Data Base from 2004 to 2014. Kaplan-Meier and Cox proportional hazards models were used for statistical analyses. Of 1661 patients (median age: 79 years), most were white (88%) and had stage III-IV disease (95%), and 51% had serous histology. Of those who did not receive primary surgery, 58% had chemotherapy alone and the remainder had neoadjuvant chemotherapy with interval cytoreductive surgery. The use of neoadjuvant chemotherapy with interval cytoreductive surgery increased from 28% to 50% in years 2004-2007 to 2012-2014 (P<.001). Compared with neoadjuvant chemotherapy with interval cytoreductive surgery, chemotherapy-only patients were older (80 vs 78 years; P<.001) and had more advanced stage disease (98% vs 91%; P<.001). The 5-year overall survival of the entire study group was 14%; those who underwent neoadjuvant chemotherapy with interval cytoreductive surgery had overall survival of 25% compared with only 7% in chemotherapy alone group (P<.001). In multivariable analysis, neoadjuvant chemotherapy with interval cytoreductive surgery (hazard ratio, 0.44; 95% confidence interval, 0.36-0.54; P<.001) was an independent predictor for improved survival. Older (80-84 years) age (hazard ratio, 1.35; 95% confidence interval, 1.12-1.63; P=.002), advanced (stage III-IV) disease (hazard ratio; 2.06, 95% confidence interval, 1.37-3.09; P=.001), and clear cell histology (hazard ratio; 2.17, 95% confidence interval, 1.10-4.28; P=.03) portended for worse outcome. Patients ≥75 years with ovarian cancer old have an overall poor prognosis. Receiving neoadjuvant chemotherapy followed by interval cytoreductive surgery is associated with greater overall survival compared to chemotherapy alone.

Cervical cancer risk and screening among women seeking assistance with basic needs

In the United States, more than half of cervical cancers occur in women who are inadequately screened. Interventions to improve access to cervical cancer preventive care is critical to reduce health inequities. This study aimed to evaluate the need for cervical cancer screening among women seeking assistance with basic needs and to assess best approaches to facilitate Papanicolaou test referral. This study is a secondary analysis of a randomized controlled trial of low-income female callers to 2-1-1 Missouri, a helpline for local health and social services. The need for cervical cancer screening was assessed. Callers were randomized to 1 of 3 arms, each providing a Papanicolaou test referral: verbal referral only, verbal referral and tailored print reminder, or verbal referral and navigator. The primary outcome was contacting a Papanicolaou test referral 1 month following intervention. Student t tests or Mann-Whitney U tests were used to analyze significant differences in continuous variables, whereas Fisher exact or χ Among 932 female callers, 250 (26.8%) needed cervical cancer screening. The frequency of unmet basic needs was high, the most common being lack of money for unexpected expenses (91.2%) and necessities, such as food, shelter, and clothing (73.2%). Among those needing a Papanicolaou test, 211 women received screening referrals. Women in the navigator group (21 of 71, 29.6%) reported higher rates of contacting a Papanicolaou test referral than those exposed to verbal referral only (11/73, 15.1%) or verbal referral and tailored print reminder (9/67, 13.4%) (P=.03). Among 176 women with ≥2 unmet needs who received a Papanicolaou test referral, the provision of a navigator remained associated with contacting the referral (navigator [33.9%] vs verbal referral [17.2%] vs tailored reminder [10.2%]; P=.005). Assignment to the navigator group (adjusted odds ratio, 3.4; 95% confidence interval, 1.4-8.5) and nonwhite race (adjusted odds ratio, 2.0; 95% confidence interval, 1.5-2.8) were independent predictors of contacting a Papanicolaou test referral. Low-income women seeking assistance with basic needs often lack cervical cancer screening. Health navigators triple the likelihood that women will make contact with Papanicolaou test services, but most 2-1-1 callers still fail to schedule Papanicolaou testing despite assistance from navigators. Interventions beyond health navigators are needed to reduce cervical cancer disparities.

Analysis of risk factors for recurrence in cervical cancer patients after fertility-sparing treatment: The FERTIlity Sparing Surgery retrospective multicenter study

Fertility-sparing treatment in patients with cervical cancer should, in principle, follow identical algorithms to that in patients without future reproductive plans. In recent years, a trend toward nonradical procedures, such as conization or simple trachelectomy, has become apparent in medical literature, because of their associations with better pregnancy outcomes. However, the published reports included small numbers of patients and heterogenous treatment strategies to ascertain the safety of such approaches. This study aimed to collect multi-institutional data regarding the oncological outcomes after fertility-sparing treatment in patients with cervical cancer and to identify prognostic risk factors, including the influence of the radicality of individual cervical procedures. Patients aged 18 to 40 years with International Federation of Gynecology and Obstetrics 2018 stage IA1 with positive lymphovascular space invasion or ≥IA2 cervical cancer who underwent any type of fertility-sparing procedure were eligible for this retrospective observational study, regardless of their histotype, tumor grade, and history of neoadjuvant chemotherapy. Associations between disease- and treatment-related characteristics with the risk of recurrence were analyzed. A total of 733 patients from 44 institutions across 13 countries were included in this study. Almost half of the patients had stage IB1 cervical cancer (49%), and two-thirds of patients were nulliparous (66%). After a median follow-up of 72 months, 51 patients (7%) experienced recurrence, of whom 19 (2.6%) died because of the disease. The most common sites of recurrence were the cervix (53%) and pelvic nodes (22%). The risk of recurrence was 3 times higher in patients with tumors >2 cm in size than in patients with smaller tumors, irrespective of the treatment radicality (19.4% vs 5.7%; hazard ratio, 2.982; 95% confidence interval, 1.383-6.431; P=.005). The recurrence risk in patients with tumors ≤2 cm in size did not differ between patients who underwent radical trachelectomy and patients who underwent nonradical (conization and simple trachelectomy) cervical procedures (P=.957), regardless of tumor size subcategory (2 cm in size.

Performance of ultrasound and rates of guideline-concordant care in a diverse postmenopausal bleeding cohort

Professional society guidelines endorse the use of ultrasound to evaluate an initial episode of postmenopausal bleeding, with endometrial sampling reserved for patients with an endometrial thickness exceeding 4 mm. However, the data supporting this ultrasound-based approach are derived from cohort studies with minimal racial and ethnic diversity. This study aimed to evaluate rates of adequate endometrial visualization, prompt guideline-concordant care, and identify risk factors for lack of timely indicated sampling in a multi-institutional cohort of patients who underwent ultrasound to evaluate postmenopausal bleeding. Patients aged ≥45 years who underwent transvaginal ultrasound for an initial coding-based diagnosis of postmenopausal bleeding were eligible for this retrospective cohort study. Ultrasound findings of the endometrium were classified as thin (endometrium ≤4 mm), thick (endometrium >4 mm), or inadequate (endometrium not completely visualized). Associations between clinicodemographic factors, ultrasound findings, and follow-up patterns were analyzed. We defined care as guideline-concordant if patients with a thin endometrium on the index ultrasound did not undergo biopsy, or if those with a thick or inadequately visualized endometrium received indicated endometrial sampling within 3 months after the index ultrasound. We analyzed outcomes using univariable and multivariable logistic regressions. A total of 3614 patients were included in the study (48.4% non-Hispanic White, 28.5% non-Hispanic Black, 9.6% Hispanic, 3.0% Asian, and 10.4% other/missing). Rates of inadequate ultrasound examination varied between racial/ethnic cohorts (non-Hispanic White 5.9%, non-Hispanic Black 18.8%, Hispanic 12.7%, and Asian 9.2%). Uterine fibroids were present in 71.5% (737/1031) of non-Hispanic Black patients, as opposed to 43.3% (757/1750) of non-Hispanic White patients, and were strongly associated with lower odds of adequate ultrasound (odds ratio, 0.29 [95% confidence interval, 0.23-0.38]; P<.001). Rates of endometrial sampling were 53.5% (209/391) after an inadequate ultrasound and 75.3% (1329/1765) after a thickened endometrium finding. Guideline-concordant care rates were 85.7% for non-Hispanic White (1500/1750), 78.0% for non-Hispanic Black (804/1031), 83.6% for Hispanic (290/347), and 82.7% for other/unknown (402/83) patients. Compared with non-Hispanic White patients, non-Hispanic Black patients were less likely to receive guideline-concordant care (adjusted odds ratio, 0.64 [95% confidence interval, 0.52-0.78]). Non-Hispanic Black patients with postmenopausal bleeding have a higher rate of inadequate ultrasound examination due to fibroids and are less likely to receive prompt guideline-concordant care. An ultrasound-based workup of postmenopausal bleeding risks delays in endometrial cancer diagnoses and may contribute to racial disparities in outcomes. A universal biopsy approach for postmenopausal bleeding may be considered to decrease variation in and improve guideline-concordant care.

Development and validation of a histology-specific natural history model of ovarian cancer

Ovarian cancer is the second leading cause of death from gynecologic cancers, yet no effective screening program exists for the general population. Past screening trials evaluated the effectiveness of annual ovarian cancer screening and concluded that it does not yield substantial mortality reduction. Future investments on ovarian cancer screening trials would require convincing preliminary evidence on the effectiveness of interventions of interest. Simulation modeling is an effective, fast, cost-efficient, and safe approach to gain insights on the effectiveness of interventions, that is increasingly being used to inform guidelines for cancer screening programs. Models that simulate the natural progression of diseases in the absence of any intervention, commonly referred to as natural history models, are the cornerstone of such analyses, because they provide a reference point for evaluating interventions. Currently, no histology-specific natural history model exists for ovarian cancer despite major differences among subtypes. Develop and validate a histology-specific ovarian cancer natural history model. We developed natural history models for the most common histological subtypes of epithelial ovarian cancer: high-grade serous carcinoma, low-grade serous carcinoma, mucinous carcinoma, clear cell carcinoma, endometrioid carcinoma, carcinosarcoma, and not otherwise specified. Each natural history model simulates the natural progression of ovarian cancer from disease's onset until death from any cause. We modeled ovarian cancer progression as a state-transition model comprising of 13 mutually exclusive and collectively exhaustive health states. We informed the model input parameters using observed, nationally representative estimates, whenever possible. Unobserved parameters (eg, preclinical transitions) were estimated through calibration to histology-specific data from the Surveillance, Epidemiology, and End Results registry. We validated the natural history models on the control arms of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and the United Kingdom Collaborative Trial of Ovarian Cancer Screening trials, in terms of ovarian cancer incidence and mortality rates, and stage distribution at diagnosis. Differences between observed and estimated outcomes were assessed using traditional statistical tests. The calibrated natural history models reproduced the observed Surveillance, Epidemiology, and End Results data (range of weighted root mean square error across histological subtypes: 0.0081-0.0185) as well as individual calibration targets; survival after diagnosis, stage distribution at diagnosis, and age distribution at diagnosis (ranges of mean square error across histological subtypes: 0.0029-0.0204, 0.0005-0.0203, and 0.0637-0.0816, respectively). The natural history models reproduced the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial's observed incidence and mortality rates, and stage at diagnosis (P value=.411 for incidence, P value=.195 for mortality, and P value=.200 for stage distribution at diagnosis) and the United Kingdom Collaborative Trial of Ovarian Cancer Screening's observed ovarian cancer incidence (P value=.607) and mortality (P value=.624) rates. The average duration of the preclinical phase ranges between 1 and 3 years, which partly explains screening's failure to yield mortality reduction. Moreover, stage II ovarian cancer, independent of histological subtype, is a transient state characterized by noticeably shorter average duration when compared to stages I, III, and IV. The developed natural history models accurately describe the histology-specific natural progression of ovarian cancer and provide important insights into the natural history of the disease. The models may be used to evaluate the impact of future and emerging ovarian cancer interventions, thus providing valuable information to decision-makers and policymakers.

The art of cold knife conization: a demonstration of technique in live patients and a low-fidelity simulation model

Cervical excision via cold knife conization is recommended for conditions, such as adenocarcinoma in situ or predominantly endocervical high-grade dysplasia. A successful cold knife conization involves visualization, targeting of the pathology, obtaining an unfragmented specimen, and consideration of postexcision endocervical curettage. This article presents a video that demonstrates cold knife conization techniques to facilitate pathologic analysis and a low-fidelity simulation model for learners. The video depicts 2 cold knife conizations in nulliparous patients with (1) high-grade lesion on endocervical curettage and (2) high-grade dysplasia on ectocervical biopsy. In addition, this article demonstrates a low-fidelity simulation model that can be used to familiarize physicians with the conization procedure and essential hemostatic techniques. Although the authors acknowledge the limitations of the model to include lack of bleeding, corresponding patient cases demonstrate essential hemostatic techniques. Using standard surgical instruments, cold knife conization was performed for both patients, allowing for the excision of an appropriately sized intact specimen. Differences in technical approach when excising the ectocervix vs the endocervix were detailed. Endocervical curettage was performed after specimen removal, and the tissue bed was made hemostatic. Both conizations were performed without complication, and negative margins were achieved. In the simulation model, easily obtainable supplies, including small cups, balloons, cling wrap, cotton balls, and hot dogs, were used to create an imitation cervix. This can allow for demonstration and practice with suture placement, excision of an intact specimen, and hemostatic techniques. Using proper technique for adequate cold knife conization specimens facilitates pathologic analysis of dysplasia, cancer, and margin status. Negative margins have a substantial effect on recurrence and the need for future cervical procedures, which may affect future obstetrical outcomes. Low-fidelity simulation models can provide accessible avenues for technical familiarization and training in this procedure.

Uptake and patient-related outcomes of mainstreaming genetic testing: a systematic review and meta-analysis

Mainstreaming genetic testing refers to genetic testing for cancer susceptibility genes following cancer diagnosis, which is provided by nongenetic health professionals of the cancer-treating team. Mainstreaming can be used to guide cancer treatment and secondary cancer prevention in the patient and to identify carriers in the family members of patients who test positive through cascade testing. We aimed to assess uptake and patient-reported outcomes of mainstreaming genetic testing. We searched PubMed and the Cochrane Library from inception to June 2024. Our population included adult patients offered mainstreaming genetic testing (intervention). Outcomes included testing uptake, satisfaction, decisional conflict/regret, anxiety, depression, and cancer-related distress. We followed a prospective protocol according to Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines (International Prospective Register of Systematic Reviews: CRD42023467312). Qualitative synthesis and random effects meta-analyses were performed. Quality assessment was performed using the Methodological Index for Non-Randomized Studies. Searches yielded 5314 studies; 29 studies (n=13,219) were included, of which 14 were on ovarian cancer (n=6039), 6 on breast cancer (n=4354), 3 on prostate cancer (n=772), 1 on endometrial cancer (n=302), and 5 on multiple cancers (n=1752). There were no studies for colorectal cancer. Pooled genetic testing uptake was 91% (95% confidence interval=86-96, I Mainstreaming genetic testing uptake is associated with high uptake and satisfaction and low decision conflict, regret, and post-test distress. Quality and quantity of evidence across different types of cancers vary significantly.

Cervical function in pregnancy and disease: new insights from single-cell analysis

The uterine cervix plays an essential role in regulating fertility, maintaining pregnancy, remodeling in preparation for parturition, and protecting the reproductive tract from infection. A compromise in cervical function contributes to adverse clinical outcomes. Understanding molecular events that drive the multifunctional and temporally defined roles of the cervix is necessary to effectively treat infertility, reproductive tract infections, preterm birth, labor dystocia, and cervical cancer. The application of single-cell technologies to study cervical pathophysiology, while in its infancy, underscores the potential of these approaches in developing clinically relevant biomarkers of disease and preventative therapies. This review focuses on insights gained from single-cell transcriptomic studies in human and mouse cervical tissue and highlights outstanding questions in the field. One collective advance from single-cell analysis is the dynamic plasticity of cervical epithelial cells during the reproductive cycle in health and disease. Single-cell comparisons between upper and lower regions of the reproductive tract also highlight the distinct and divergent immunological responses elicited in the cervix during the reproductive lifespan. These findings may reconcile prior controversies in the role of proinflammatory mediators during parturition. In addition to providing obstetric insights, single-cell technologies elucidate the molecular pathways that drive cervical cancer progression. Thus far, these technologies have uncovered cellular heterogeneity in the tumor microenvironment and have identified potential cancer stem cells. While single-cell technology alone will not uncover all the molecular underpinnings contributing to preterm birth or cervical cancer, the insights derived from this valuable technology will accelerate our understanding of cervical biology in health and disease, which ultimately will help develop biomarkers for disease prediction and prevention therapies.

Facilitators and barriers to acceptability of a biopsy-first approach in the diagnostic evaluation for endometrial cancer among Black women

Black people in the United States with endometrial cancer have a 5-year mortality rate that is more than twice that of White patients. This disparity is driven, in part, by Black individuals' higher likelihood of advanced-stage diagnosis. Transvaginal ultrasound-as a triage tool for referral to tissue sampling-underperforms among Black women. In this context, tissue sampling as an early step for symptomatic Black patients may improve timely diagnosis of endometrial cancer. Patient acceptability of biopsy as a priority test is necessary to ensure success of this clinical approach. Yet, little is known about the perspective of Black women on biopsy in the diagnostic workup for endometrial cancer. The goal of this qualitative study was to identify facilitators and barriers to acceptability of a biopsy-first approach to rule out endometrial cancer among cisgender Black women. In this community-engaged qualitative study, 3 focus groups were conducted among cisgender Black women at risk for endometrial cancer. Convenience sampling was carried out using social media and newsletter networks. A focus group guide was developed based on the theory of planned behavior and contained questions about past experiences, initial impressions of a biopsy-first approach, an educational presentation, and final thoughts about a biopsy-first approach. Transcripts of focus group recordings were coded using a combined inductive and deductive approach and analyzed using directed and thematic content analysis. Twenty-five women participated in focus groups (Table 1), with 6 to 10 participants per group. Participants initially expressed understandable apprehension and rejection of a biopsy-first approach in the context of symptom presentation, informed by concerning past experiences and awareness of medical racism. Yet, by the end of the focus groups, there was overall acceptability of biopsy as a priority test to rule out endometrial cancer. Barriers of biopsy acceptability include negative past experiences, including mismatch of pain expectations with actual experiences, and known incidents of medical racism. Facilitators of biopsy acceptability included fostering patient-provider trust through explicit acknowledgment of medical racism, sharing information, personalized recommendations, and racial concordance in care; and health education about racial disparities in endometrial cancer, the biopsy procedure, physical risks of forgoing biopsy, emotional benefits of biopsy, and the range of possible pain experiences. This qualitative study describes Black cisgender women's perspectives on biopsy as a first-line approach in evaluating abnormal bleeding to rule out endometrial cancer in this population. We find that a patient-centered communication approach that incorporates trust-building, shared decision-making, and education may be most successful when recommending biopsy. These findings can inform culturally competent clinical guideline development and public health education to improve timely diagnosis-and ultimately survival-of endometrial cancer among Black women.

Short-term outcomes of minimally invasive total vs supracervical hysterectomy for uterine fibroids: a National Surgical Quality Improvement Program study

Uterine fibroids are the most common indication for benign hysterectomy in the United States, but data regarding the association between hysterectomy type and outcomes for this indication are lacking. This study aimed to describe the rate and odds of short-term (30 days) postoperative complications between patients who underwent minimally invasive total laparoscopic hysterectomy and those who underwent laparoscopic supracervical hysterectomy for uterine fibroids. This was a cohort study of prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. The characteristics of women who underwent total laparoscopic hysterectomy and those who underwent laparoscopic supracervical hysterectomy for uterine fibroids were identified. In addition, the risk factors associated with the occurrence of 30-day postoperative complications, defined according to the Clavien-Dindo classification, were identified. Multivariate regression analysis, including age, body mass index, race, comorbidities, American Society of Anesthesiologists classification, uterine weight, and concomitant procedures, was performed to identify the adjusted odds of postoperative complications. The co-primary outcomes were (1) the risk of a composite of any postoperative complications and (2) the risk of major postoperative complications according to surgical type. Overall, 44,413 patients underwent minimally invasive total laparoscopic hysterectomy, and 6383 patients underwent laparoscopic supracervical hysterectomy. The operative time was shorter in the total laparoscopic hysterectomy group than in the laparoscopic supracervical hysterectomy group (143.0 vs 150.6 minutes, respectively; P 250 g was lower in the total laparoscopic hysterectomy group than in the laparoscopic supracervical hysterectomy group (39.4% vs 45.1%, respectively; P < .001). The rates of any and major complications were higher in the total laparoscopic hysterectomy group than in the laparoscopic supracervical hysterectomy group (any complications: 6.6% vs 5.3%, respectively; P < .001; major complications: 2.7% vs 1.6%, respectively; P < .001), whereas the rates of minor complications were comparable in both groups (4.4% vs 4.1%, respectively; P = .309). In multivariate regression analysis, laparoscopic supracervical hysterectomy was independently associated with a lower risk of any (adjusted odds ratio, 0.79; 95% confidence interval, 0.70-0.88) and major (adjusted odds ratio, 0.55; 95% confidence interval, 0.44-0.69) complications than total laparoscopic hysterectomy. Laparoscopic supracervical hysterectomy was associated with a lower risk of short-term postoperative complications in patients with uterine fibroids than total laparoscopic hysterectomy. Our findings can aid in shared decision-making before minimally invasive hysterectomy for uterine fibroids.

Cervical cancer disparities in stage at presentation for disaggregated Asian Americans, Native Hawaiians, and Pacific Islanders

Over 20 million people in the United States identified as Asian American, Native Hawaiian, or Pacific Islander in 2022. Despite the diversity of immigration histories, lived experiences, and health needs within the Asian American, Native Hawaiian, or Pacific Islander community, prior studies in cervical cancer have considered this group in aggregate. We sought to analyze disparities in cervical cancer stage at presentation in the United States, focusing on disaggregated Asian American, Native Hawaiian, or Pacific Islander groups. Data from the United States National Cancer Database from 2004 to 2020 of 122,926 patients newly diagnosed with cervical cancer were retrospectively analyzed. Asian American, Native Hawaiian, or Pacific Islander patients were disaggregated by country of origin. Logistic regression, adjusted for clinical and sociodemographic factors, was used to calculate adjusted odds ratios. Higher adjusted odds ratios indicate an increased likelihood of metastatic versus nonmetastatic disease at diagnosis. Out of 122,926 patients with cervical cancer, 5142 (4.2%) identified as Asian American, Native Hawaiian, or Pacific Islander. Compared to non-Hispanic White patients, pooled Asian American, Native Hawaiian, or Pacific Islander patients presented at lower stages of cancer (non-Hispanic White: 58.7% diagnosed local/regional, Asian American, Native Hawaiian, or Pacific Islander : 85.6% at local/regional, χ2 P<.001). The largest Asian American, Native Hawaiian, or Pacific Islander subgroups included Filipino Americans (n=1051, 20.4% of Asian American, Native Hawaiian, or Pacific Islander), Chinese Americans (n=995, 19.4%), Asian Indian/Pakistani Americans (n=711, 13.8%), Vietnamese Americans (n=627, 12.2%), and Korean Americans (n=550, 10.7%) respectively. Asian American, Native Hawaiian, or Pacific Islander disaggregation revealed that Pacific Islander American patients had higher odds of presenting with metastatic disease (adjusted odds ratio 1.58, 95% confidence interval 1.21-2.06, P=.001) relative to non-Hispanic White patients. Conversely, Chinese American (adjusted odds ratio 0.47, 95% confidence interval 0.37-0.59, P<.001), Vietnamese American (adjusted odds ratio 0.54, 95% confidence interval 0.41-0.70, P<.001), Hmong American (adjusted odds ratio 0.46, 95% confidence interval 0.22-0.97, P=.040), and Indian/Pakistani American (adjusted odds ratio 0.76, 95% confidence interval 0.61-0.94, P=.013) patients were less likely to present with metastatic disease. Compared to the largest Asian American, Native Hawaiian, or Pacific Islander group (Chinese American), 9 other subgroups were more likely to present with metastatic disease. The largest differences were observed in Pacific Islander American (adjusted odds ratio 3.44, 95% confidence interval 2.41-4.91, P<.001), Thai American (adjusted odds ratio 2.79, 95% confidence interval 1.41-5.53, P=.003), Kampuchean American (adjusted odds ratio 2.39, 95% confidence interval 1.29-4.42, P=.006), Native Hawaiian American (adjusted odds ratio 2.23, 95% confidence interval 1.37-3.63, P=.001), and Laotian American (adjusted odds ratio 2.02, 95% confidence interval 1.13-3.61, P=.017). In contrast, Vietnamese American (adjusted odds ratio 1.20, 95% confidence interval 0.85-1.71, P=.303), and Hmong American (adjusted odds ratio 1.09, 95% confidence interval 0.50-2.37, P=.828) patients did not show a statistically significant difference in presenting with metastatic disease compared to Chinese American patients. Aggregated evaluation of the Asian American, Native Hawaiian, or Pacific Islander monolith masks disparities in outcomes for distinct populations at risk for equity gaps. This disaggregation study shows that marginalized groups within the larger Asian American, Native Hawaiian, or Pacific Islander population-including Pacific Islander American and Thai American patients-may face different exposures and larger structural barriers to cancer screening and early-stage diagnosis. A future focus on community-based disaggregated research and tailored interventions is necessary to close these gaps.

Prevalence of and risk factors for endometrial polyps among asymptomatic postmenopausal women with uterovaginal prolapse

The prevalence of endometrial polyps among asymptomatic, postmenopausal women is not well defined. There is no clear clinical consensus on how to manage endometrial polyps in this population and whether these polyps truly are a cause for clinical concern. This study aimed to estimate the prevalence of endometrial polyps among asymptomatic (without bleeding), postmenopausal women and to evaluate risk factors associated with their presence. This cross-sectional study assessed the prevalence of endometrial polyps among asymptomatic, postmenopausal women who underwent a hysterectomy for uterovaginal prolapse. Patients were excluded if they underwent a hysterectomy for other indications, including postmenopausal bleeding. Following chart review, eligible patients who received care at a single site in Washington state from 2009 to 2018 were included. The primary outcome was the presence of endometrial polyps on pathology. Risk factors associated with polyp prevalence were subsequently assessed using univariate analysis and multivariate regression. Of the 317 eligible women identified, endometrial polyps were identified in 106 women (33.4%). The average polyp size and endometrial thickness was 13±10 mm and 1.4±1.5 mm, respectively. Most cases (78%) had solitary polyps. Premalignant and malignant lesions were found in 2 cases (1.89%); 1 had endometrial carcinoma and 1 had endometrial intraepithelial neoplasia. Baseline clinical and demographic characteristics were similar between patients with and those without endometrial polyps, including the presence of fibroids, endometriosis, and adenomyosis. A multivariate logistic regression showed that the presence of polyps was independently associated with a high body mass index (odds ratio, 1.06; 95% confidence interval, 1.01-1.12; P=.02) and use of menopausal hormone therapy (odds ratio, 1.67; 95% confidence interval, 1.02-2.72; P=.04). Asymptomatic postmenopausal women who underwent hysterectomy for uterovaginal prolapse exhibited a high prevalence of endometrial polyps. Those who used menopausal hormone therapy and who had a high body mass index were at a higher risk for developing endometrial polyps. Although the risk for malignancy seems to be low, more investigation is warranted to truly quantify the lifetime risk. For now, expectant management may be a reasonable approach for incidentally found, asymptomatic polyps.

The fibroid crisis in Black women: more work to be done!

Prediction of nonresectability using the updated Predictive Index value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study

A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of nonresectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). The aim was to demonstrate the noninferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI)/MRI) in predicting nonresectable tumor (defined as residual disease >1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of nonresectability at ultrasound, CT, WB-DWI/MRI, and surgical exploration. Ultrasound and CT were mandatory index tests, while WB-DWI/MRI was an optional test (non-available in all centers). The predictors of nonresectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV >8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in 6 predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease >1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting nonresectability was reported. Concordance between index tests at the detection of disease at 6 predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa. The study was between 2018 and 2022 in 5 European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1 cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was>1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out, and 50/80 underwent laparoscopy only, because cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of 3 imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and nonresectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI, and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) than CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. Ultrasound showed noninferiority to CT and to WB-DWI/MRI in discriminating between resectable and nonresectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict nonresectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

Characteristics associated with blood transfusion among women undergoing laparoscopic myomectomy: a National Surgical Quality Improvement Program study

Uterine fibroids are the most common benign tumors that affect females. A laparoscopic myomectomy is the standard surgical treatment for most women who wish to retain their uterus. The most common complication of a myomectomy is excessive bleeding. However, risk factors for hemorrhage during a laparoscopic myomectomy are not well studied and no risk stratification tool specific for identifying the need for a blood transfusion during a laparoscopic myomectomy currently exists in the literature. This study aimed to identify risk factors for intraoperative and postoperative blood transfusion during laparoscopic myomectomies and to develop a risk stratification tool to determine the risk for requiring a blood transfusion. This was a retrospective cohort study of the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. Women who underwent a laparoscopic (conventional or robotic) myomectomy were included. Women who received 1 or more blood transfusions within 72 hours after the start time of a laparoscopic myomectomy were compared with those who did not require a blood transfusion. A multivariable analysis was performed to identify risk factors independently associated with the risk for transfusion. Two risk stratification tools to determine the need for a blood transfusion were developed based on the multivariable results, namely (1) based on preoperative factors and (2) based on preoperative and intraoperative factors. During the study period, 11,498 women underwent a laparoscopic myomectomy. Of these, 331(2.9%) required a transfusion. In a multivariable regression analysis of the preoperative factors, Black or African American and Asian races, Hispanic ethnicity, bleeding disorders, American Society of Anesthesiologists class III or IV classification, and a preoperative hematocrit value ≤35.0% were independently associated with the risk for transfusion. Identified intraoperative factors included specimen weight >250 g or ≥5 intramural myomas and an operation time of ≥197 minutes. A risk stratification tool was developed in which points are assigned based on the identified risk factors. The mean probability of transfusion can be calculated based on the sum of the points. We identified preoperative and intraoperative independent risk factors for a blood transfusion among women who underwent a laparoscopic myomectomy. A risk stratification tool to determine the risk for requiring a blood transfusion was developed based on the identified risk factors. Further studies are needed to validate this tool.

Fertility-sparing surgery vs standard surgery for early-stage cervical cancer: difference in 5-year life expectancy by tumor size

Cervical cancer incidence among premenopausal women is rising, and fertility-sparing surgery serves as an important option for this young population. There is a lack of evidence on what tumor size cutoff should be used to define candidacy for fertility-sparing surgery. We sought to describe how the association between fertility-sparing surgery (compared with standard surgery) and life expectancy varies by tumor size among patients with cervical cancers measuring ≤4 cm in largest diameter. Our secondary objective was to quantify the probability of undergoing adjuvant radiotherapy among patients who underwent fertility-sparing surgery as a function of tumor size. We identified patients in the National Cancer Database aged ≤45 years, diagnosed with stage I cervical cancer with tumors ≤4 cm between 2006 and 2018, who received no preoperative radiation or chemotherapy, and who underwent either fertility-sparing surgery (cone or trachelectomy, either simple or radical) or standard surgery (simple or radical hysterectomy) as their primary treatment. Propensity-score matching was performed to compare patients who underwent fertility-sparing surgery with those who underwent standard surgery. A flexible parametric model was employed to quantify the difference in life expectancy within 5 years of diagnosis (restricted mean survival time) based on tumor size among patients who underwent fertility-sparing and those who underwent standard surgery. In addition, among those who underwent fertility-sparing surgery, a logistic regression model was used to explore the relationship between tumor size and the probability of receiving adjuvant radiation. A total of 11,946 patients met the inclusion criteria of whom 904 (7.6%) underwent fertility-sparing surgery. After propensity-score matching, 897 patients who underwent fertility-sparing surgery were matched 1:1 with those who underwent standard surgery. Although the 5-year life expectancy was similar among patients who had fertility sparing surgery and those who had standard surgery regardless of tumor sizes, the estimates of life-expectancy differences associated with fertility-sparing surgery were more precise among patients with smaller tumors (1-cm tumor: restricted mean survival time difference, -0.10 months; 95% confidence interval, -0.67 to 0.47) than among those with larger tumors (4-cm tumor: restricted mean survival time difference, -0.11 months; 95% confidence interval, -3.79 to 3.57). The probability of receiving adjuvant radiation increased with tumor size, ranging from 5.6% (95% confidence interval, 3.9-7.9) for a 1-cm tumor to 37% (95% confidence interval, 24.3-51.8) for a 4-cm tumor. Within 5 years of diagnosis, young patients with stage I cancers measuring ≤4 cm had similar survival outcomes after either fertility-sparing surgery or standard surgery. However, because few patients with tumors >2 cm underwent fertility-sparing surgery, a clinically important survival difference could not be excluded in this population.

Uterine artery embolization vs myomectomy for the management of women with uterine leiomyomas: a systematic review and meta-analysis

This study aimed to investigate whether uterine artery embolization offers a better quality of life than myomectomy in premenopausal women diagnosed with leiomyomas of the uterus. A literature search was performed using the electronic databases of PubMed and Cochrane Central Register of Controlled Trials from inception to January 2023. Randomized controlled trials comparing uterine artery embolization with myomectomy in women of premenopausal age suffering from uterine leiomyomas were considered. The primary outcome was quality of life. The secondary outcomes were reintervention rate and timing, successful pregnancy, stillbirth and miscarriage, cesarean delivery on delivery, and perioperative morbidity. Moreover, time-to-event and standard pairwise meta-analyses were performed, as appropriate. The certainty of the evidence was assessed in line with the Grading of Recommendations, Assessment, Development, and Evaluations methodology. A total of 6 randomized controlled trials met our inclusion criteria. The meta-analysis suggested little to no difference in terms of quality of life between uterine artery embolization and myomectomy (standard mean difference, 0.05; 95% confidence interval, -0.38 to 0.48; I Uterine artery embolization is likely associated with increased reintervention rates and less time to reintervention compared with myomectomy in premenopausal women diagnosed with uterine leiomyomas. Evidence suggests no difference between the 2 interventions regarding perioperative morbidity. Uterine artery embolization may exert no effect on quality of life and successful pregnancy; however, the evidence is very uncertain.

Risk of placenta accreta spectrum following myomectomy: a nationwide cohort study

Whether myomectomy increases the risk of placenta accreta spectrum in the following pregnancies remains controversial. This study aimed to investigate the effect of myomectomy on the risk of placenta accreta spectrum in the following pregnancies. Moreover, different methods of myomectomy on the risk of placenta accreta spectrum were explored. A nationwide cohort study was conducted using data from the Taiwan National Health Insurance Research Database, including all pregnant patients in Taiwan who gave birth between January 2008 and December 2017. A 1:1 propensity score estimation matching was performed for the analysis of myomectomy on the risk of placenta accreta spectrum. Among pregnant patients who received myomectomy, different methods of myomectomy on the risk of placenta accreta spectrum were compared with the control group. Among the 1,371,458 pregnant patients in this study, 11,255 pregnant patients had a history of myomectomy. The risk of placenta accreta spectrum was higher in pregnant patients with a history of myomectomy than in pregnant patients without a history of myomectomy (incidence: 0.96% vs 0.20%; adjusted odds ratio, 2.28; 95% confidence interval, 1.85-2.81; P<.01). Among pregnant patients with a history of myomectomy, 5045 (46.87%) received laparotomic myomectomy, 3973 (36.93%) received laparoscopic myomectomy, and 1742 (16.20%) received hysteroscopic myomectomy. The incidence of placenta accreta spectrum was higher in the hysteroscopic group than in the laparotomic group or the laparoscopic group (1.89% [hysteroscopic group] vs 0.71% [laparotomic group] and 0.81% [laparoscopic group]; P<.05). Compared with patients without a history of myomectomy, the adjusted odds ratio for placenta accreta spectrum was 3.88 (95% confidence interval, 2.68-5.63; P<.05) in the hysteroscopic group. Myomectomy, especially hysteroscopic myomectomy, is associated with an increased risk of placenta accreta spectrum in the subsequent pregnancy.

Demographic reporting and language exclusion in gynecologic oncology clinical trials

Participation in clinical trials may help mitigate disparate cancer outcomes. Thus, ensuring equitable access to clinical trials is a major priority for national cancer organizations. This study aimed to examine clinical trial eligibility criteria that may adversely affect the enrollment of underrepresented groups and assess the availability of demographic information in published gynecologic oncology studies. ClinicalTrials.gov was searched for gynecologic oncology studies conducted between 1997 and 2021. Each study's inclusion and exclusion criteria were reviewed to determine whether demographic factors were used for enrollment screening. For published studies, demographic variables that were reported were identified. The expected clinical trial enrollment based on disease incidence and mortality was compared with the observed trial enrollment based on race. There were 1597 gynecologic oncology studies: 883 (55%) from ovarian cancer studies, 336 (21%) from cervical cancer studies, 262 (17%) from uterine cancer studies, and 116 (7%) from multisite gynecologic oncology studies. Of the 581 published studies, 554 (95%) reported age, 363 (63%) reported race, and 171 (29%) reported ethnicities. Cervical cancer studies were most likely to report demographic information, including race (P=.026) and ethnicity (P<.001). During the study period, 189 studies (12%) excluded patients based on the language spoken. Industry-sponsored trials (odds ratio, 0.07; 95% confidence interval, 0.02-0.30) and organization-sponsored trials (odds ratio, 0.40; 95% confidence interval, 0.22-0.73) were less likely to exclude patients because of language than investigator-initiated trials. A minority of patients (37%) in cervical cancer trials were of White race, compared with 85% of patients in uterine cancer trials and 82% of patients in ovarian cancer trials. Over the last 3 decades, 1 in 10 gynecologic oncology trials excluded patients because of language. Race and ethnicity were reported in more than half of the available studies. Initiatives to increase transparency in recruiting underrepresented patients and reporting demographic data are urgently needed.

Accessory cavitated uterine mass in a multiparous patient with progressive dysmenorrhea

Fatty intrusion in the uterus: a rare case of uterine lipoleiomyoma causing urinary retention

Multiple pregnancy with complete hydatidiform mole and coexisting normal fetus in a retrospective cohort of 141 patients

Multiple pregnancy with a complete hydatidiform mole and a normal fetus is prone to severe obstetrical complications and malignant transformation after birth. Prognostic information is limited for this rare form of gestational trophoblastic disease. This study aimed to determine obstetrical outcomes and the risk of gestational trophoblastic neoplasia in women with multiple pregnancy with complete hydatidiform mole and coexisting normal fetus, and to identify risk factors for poor obstetrical and oncological outcomes to improve patient information and management. This was a retrospective national cohort study of 11,411 records from the French National Center for Trophoblastic Disease registered between January 2001 and January 2022. Among 11,411 molar pregnancies, 141 involved histologically confirmed multiple pregnancy with complete hydatidiform mole and coexisting normal fetus. Roughly a quarter of women (23%; 33/141) decided to terminate pregnancy because of presumed poor prognosis or by choice. Among the 77% of women (108/141) who continued their pregnancy, 16% of pregnancies (17/108) were terminated because of maternal complications, and 37% (40/108) ended in spontaneous miscarriage before 24 weeks' gestation. The median gestational age at delivery in the remaining 47% of pregnancies (51/108) was 32 weeks. The overall neonatal survival rate at day 8 was 36% (39/108; 95% confidence interval, 27-46) after excluding elective pregnancy terminations. Patients with free beta human chorionic gonadotropin levels 10 multiples of the median (odds ratio, 7.0; 95% confidence interval, 1.3-36.5; P=.022). A lower free beta human chorionic gonadotropin level was also associated with better early neonatal survival (the median free beta human chorionic gonadotropin level was 9.4 multiples of the median in patients whose child was alive at day 8 vs 20.0 multiples of the median in those whose child was deceased; P=.02). The overall rate of gestational trophoblastic neoplasia after a multiple pregnancy with complete hydatidiform mole and a normal fetus was 26% (35/136; 95% confidence interval, 19-34). All 35 patients had low-risk International Federation of Gynecology and Obstetrics scores, and the cure rate was 100%. Termination of pregnancy on patient request was not associated with lower risk of gestational trophoblastic neoplasia. Maternal complications such as preeclampsia and postpartum hemorrhage were not associated with higher risk of gestational trophoblastic neoplasia, and neither were high human chorionic gonadotropin levels or newborn survival at day 8. Multiple pregnancy with complete hydatidiform mole and coexisting fetus carries a high risk of obstetrical complications. In patients who continued their pregnancy, approximately one-third of neonates were alive at day 8, and roughly 1 in 4 patients developed gestational trophoblastic neoplasia. Therefore, the risk of malignant transformation appears to be higher compared with singleton complete moles. Low levels of free beta human chorionic gonadotropin may be indicative of better early neonatal survival, and this relationship warrants further study.

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Reply to a question regarding ovarian cancer prevention with partial salpingectomy vs complete

Paradigm shift from tubal ligation to opportunistic salpingectomy at cesarean delivery in the United States

Opportunistic salpingectomy is now recommended at the time of routine gynecologic surgery to reduce the risk of future ovarian cancer, and performance of opportunistic salpingectomy has increased markedly at the time of benign hysterectomy. Salpingectomy has also been suggested to be feasible at the time of cesarean delivery in women desiring sterilization; however, uptake has not been previously studied on a national level. This study aimed to examine recent population trends in the utilization and characteristics of salpingectomy at the time of cesarean delivery in the United States. This is a population-based retrospective observational study querying the National Inpatient Sample between October 2015 and December 2018. The primary outcome measure was the temporal trend of bilateral salpingectomy at cesarean delivery, assessed with linear segmented regression with log transformation utilizing 3-month time increments. The secondary outcome measures included patient characteristics associated with bilateral salpingectomy, assessed with a multinomial regression model, and surgical outcome (hemorrhage, blood transfusion, hysterectomy, and oophorectomy) at the time of bilateral salpingectomy vs bilateral tubal ligation, assessed with generalized estimating equation in a propensity score-matched model. There were 3,813,823 women at the age of 15 to 49 years who had cesarean deliveries included, of whom 397,260 (10.4%) had bilateral salpingectomy and 203,400 (5.3%) had bilateral tubal ligation overall. During the time period studied, performance of bilateral salpingectomy among women undergoing cesarean delivery significantly increased from 4.6% to 13.2% (odds ratio for the fourth quarter of 2018 vs the fourth quarter of 2015, 2.69; 95% confidence interval, 2.63-2.75; Figure panel). In contrast, performance of bilateral tubal ligation among women undergoing cesarean delivery significantly decreased from 11.3% to 2.4% (odds ratio, 0.20; 95% confidence interval, 0.19-0.21). By the third quarter of 2016, the number of women who had bilateral salpingectomy exceeded those who had bilateral tubal ligation at cesarean delivery (8.6% vs 7.3%). Increasing the utilization of bilateral salpingectomy did not vary across age groups; the salpingectomy rate increased from 7.5% to 21.1% among women at the age of ≥35 years and from 3.8% to 10.7% among women at the age of <35 years (both, P<.001). In a propensity score matched model, women in the bilateral salpingectomy group were more likely to have hemorrhage (3.8% vs 3.1%; odds ratio, 1.24; 95% confidence interval, 1.15-1.33), blood product transfusion (2.1% vs 1.8%; odds ratio, 1.16; 95% confidence interval, 1.04-1.30), hysterectomy (0.8% vs 0.4%; odds ratio, 2.28; 95% confidence interval, 1.84-2.82), and oophorectomy (0.3% vs 0.2%; odds ratio, 2.02; 95% confidence interval, 1.47-2.79) than those in the bilateral tubal ligation group. When restricted to the nonhysterectomy cases, the bilateral salpingectomy group had a higher rate of hemorrhage (3.4% vs 3.0%; odds ratio, 1.16; 95% confidence interval, 1.06-1.26) and oophorectomy (0.3% vs 0.1%; odds ratio, 1.75; 95% confidence interval, 1.22-2.50) than the bilateral tubal ligation group. In the United States, the utilization of bilateral salpingectomy at the time of cesarean delivery increased rapidly between 2015 and 2018, replacing tubal ligation as the most common type of sterilization performed with cesarean delivery. The higher surgical morbidity in the bilateral salpingectomy group than the bilateral tubal ligation group observed in this study warrants further investigation.

Uptake and timing of risk-reducing salpingo-oophorectomy among patients with BRCA1 and BRCA2 mutations

In women with BRCA mutations, risk-reducing bilateral salpingo-oophorectomy has been shown to decrease gynecologic cancer-specific and overall mortality. The National Comprehensive Cancer Network recommends that patients with BRCA mutations undergo risk-reducing bilateral salpingo-oophorectomy between the ages of 35 and 40 years for BRCA1 mutation carriers and between the ages of 40 and 45 years for BRCA2 mutation carriers or after childbearing is complete. Currently, uptake and timing of risk-reducing bilateral salpingo-oophorectomy and reasons for delays in risk-reducing bilateral salpingo-oophorectomy are not well understood. We sought to evaluate uptake and timing of risk-reducing bilateral salpingo-oophorectomy among women with BRCA1 and BRCA2 mutations concerning the National Comprehensive Cancer Network guidelines and reasons for delays in risk-reducing bilateral salpingo-oophorectomy. In this retrospective chart review, we identified women with BRCA1 and BRCA2 mutations who discussed risk-reducing bilateral salpingo-oophorectomy with a provider between 2012 and 2021. Uptake of risk-reducing bilateral salpingo-oophorectomy was documented, and patients were classified as having timely or delay in risk-reducing bilateral salpingo-oophorectomy based on the National Comprehensive Cancer Network guidelines. For those with delay in risk-reducing bilateral salpingo-oophorectomy, reasons cited for delay were collected. Comparative statistical analyses were performed to evaluate characteristics of those with timely vs delayed risk-reducing bilateral salpingo-oophorectomy. A multivariable logistic regression model was used to evaluate the associations among factors related to timing of risk-reducing bilateral salpingo-oophorectomy. We identified 638 BRCA1 and BRCA2 mutation carriers seen between 2012 and 2021. Of these patients, 306 (48.0%) had undergone risk-reducing bilateral salpingo-oophorectomy and 332 (52.0%) had not. When evaluating the timing of risk-reducing bilateral salpingo-oophorectomy, 136 (21.3%) underwent timely risk-reducing bilateral salpingo-oophorectomy, 239 (37.5%) had delays in risk-reducing bilateral salpingo-oophorectomy, and 263 (41.2%) had not undergone risk-reducing bilateral salpingo-oophorectomy but were younger than the National Comprehensive Cancer Network age guidelines; therefore, they were neither timely nor delayed. Patients with delay in risk-reducing bilateral salpingo-oophorectomy were significantly older at the time of genetic testing than those with timely risk-reducing bilateral salpingo-oophorectomy (mean, 49.8 vs 36.3 years; P<.001). Of the 306 patients who underwent risk-reducing bilateral salpingo-oophorectomy, those with delayed risk-reducing bilateral salpingo-oophorectomy had a significantly shorter interval between BRCA identification and risk-reducing bilateral salpingo-oophorectomy than those with timely risk-reducing bilateral salpingo-oophorectomy (median, 8.7 vs 17.6 months; P<.001). Patients with delay in risk-reducing bilateral salpingo-oophorectomy were more likely to have a personal history of cancer than those with timely risk-reducing bilateral salpingo-oophorectomy (49.8% vs 37.5%; P=.028). Of the 239 women with delay in risk-reducing bilateral salpingo-oophorectomy, 188 (78.7%) had delayed BRCA mutation identification, 29 (12.1%) had menopausal concerns, 17 (7.1%) had ongoing cancer treatment, 12 (5.0%) had coordination with breast surgery, 20 (8.4%) had miscellaneous reasons, and 19 (7.9%) had no reason documented. In the multivariate model, older age at BRCA diagnosis (odds ratio, 0.73; 95% confidence interval, 0.68-0.78; P<.001) was significantly associated with delayed risk-reducing bilateral salpingo-oophorectomy timing; those with BRCA2 mutation type were 7.54 times as likely to have timely risk-reducing bilateral salpingo-oophorectomy than BRCA1 mutation carriers (odds ratio, 7.54; 95% confidence, 3.70-16.42; P<.001). Nearly 38% of BRCA1 and BRCA2 mutation carriers undergo or have yet to undergo risk-reducing bilateral salpingo-oophorectomy over the recommended National Comprehensive Cancer Network age. The most common reason for the delay in risk-reducing bilateral salpingo-oophorectomy was delayed identification of BRCA mutation, noted in 79% of patients with delayed risk-reducing bilateral salpingo-oophorectomy. Timely genetic testing for eligible patients can increase appropriately timed risk-reducing bilateral salpingo-oophorectomy for the prevention of ovarian cancer and reduction of mortality in BRCA mutation carriers.

Patient cost sharing during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment in ovarian cancer

More patients with ovarian cancer are being treated with poly(adenosine diphosphate-ribose) polymerase inhibitors because regulatory agencies have granted these drugs new approvals for a variety of treatment indications. However, poly(adenosine diphosphate-ribose) polymerase inhibitors are expensive. When administered as a maintenance therapy, these drugs may be administered for months or years. How much of this cost patients experience as out-of-pocket spending is unknown. This study aimed to estimate the out-of-pocket spending that patients experience during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment and to characterize which healthcare services account for that spending. A retrospective cohort study was performed with a sample of patients with ovarian cancer treated between 2014 and 2017 with olaparib, niraparib, or rucaparib. Patients were identified using MarketScan, a health insurance claims database. All insurance claims during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment were collected. The primary outcome variable was the patients' out-of-pocket spending (copayment, coinsurance, and deductibles) during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment for the medication itself. Other outcomes of interest included out-of-pocket spending for other healthcare services, the types and frequency of other healthcare services used, health plan spending, the estimated proportion of patients' household income used each month for healthcare, and patients' out-of-pocket spending immediately before poly(adenosine diphosphate-ribose) polymerase inhibitor treatment. We identified 503 patients with ovarian cancer with a median age of 55 years (interquartile range, 50-62 years); 83% of those had out-of-pocket spendings during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment. The median treatment duration was 124 days (interquartile range, 66-240 days). The mean out-of-pocket spending for poly(adenosine diphosphate-ribose) polymerase inhibitors was $305 (standard deviation, $2275) per month. On average, this accounted for 44.8% (standard deviation, 34.8%) of the patients' overall monthly out-of-pocket spending. The mean out-of-pocket spending for other healthcare services was $165 (standard deviation, $769) per month. Health plans spent, on average, $12,661 (standard deviation, $15,668) per month for poly(adenosine diphosphate-ribose) polymerase inhibitors and $7108 (standard deviation, $15,254) per month for all other healthcare services. The cost sharing for office visits, laboratory tests, and imaging studies represented the majority of non-poly(adenosine diphosphate-ribose) polymerase inhibitor treatment out-of-pocket spending. The average amount patients paid for all healthcare services per month during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment was $470 (standard deviation, $2407), which was estimated to be 8.7% of the patients' monthly household income. The mean out-of-pocket spending in the 12 months before poly(adenosine diphosphate-ribose) polymerase inhibitor treatment was $3110 (standard deviation, $6987). Patients can face high out-of-pocket costs for poly(adenosine diphosphate-ribose) polymerase inhibitors, although the sum of cost sharing for other healthcare services used during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment is often higher. The spending on healthcare costs consumes a large proportion of these patients' household income. Patients with ovarian cancer experience high out-of-pocket costs for healthcare, both before and during poly(adenosine diphosphate-ribose) polymerase inhibitor treatment.

Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study

Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with 10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; P For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.

Vaginal dermoid cyst

Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone

Pelvic lymph node metastasis carries the highest impact on decreased survival among surgical-pathological risk factors for early-stage cervical cancer. Although concurrent administration of chemotherapy during postoperative radiotherapy is the current standard treatment for surgically treated high-risk early-stage cervical cancer, its effectiveness specific to node-positive disease has not been completely studied. To examine the association between the use of concurrent chemotherapy and survival in women with early-stage cervical cancer and nodal metastasis receiving adjuvant radiotherapy. This is a population-based cohort study using the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Women with stage T1-2 cervical cancer with pelvic lymph node metastasis who underwent hysterectomy and received postoperative radiotherapy were examined. Trends, characteristics, and overall survival were compared between women who received postoperative radiotherapy alone (n = 729) or in combination with concurrent chemo-radiotherapy (n = 1809). Propensity score-based inverse probability of treatment weighting was used to account for the effect of measured covariates on treatment selection. Among 2538 women, there was a marked increase in the use of concurrent chemotherapy from 1997 to 2000 (20.7% to 78.5%, P = .052), followed by a more gradual rise through 2016 (88.3%, P .05). Despite the marked increase in the use of concurrent chemo-radiotherapy for women with early-stage cervical cancer and nodal metastases, there was no association between use of concurrent chemotherapy during postoperative radiotherapy and improved survival.

Disparities in biomarker testing in ovarian cancer: a real-world analysis

Prevalence of abnormal cervical cancer screening outcomes among women in the United States: results from the National Health Interview Survey, 2018

Diagnostic performance of ultrasound in assessing the extension of disease in advanced ovarian cancer

Surgical exploration remains the gold standard for evaluating the extension of disease and predicting resectability. A laparoscopy-based scoring model was developed by Fagotti and colleagues in 2006 and updated in 2015, based on the intraoperative presence or absence of some specific cancer features. The model proved an overall accuracy rate of 77% to 100% and is considered the reference test for assessing resectability in our institution. The primary aim of the study was to analyze the agreement between preoperative ultrasound examination and laparoscopic findings in assessing the extension of intraabdominal disease using 6 parameters described by Fagotti's score. This was a prospective single-center observational study. Between January 2019 and June 2020, consecutive patients with clinical or radiological suspicion of ovarian or peritoneal cancer were assessed with preoperative ultrasound examination and assigned a score based on the 6 Fagotti score parameters (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel disease). Presence of mesenteral retraction of the small bowel and miliary carcinomatosis on the serosa were also evaluated. Each parameter was correlated with laparoscopic findings. Concordance was calculated between ultrasound and laparoscopic parameters using Cohen's kappa. Cohen's kappa ranged from 0.70 to 0.90 for carcinomatosis on the small or large bowel, supracolic omentum, liver surface, and diaphragms. Cohen's kappa test was lower for carcinomatosis on the parietal peritoneum (k=0.63) and on the lesser omentum or lesser curvature of the stomach or spleen (k=0.54). The agreement between ultrasound and surgical predictive index value (score) was k=0.74. For the evaluation of mesenteral retraction and miliary carcinomatosis, the agreement was low (k=0.57 and k=0.36, respectively). The results of ultrasound and laparoscopy in the assessment of intraabdominal tumor spread were in substantial agreement for almost all the parameters. Ultrasound examination can play a useful role in the preoperative management of patients with ovarian cancer when used in dedicated referral centers.

Role of 3-dimensional ultrasound in ovarian cancer staging

Survival following minimally invasive radical hysterectomy for patients with cervical carcinoma and tumor size ≤2 cm

Risk of cervical precancer and cancer among uninsured and underserved women from 2009 to 2017

New guidelines for managing cervical precancer among women in the United States use risk directly to guide clinical actions for individuals who are being screened. These risk-based management guidelines have previously only been based on risks from a large integrated healthcare system. We present here data representative of women of low income without continuous insurance coverage to inform the 2019 guidelines and ensure applicability. We examined the risks of high-grade precancer after human papillomavirus and cytology tests in underserved women and assessed the applicability of the 2019 guidelines to this population. We examined cervical cancer screening and follow-up data among 363,546 women enrolled in the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program from 2009 to 2017. We estimated the immediate (prevalent) risks of cervical intraepithelial lesion grade 3 or cancer by using prevalence-incidence mixture models. Risks were estimated for each combination of human papillomavirus and cytology result and were stratified by screening history. We compared these risks with published estimates used in new risk-based management guidelines. Women who were up-to-date with their screening, defined as being screened with cytology within the past 5 years, had immediate risks of cervical intraepithelial neoplasia grade 3 or higher similar to that of women at Kaiser Permanente Northern California, whose data were used to develop the management guidelines. However, women in the Centers for Disease Control and Prevention's National Breast and Cervical Cancer Early Detection Program had greater immediate risks if they were never screened or not up-to-date with their screening. New cervical risk-based management guidelines are applicable for underinsured and uninsured women with a low income in the United States who are up-to-date with their screening. The increased risk observed here among women who received human papillomavirus-positive, high-grade cytology results, who were never screened, or who were not up-to-date with their cervical cancer screening, led to a recommendation in the management guidelines for immediate treatment among these women.

Evaluation of guidelines for observational management of cervical intraepithelial neoplasia 2 in young women

A high rate of regression in young women with cervical intraepithelial neoplasia grade 2 has been recorded. However, there are few prospective data by which to evaluate management guidelines. This study evaluates the American Society for Colposcopy and Cervical Pathology recommendations for follow-up of young women with cervical intraepithelial neoplasia 2 using data created by a large prospective multicenter study of observational management. Participants were 616 women under 25 years with biopsy-diagnosed cervical intraepithelial neoplasia 2 following a referral to colposcopy for an abnormal smear with no previous high-grade abnormality. The protocol included colposcopy, cytology, and colposcopically directed biopsy at the initial visit and at 6- and 12-month follow-ups visits, and these data were analyzed. Histology from the corresponding cervical biopsy was treated as the reference diagnostic test. For young women with cervical intraepithelial neoplasia 2, we aimed to determine the following: (1) the ability of colposcopy to identify women with cervical intraepithelial neoplasia 3 or worse at 6 months; and (2) the ability of colposcopy, cytology, and a combination of cytology and colposcopy to identify residual high-grade abnormalities at 12 months. In addition, although not specified in the guidelines, we investigated the ability of high-risk human papillomavirus positivity alone or with cytology as a co-test to identify residual high-grade abnormalities at 12 months. At 6 months, cervical intraepithelial neoplasia 3+ colposcopic appearance identified only 28% (95% confidence interval, 18-40%) of women diagnosed with cervical intraepithelial neoplasia 3. At 12 months, a high-grade colposcopic appearance identified only 58% (95% confidence interval, 48-68%) of women with residual histological cervical intraepithelial neoplasia 2 or 3. At 12 months, high-grade cytology identified only 58% (95% confidence interval, 48-68%) of women with cervical intraepithelial neoplasia 2 or 3. However, the combination of either high-grade cytology or colposcopic appearance proved substantially more sensitive (81%; 95% confidence interval, 72-88%). High-risk human papillomavirus positivity at 12 months was a sensitive (96%; 95% confidence interval, 89-99%) indicator of persisting high-grade histology. However, this sensitivity came at the expense of specificity (52%; 95% confidence interval, 45-58%). A co-test of high-risk human papillomavirus positivity or high-grade cytology at 12 months provided a high sensitivity (97%; 95% confidence interval, 90-99%) but low specificity (51%; 95% confidence interval, 45%-58%). Colposcopy and cytology are limited in their ability to exclude persistent high-grade abnormality for young women undergoing observational management for cervical intraepithelial neoplasia 2. We recommend biopsy for all women at 12 months. High-risk human papillomavirus positivity is a sensitive indicator of persistent abnormality and should be considered in those not having a biopsy.

Incidence of adverse events in minimally invasive vs open radical hysterectomy in early cervical cancer: results of a randomized controlled trial

Standard treatment of early cervical cancer involves a radical hysterectomy and retroperitoneal lymph node dissection. The existing evidence on the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer is either nonrandomized or retrospective. The purpose of this study was to compare the incidence of adverse events after minimally invasive vs open radical hysterectomy for early cervical cancer. The Laparoscopic Approach to Carcinoma of the Cervix trial was a multinational, randomized noninferiority trial that was conducted between 2008 and 2017, in which surgeons from 33 tertiary gynecologic cancer centers in 24 countries randomly assigned 631 women with International Federation of Gynecology and Obstetrics 2009 stage IA1 with lymph-vascular invasion to IB1 cervical cancer to undergo minimally invasive (n = 319) or open radical hysterectomy (n = 312). The Laparoscopic Approach to Carcinoma of the Cervix trial was suspended for enrolment in September 2017 because of an increased risk of recurrence and death in the minimally invasive surgery group. Here we report on a secondary outcome measure: the incidence of intra- and postoperative adverse events within 6 months after surgery. Of 631 randomly assigned patients, 536 (85%; mean age, 46.0 years) met inclusion criteria for this analysis; 279 (52%) underwent minimally invasive radical hysterectomy, and 257 (48%) underwent open radical hysterectomy. Of those, 300 (56%), 91 (16.9%), and 69 (12.8%) experienced at least 1 grade ≥2 or ≥3 or a serious adverse event, respectively. The incidence of intraoperative grade ≥2 adverse events was 12% (34/279 patients) in the minimally invasive group vs 10% (26/257) in the open group (difference, 2.1%; 95% confidence interval, -3.3 to 7.4%; P=.45). The overall incidence of postoperative grade ≥2 adverse events was 54% (152/279 patients) in the minimally invasive group vs 48% (124/257) in the open group (difference, 6.2%; 95% confidence interval, -2.2 to 14.7%; P=.14). For early cervical cancer, the use of minimally invasive compared with open radical hysterectomy resulted in a similar overall incidence of intraoperative or postoperative adverse events.

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Frequency of high-grade squamous cervical lesions among women over age 65 years living with HIV

Current US cervical cancer screening guidelines recommend screening cessation at the age of 65 years provided women have adequate previous screening and no history of precancer. Women living with HIV are at higher risk of cervical cancer than women living without HIV. Furthermore, limited data exists to quantify the risk of cervical cancer among women who otherwise would qualify for screening cessation. This study aimed to determine whether guidelines recommending women to discontinue cervical cancer screening at the age of 65 years are appropriate for women living with HIV. Semiannual Papanicolaou testing was performed as part of surveillance visits in the Women's Interagency HIV Study. Launched in October 1994, the Women's Interagency HIV Study is a federally funded US multisite cohort study that has enrolled 3678 women living with HIV and 1304 women living without HIV; we included data throughout September 2019 onward. Conventional Papanicolaou tests were collected at scheduled 6-month visits and read centrally according to the 1991 Bethesda System criteria. Results were analyzed among women at least 65 years of age. The primary endpoint was high-grade cytology, including high-grade squamous intraepithelial lesions; atypical glandular cells; atypical squamous cells, cannot exclude high-grade lesions; and malignant cytology. Wilcoxon rank-sum tests were used to compare the continuous variables, and Chi-square tests or the Fisher exact tests were used to compare the categorical variables. The Kaplan-Meier method was used to calculate the cumulative incidence. Poisson regression was used to compare 2 incidence rates. Of 169 eligible women (121 women living with HIV and 48 women living without HIV) who contributed 678.4 person-years of observation after reaching the age of 65 years, 2.2% had high-grade cytologic abnormalities. However, no cancer was found. Furthermore, 20 women had previous precancer results, and 74 women had abnormal Papanicolaou test results in the previous decade. Among 50 women (38 women living with HIV and 12 women living without HIV) with a previous hysterectomy and no history of cervical precancer, the cumulative incidence rates of high-grade squamous intraepithelial lesions were 0.6 (95% confidence interval, 0.0-3.2) per 100 person-years for women living with HIV and 0.0 (95% confidence interval, 0.0-8.1) per 100 person-years for women living without HIV (P=.61). Only 48 women (27 women living with HIV and 21 women living without HIV) had cervices and met the current guidelines to discontinue screening; their risk of experiencing high-grade squamous intraepithelial lesions was 2.2 (95% confidence interval, 0.6-5.5) per 100 person-years overall and did not vary by HIV status (2.3 [95% confidence interval, 0.5-6.8] per 100 person-years for women living with HIV and 1.8 [95% confidence interval, 0.0-9.8] per 100 person-years for women living without HIV; P=.81). Most women living with HIV do not meet the criteria for cervical cancer screening cessation and will need to continue screening over the age of 65 years; however, women who meet the criteria for screening cessation have risks of high-grade squamous lesions similar to women living without HIV and may choose to discontinue.

Trends in the use of indocyanine green for sentinel lymph node mapping in vulvar cancer

Trends in human papillomavirus vaccination among women aged 27 to 45 years, from 2017 to 2019

Ovarian cancer risk among older patients with stable adnexal masses

Few studies have evaluated the risk of cancer among older patients with stable adnexal masses in community-based settings to determine the duration of observation time needed. This study aimed to assess the ovarian cancer risk among older patients with stable adnexal masses on ultrasound. This was a retrospective cohort study of patients in a large community-based health system aged ≥50 years with an adnexal mass 1 cm in the greatest dimension or a change in standardized reported ultrasound characteristics. Ovarian cancer risk was determined at increasing time intervals of stability after initial ultrasound. Among 4061 patients with stable masses, the average age was 61 years (range, 50-99), with an initial mass size of 3.8 cm (range, 0.2-9.9). With a median follow-up of 3.7 years, 11 cancers were detected, with an absolute risk of 0.27%. Ovarian cancer risk declined with longer duration of stability, from 0.73 (95% confidence interval, 0.30-1.17) per 1000 person-years at 6 to 12 weeks, 0.63 (95% confidence interval, 0.19-1.07) at 13 to 24 weeks, 0.44 (95% confidence interval, 0.01-0.87) at 25 to 52 weeks, and 0.00 (95% confidence interval, 0.00-0.00) at >52 weeks. Expressed as number needed to reimage, ongoing ultrasound imaging would be needed for 369 patients whose masses show stability at 6 to 12 weeks, 410 patients at 13 to 24 weeks, 583 patients at 25 to 52 weeks, and >1142 patients with stable masses at 53 to 104 weeks to detect 1 case of ovarian cancer. In a diverse community-based setting, among patients aged ≥50 years with an adnexal mass that was stable for at least 6 weeks after initial ultrasound, the risk of ovarian cancer was very low at 0.27%. Longer demonstrated duration of stability was associated with progressively lower risk, with no cancer cases observed after 52 weeks of stability. These findings suggest that the benefit of ultrasound monitoring of stable masses beyond 12 months is minimal and may be outweighed by potential risks of repeated imaging.

Sentinel lymph node biopsy for vulvar melanoma: trends in tumor stage-specific utilization

Episiotomy-site clear cell carcinoma

Cutaneous T-cell lymphoma of the vulva

Combination therapy with topotecan, paclitaxel, and bevacizumab improves progression-free survival in patients with recurrent high-grade neuroendocrine cervical cancer: a Neuroendocrine Cervical Tumor Registry (NeCTuR) study

Recurrent high-grade neuroendocrine cervical cancer has a very poor prognosis and limited active treatment options. This study aimed to evaluate the efficacy of the 3-drug regimen of topotecan, paclitaxel, and bevacizumab in women with recurrent high-grade neuroendocrine cervical cancer. This retrospective cohort study used data from the Neuroendocrine Cervical Tumor Registry (NeCTuR), which include data abstracted directly from medical records of women diagnosed with high-grade neuroendocrine carcinoma of the cervix from English- and Spanish-speaking countries. The study compared women with recurrent high-grade neuroendocrine cervical cancer who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and women with recurrent high-grade neuroendocrine cervical cancer who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen. Patients continued chemotherapy until disease progression or the development of unacceptable toxic effects. Progression-free survival from the start of therapy for recurrence to the next recurrence or death, overall survival from the first recurrence, and response rates were evaluated. The study included 62 patients who received the topotecan, paclitaxel, and bevacizumab regimen as first- or second-line therapy for recurrence and 56 patients who received chemotherapy but not the topotecan, paclitaxel, and bevacizumab regimen for recurrence. The median progression-free survival rates were 8.7 months in the topotecan, paclitaxel, and bevacizumab regimen group and 3.7 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for disease progression of 0.27 (95% confidence interval, 0.17-0.48; P<.0001). In the topotecan, paclitaxel, and bevacizumab regimen group, 15% of patients had stable disease, 39% of patients had a partial response, and 18% of patients had a complete response. Compared with patients in the non-topotecan, paclitaxel, and bevacizumab regimen group, significantly more patients in the topotecan, paclitaxel, and bevacizumab regimen group remained on treatment at 6 months (31% vs 67%, respectively; P=.0004) and 1 year (9% vs 24%, respectively; P=.02). The median overall survival rates were 16.8 months in the topotecan, paclitaxel, and bevacizumab regimen group and 14.0 months in the non-topotecan, paclitaxel, and bevacizumab regimen group, with a hazard ratio for death of 0.87 (95% confidence interval, 0.55-1.37). Combination therapy with topotecan, paclitaxel, and bevacizumab was an active regimen in women with recurrent high-grade neuroendocrine cervical cancer and improved progression-free survival while decreasing the hazard ratio for disease progression.

Relationship between unremoved cervical polyp in pregnancy and spontaneous preterm birth

Cervical polyps removed during pregnancy have been reported to be associated with preterm birth; however, the association between unremoved cervical polyps and preterm birth has not been elucidated. This study aimed to clarify the relationship between cervical polyps detected before 12 weeks of gestation managed expectantly and spontaneous preterm birth. This retrospective cohort study included pregnant women who visited a tertiary perinatal center before 12 weeks of gestation between January 2015 and December 2019. The exclusion criteria were as follows: multiple gestations, loss or termination of pregnancy before 12 weeks of gestation, major fetal anomalies, fetal chromosomal abnormalities, fetal demise, having undergone removal of cervical polyps before the first visit to our hospital, and moving to other hospitals before delivery. A vaginal speculum examination was routinely performed during a prenatal visit before 12 weeks of gestation. When a cervical polyp was detected on speculum examination, it was managed expectantly, unless gynecologic malignancy was suspected. Relationships between cervical polyps and spontaneous preterm birth before 34 weeks of gestation were evaluated using logistic regression analysis and Cox proportional-hazards analysis adjusted for known confounders for spontaneous preterm birth. A total of 4172 pregnant women were included, of whom 92 (2.2%) had a cervical polyp detected before 12 weeks of gestation. None of the women underwent polypectomy during pregnancy. The incidence of spontaneous preterm birth before 34 weeks of gestation was higher in pregnant women with cervical polyps than in those without them (5.4% vs 0.7%; P<.01). Logistic regression analysis revealed that cervical polyps were an independent risk factor for spontaneous preterm birth before 34 weeks of gestation (adjusted odds ratio, 4.09; 95% confidence interval, 1.70-9.81; P<.01). The adjusted hazard ratio for spontaneous preterm birth before 34 weeks of gestation among women with vs without cervical polyps was 2.95 (95% confidence interval, 1.32-6.62; P<.01). Cervical polyps detected before 12 weeks of gestation managed expectantly are a significant risk factor for spontaneous preterm birth before 34 weeks of gestation.

Salpingectomy in individuals at high risk for tubo-ovarian cancer: consensus and precaution

Tubo-ovarian carcinoma, particularly high-grade serous carcinoma, is one of the most lethal gynecologic malignancies, largely due to its late-stage diagnosis and lack of effective screening strategies. For individuals with hereditary pathogenic variants in genes associated with ovarian cancer such as BRCA1, BRCA2, RAD51C, RAD51D, BRIP1, PALB2, and Lynch syndrome-associated genes, the National Comprehensive Cancer Network recommends risk-reducing salpingo-oophorectomy, which has been shown to decrease mortality. However, premenopausal oophorectomy can result in substantial quality-of-life impairments, and as a result, many high-risk individuals delay or forego risk-reducing salpingo-oophorectomy despite its proven mortality benefit. The discovery that most high-grade serous carcinomas originate in the fallopian tubes has led to interest in a novel preventive strategy: risk-reducing salpingectomy followed by delayed oophorectomy in high-risk individuals. In this clinical opinion, we describe that while risk-reducing salpingectomy with delayed oophorectomy has been associated with improved menopause-related quality of life and reduced cancer worry, its efficacy in cancer risk reduction has not been established. We explain the importance of offering risk-reducing salpingectomy with delayed oophorectomy within clinical trials whenever possible.

Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention

Improved technologies paired with an increase in access to genetic testing have led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time when precancer screening, chemoprevention, and/or risk-reducing surgery may be beneficial. This study aimed to inform clinical decision-making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. A decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years were used to simulate the lifespan of patients. The setting was obstetrical clinics in the United States, and the participants were a theoretical cohort of 1,429,074 pregnant patients who annually underwent expanded carrier screening. Among our cohort, BRCA1 testing resulted in the identification of an additional 3716 BRCA1-positive patients, the prevention of 1394 breast and ovarian cancer cases, and 1084 fewer deaths. BRCA1 testing was a cost-effective strategy compared with no BRCA1 testing with an incremental cost-effectiveness ratio of $86,001 per quality-adjusted life years. In a 1-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0.00% to 20.00% and found that BRCA1 testing continued to be the cost-effective strategy until the prevalence rate was reduced to 0.16%. Multiple additional sensitivity analyses did not substantially affect the cost-effectiveness. The addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Single-cell technology: the key to an improved understanding of the human endometrium in health and disease

Cyclic exposure of the endometrium to ovarian sex steroids during the menstrual cycle induces a transition between proliferative and receptive states involving a different variety of cell types (ie, epithelial, stromal, endothelial, and immune cells) in preparation for embryo implantation during the narrow window of implantation. The study of the female reproductive system cells across these different phases contributes to our understanding of the healthy endometrium at the cellular level, supporting comparisons with pathological conditions, such as endometriosis, endometrial cancer, or Asherman's syndrome. Single-cell RNA sequencing technology represents a powerful tool that can discern the gene expression profiles of each cell within a tissue sample and has recently revealed the complex collaborations taking place between diverse cell types during the distinct endometrial phases. This review aims to summarize those studies that have employed single-cell RNA sequencing to deepen our understanding of the endometrium at single-cell resolution during the menstrual cycle. We discuss the transitions taken by distinct cell populations across the proliferative and secretory phases and the general importance of these transitions to successful embryo implantation. Furthermore, we analyze the use of single-cell RNA sequencing technology to study in vitro models of healthy endometrium and endometrial carcinoma. We believe that future studies using single-cell RNA sequencing will be essential to understanding the behavior of the endometrium as a whole and identifying potential avenues for the improved management of endometrial diseases.

Survival outcomes comparing minimally invasive versus open cytoreductive surgery in recurrent adult-type granulosa cell tumors

Adult-type granulosa cell tumors are a rare form of ovarian cancer, 30% of which will recur. Cytoreductive surgery is often performed at the time of a first recurrence, but little is known about the impact of open versus minimally invasive surgical approaches on survival outcomes. To examine associations between surgical approach, clinical variables, and survival outcomes among patients with adult-type granulosa cell tumors who underwent cytoreductive surgery at the time of first recurrence. This is a retrospective cohort study of patients with adult-type granulosa cell tumors enrolled in the MD Anderson Rare Gynecologic Malignancy Registry as of April 2024. Included patients had at least one documented recurrence and underwent secondary cytoreductive surgery as part of their treatment plan. Patients were excluded if surgery was performed prior to January 1, 2000, or if surgery was not intraabdominal. Demographics and clinical variables were compared using descriptive statistics. Surgical complexity was classified as either low, intermediate, or high based on procedures performed. Progression-free and overall survival outcomes were stratified by surgical approach and estimated using Kaplan-Meier curves. A multivariable Cox proportional hazards model was used to adjust progression-free survival at time of first recurrence for age, year of surgery, and extent of disease. Four hundred eighty-five patients with adult granulosa cell tumors were identified, 108 met inclusion criteria. Seventy-eight (72%) had open and 30 (28%) had minimally invasive secondary cytoreductive surgery. Baseline characteristics, including initial stage, self-identified race, or age at diagnosis, did not differ between open and minimally invasive surgery groups. Patients undergoing minimally invasive surgery were significantly younger at the time of surgery than the open group, with a median age of 42 vs 49, respectively (P=.03). For the open group, 33% of surgeries were considered intermediate complexity and 4% high complexity, compared to 7% and 0% in the minimally invasive surgery group, respectively (P=.004). There was no difference in achieving optimal cytoreduction, 85% in the open group and 88% in the minimally invasive surgery group (P=.68). Following secondary cytoreductive surgery, there was no difference in overall survival, median overall survival of 166 months in the open group and 94 months in the minimally invasive group (P=.27), or progression-free survival after first recurrence, 26 months in the open group compared to 21 months in the minimally invasive group (P=.42). The difference in progression-free survival after the first recurrence remained nonsignificant after adjustment for key potential variables, including age, surgical approach, year of surgery, and extent of disease. There was no difference in incisional or port site recurrences at the time of second recurrence among those undergoing open (8.3%) compared to minimally invasive surgery (7.4%) at time of first recurrence (P=.89). In patients with a first recurrence of adult-type granulosa cell tumors, open secondary cytoreductive surgery did not achieve superior outcomes compared to surgery via a minimally invasive approach. Minimally invasive surgery should be considered for carefully selected patients with recurrent adult-type granulosa cell tumors. Future research is needed on patient factors important to the selection of surgical approach in this setting.

Cancer diagnosis during pregnancy is associated with severe maternal and neonatal morbidity

Data on maternal and fetal outcomes in patients diagnosed with cancer during pregnancy are limited. Given expected increase in patients diagnosed with cancer during pregnancy, there is a growing need to evaluate clinical outcomes. To evaluate obstetric outcomes among women with early-stage gynecologic or breast cancer who were diagnosed during pregnancy compared to women without cancer in a population-based cohort. We performed a population-based study of women aged 18 to 45 years with stage I gynecologic or stage I to III breast cancer reported to the California Cancer Registry for the years 2000 to 2012. Data were linked to the 2000 to 2012 California birth data to produce a database with cancer characteristics and obstetric outcomes. We included patients who had a delivery within the 10 months following cancer diagnosis. The primary outcome was severe maternal morbidity. Secondary outcomes included preterm birth and neonatal morbidity. Propensity scores were used to match similar controls to cases in a 2:1 ratio based on demographic attributes and medical comorbidities included in the Obstetric Comorbidity Index. Logistic regressions were used to evaluate outcomes. The cohort consisted of 503 women with cancer in pregnancy (319 breast, 125 ovarian, 59 cervical) and 1006 matched controls. Cancer during pregnancy was associated with higher odds of severe maternal morbidity (6.8% vs <1.1%; odds ratio 8.03, 95% confidence interval 3.82-16.88), preterm birth between 32 and 36 weeks (32.6% vs 8.3%, odds ratio 5.38, 95% confidence interval 4.02-7.20), and neonatal morbidity (12.5% vs 6.1%; odds ratio 2.22, 95% confidence interval 1.53-3.21) compared to matched controls. In subanalysis of severe maternal morbidity indicators, hysterectomy and sepsis were significantly associated with cancer during pregnancy (4.8% vs <1.1%, P<.001; <2.2% vs 0.0%, P=.037, respectively). Cancer during pregnancy is associated with increased risk of maternal and neonatal morbidity. These findings highlight the need for careful management and consideration of obstetric outcomes in these patients.

Fertility-preserving treatment for stage IA endometrial cancer: a systematic review and meta-analysis

The increasing use of fertility-preserving treatments in reproductive-aged patients with early-stage endometrial cancer necessitates robust evidence on the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device. We conducted a systematic review and meta-analysis to examine the outcomes following these 2 primary progestin-based therapies in reproductive-aged patients with early-stage endometrial cancer. We conducted a systematic review of observational studies and randomized controlled trials following the Cochrane Handbook guidance. We conducted a literature search of 5 databases and 1 trial registry from inception of the study to April 16, 2024. Studies reporting complete response within 1 year in reproductive-aged patients with clinical stage IA endometrioid cancer undergoing progestin therapy treatment were included. We used data from both observational and randomized controlled studies. The primary exposure assessed was the type of progestational treatment (oral progestins or LNG-IUD). The primary outcome was the pooled proportion of the best complete response (CR) within 1 year of primary progestational treatment. We performed a proportional meta-analysis to estimate the treatment response. Sensitivity analyses were performed by removing studies with extreme effect sizes or removing grade 2 tumors. The risk of bias was assessed in each study using the Joanna Briggs Institute critical appraisal checklist. Our analysis involved 754 reproductive-aged patients diagnosed with endometrial cancer, with 490 receiving oral progestin and 264 receiving levonorgestrel-releasing intrauterine device as their primary progestational treatment. The pooled proportion of the best complete response within 12 months of oral progestin and levonorgestrel-releasing intrauterine device treatment were 66% (95% CI, 55-76) and 86% (95% CI, 69-95), respectively. After removing outlier studies, the pooled proportion was 66% (95% CI, 57-73) for the oral progestin group and 89% (95% CI, 75-96) for the levonorgestrel-releasing intrauterine device group, showing reduced heterogeneity. Specifically, among studies including grade 1 tumors, the pooled proportions were 66% (95% CI, 54-77) for the oral progestin group and 83% (95% CI, 50-96) for the levonorgestrel-releasing intrauterine device group. The pooled pregnancy rate was 58% (95% CI, 37-76) after oral progestin treatment and 44% (95% CI, 6-90) after levonorgestrel-releasing intrauterine device treatment. This meta-analysis provides valuable insights into the effectiveness of oral progestins and levonorgestrel-releasing intrauterine device treatment within a 12-month timeframe for patients with early-stage endometrial cancer who desire to preserve fertility. These findings have the potential to assist in personalized treatment decision-making for patients.

Racial and ethnic differences in early death among gynecologic malignancy

Racial and ethnic differences in early death after cancer diagnosis have not been well studied in gynecologic malignancy. This study aimed to assess population-level trends and characteristics of early death among patients with gynecologic malignancy based on race and ethnicity in the United States. The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was queried to examine 461,300 patients with gynecologic malignancies from 2000 to 2020, including uterine (n=242,709), tubo-ovarian (n=119,989), cervical (n=68,768), vulvar (n=22,991), and vaginal (n=6843) cancers. Early death, defined as a mortality event within 2 months of the index cancer diagnosis, was evaluated per race and ethnicity. At the cohort level, early death occurred in 21,569 patients (4.7%), including 10.5%, 5.5%, 2.9%, 2.5%, and 2.4% for tubo-ovarian, vaginal, cervical, uterine, and vulvar cancers, respectively (P<.001). In a race- and ethnicity-specific analysis, non-Hispanic Black patients with tubo-ovarian cancer had the highest early death rate (14.5%). Early death racial and ethnic differences were the largest in tubo-ovarian cancer (6.4% for Asian vs 14.5% for non-Hispanic Black), followed by uterine (1.6% for Asian vs 4.9% for non-Hispanic Black) and cervical (1.8% for Hispanic vs 3.8% to non-Hispanic Black) cancers (all, P<.001). In tubo-ovarian cancer, the early death rate decreased over time by 33% in non-Hispanic Black patients from 17.4% to 11.8% (adjusted odds ratio, 0.67; 95% confidence interval, 0.53-0.85) and 23% in non-Hispanic White patients from 12.3% to 9.5% (adjusted odds ratio, 0.77; 95% confidence interval, 0.71-0.85), respectively. The early death between-group difference diminished only modestly (12.3% vs 17.4% for 2000-2002 [adjusted odds ratio for non-Hispanic White vs non-Hispanic Black, 0.54; 95% confidence interval, 0.45-0.65] and 9.5% vs 11.8% for 2018-2020 [adjusted odds ratio, 0.65; 95% confidence interval, 0.54-0.78]). Overall, approximately 5% of patients with gynecologic malignancy died within the first 2 months from cancer diagnosis, and the early death rate exceeded 10% in non-Hispanic Black individuals with tubo-ovarian cancer. Although improving early death rates is encouraging, the difference among racial and ethnic groups remains significant, calling for further evaluation.

A modified diffusion-weighted magnetic resonance imaging–based model from the radiologist’s perspective: improved performance in determining the surgical resectability of advanced high-grade serous ovarian cancer

Complete resection of all visible lesions during primary debulking surgery is associated with the most favorable prognosis in patients with advanced high-grade serous ovarian cancer. An accurate preoperative assessment of resectability is pivotal for tailored management. This study aimed to assess the potential value of a modified model that integrates the original 8 radiologic criteria of the Memorial Sloan Kettering Cancer Center model with imaging features of the subcapsular or diaphragm and mesenteric lesions depicted on diffusion-weighted magnetic resonance imaging and growth patterns of all lesions for predicting the resectability of advanced high-grade serous ovarian cancer. This study included 184 patients with high-grade serous ovarian cancer who underwent preoperative diffusion-weighted magnetic resonance imaging between December 2018 and May 2023 at 2 medical centers. The patient cohort was divided into 3 subsets, namely a study cohort (n=100), an internal validation cohort (n=46), and an external validation cohort (n=38). Preoperative radiologic evaluations were independently conducted by 2 radiologists using both the Memorial Sloan Kettering Cancer Center model and the modified diffusion-weighted magnetic resonance imaging-based model. The morphologic characteristics of the ovarian tumors depicted on magnetic resonance imaging were assessed as either mass-like or infiltrative, and transcriptomic analysis of the primary tumor samples was performed. Univariate and multivariate statistical analyses were performed. In the study cohort, both the scores derived using the Memorial Sloan Kettering Cancer Center (intraclass correlation coefficients of 0.980 and 0.959, respectively; both P<.001) and modified diffusion-weighted magnetic resonance imaging-based models (intraclass correlation coefficients of 0.962 and 0.940, respectively; both P<.001) demonstrated excellent intra- and interobserver agreement. The Memorial Sloan Kettering Cancer Center model (odds ratio, 1.825; 95% confidence interval, 1.390-2.395; P<.001) and the modified diffusion-weighted magnetic resonance imaging-based model (odds ratio, 1.776; 95% confidence interval, 1.410-2.238; P<.001) independently predicted surgical resectability. The modified diffusion-weighted magnetic resonance imaging-based model demonstrated improved predictive performance with an area under the curve of 0.867 in the study cohort and 0.806 and 0.913 in the internal and external validation cohorts, respectively. Using the modified diffusion-weighted magnetic resonance imaging-based model, patients with scores of 0 to 2, 3 to 4, 5 to 6, 7 to 10, and ≥11 achieved complete tumor debulking rates of 90.3%, 66.7%, 53.3%, 11.8%, and 0%, respectively. Most patients with incomplete tumor debulking had infiltrative tumors, and both the Memorial Sloan Kettering Cancer Center and the modified diffusion-weighted magnetic resonance imaging-based models yielded higher scores. The molecular differences between the 2 morphologic subtypes were identified. When compared with the Memorial Sloan Kettering Cancer Center model, the modified diffusion-weighted magnetic resonance imaging-based model demonstrated enhanced accuracy in the preoperative prediction of resectability for advanced high-grade serous ovarian cancer. Patients with scores of 0 to 6 were eligible for primary debulking surgery.

Serial cytoreductive surgery and survival outcomes in recurrent adult-type ovarian granulosa cell tumors

Few studies have evaluated the role of cytoreductive surgery in patients with recurrent adult granulosa cell tumors of the ovary. Despite a multitude of treatment modalities in the recurrent setting, the optimal management strategy is not known. Cytoreductive surgery offers an attractive option for disease confined to the abdomen/pelvis. However, few studies have evaluated the role of surgery compared with systemic therapy alone following the first recurrence and subsequent disease progressions. This study aimed to determine the impact of secondary, tertiary, and quaternary cytoreductive surgery on survival outcomes in recurrent adult granulosa cell tumors of the ovary. This is a multicenter, retrospective cohort study evaluating patients with recurrent adult granulosa cell tumors of the ovary enrolled in the MD Anderson Rare Gynecologic Malignancy Registry from 1970 to 2022. Study inclusion criteria consisted of histology-proven recurrent disease, at least 1 documented recurrence, and treatment/treatment planning at the MD Anderson Cancer Center or Lyndon B. Johnson General Hospital. The primary exposure was cytoreductive surgery, and the outcomes of interest were progression-free survival and overall survival. Survival analyses were restricted to eligible patients with resectable disease without medical barriers to surgery at each progression episode. Demographic and clinicopathologic characteristics were summarized using descriptive statistics. Progression-free survival (after first, second, and third progression) and overall survival were estimated with methods of Kaplan and Meier, and were modeled via Cox proportional hazards regression. Multivariable analyses were performed for progression-free survival after first progression and overall survival. Among the 369 patients with adult granulosa cell tumors of the ovary in the registry, 149 patients met the study inclusion criteria. Secondary cytoreductive surgery was associated with a significant improvement in progression-free survival on univariable (hazard ratio, 0.37; 95% confidence interval, 0.17-0.81, P=.01) and multivariable analyses (hazard ratio, 0.42; 95% confidence interval, 0.19-0.92; P=.03). Those who underwent secondary cytoreductive surgery had a significantly improved median overall survival compared with those who did not undergo cytoreductive surgery (181.92 vs 61.56 months, respectively; P=.002). Overall survival benefit remained statistically significant on multivariable analysis (hazard ratio, 0.28; 95% confidence interval, 0.11-0.67; P=.004). Tertiary cytoreductive surgery was similarly associated with a significant improvement in progression-free survival (hazard ratio, 0.43; 95% confidence interval, 0.26-0.70; P=.001). Despite a similar trend, quaternary cytoreductive surgery was not associated with a significant improvement in progression-free survival (hazard ratio, 0.74; 95% confidence interval, 0.42-1.26; P=.27). Among those with resectable disease and no medical contraindications to surgery, cytoreductive surgery may have a beneficial impact on progression-free survival and overall survival in patients with recurrent adult granulosa cell tumors of the ovary.

Uterine cancer incidence trends and 5-year relative survival by race/ethnicity and histology among women under 50 years

Uterine cancers diagnosed before age 50 years are increasing in the U.S., but changes in clinical characteristics and survival over time across racial/ethnic groups have not been previously described. To investigate age-adjusted, hysterectomy corrected incidence rates and trends, and 5-year relative survival rates of uterine cancer in women aged <50 years, overall and stratified by race/ethnicity and histology. We included microscopically confirmed uterine cancer cases (diagnosed 2000-2019) in women aged 20 to 49 years from the Surveillance, Epidemiology, and End Results Program. Age-adjusted incidence and 5-year relative survival rates, and 95% confidence intervals were computed using Surveillance, Epidemiology, and End Results (SEER) ∗Stat and compared across time periods (2000-2009 and 2010-2019). Incidence rates were adjusted for hysterectomy prevalence using Behavioral Risk Factor Surveillance System data, and trends were computed using the Joinpoint regression program. We included 57,128 uterine cancer cases. The incidence of uterine cancer increased from 10.1 per 100,000 in 2000-2009 to 12.0 per 100,000 in 2010-2019, increasing at an annual rate of 1.7%/y for the entire period. Rising trends were more pronounced among women <40 years (3.0%/y and 3.3%/y in 20-29 and 30-39 years, respectively) than in those 40 to 49 years (1.3%/y), and among underrepresented racial/ethnic groups (Hispanic 2.8%/y, non-Hispanic-Black 2.7%, non-Hispanic-Asian/Pacific Islander 2.1%) than in non-Hispanic-White (0.9%/y). Recent (2010-2019) incidence rates were highest for endometrioid (9.6 per 100,000), followed by sarcomas (1.2), and nonendometrioid subtypes (0.9). Rates increased significantly for endometrioid subtypes at 1.9%/y from 2000 to 2019. Recent endometrioid and nonendometrioid rates were highest in non-Hispanic-Native American/Alaska Native (15.2 and 1.4 per 100,000), followed by Hispanic (10.9 and 1.0), non-Hispanic-Asian/Pacific Islander (10.2 and 0.9), non-Hispanic-White (9.4 and 0.8), and lowest in non-Hispanic-Black women (6.4 and 0.8). Sarcoma rates were highest in non-Hispanic-Black women (1.8 per 100,000). The 5-year relative survival remained unchanged over time for women with endometrioid (from 93.4% in 2000-2009 to 93.9% in 2010-2019, P≥.05) and nonendometrioid subtypes (from 73.2% to 73.2%, P≥.05) but decreased for women with sarcoma from 69.8% (2000-2009) to 66.4% (2010-2019, P<.05). Uterine cancer incidence rates in women <50 years have increased from 2000 to 2019 while survival has remained relatively unchanged. Incidence trends can be primarily attributed to increasing rates of cancers with endometrioid histology, with the greatest increases observed among non-Hispanic-Black, Hispanic, and non-Hispanic-Asian/Pacific Islander. Sarcomas, while much rarer, were the second most common type of uterine cancer among women <50 years and have poor prognosis and apparent decreasing survival over time. Rising rates of uterine cancer and the distinct epidemiologic patterns among women <50 years highlight the need for effective prevention and early detection strategies for uterine cancer in this age group.

Assessment of probiotic and prebiotic use in gynecologic cancer patients: a systematic review

To evaluate evidence on the impact of probiotics and prebiotics on clinical outcomes, treatment efficacy, quality of life, safety, and translational endpoints in patients with gynecologic cancers. A systematic search of PubMed, Embase, and Scopus was conducted in March 2023 and updated through September 2025. Gray literature sources (ClinicalTrials.gov, reference lists) were also reviewed. Eligible studies included randomized controlled trials and prospective interventional studies in women with gynecologic cancers (cervical, endometrial, ovarian, uterine, and vulvar) undergoing treatment. Interventions were probiotic, prebiotic, or dietary fiber supplementation. Eligible outcomes included treatment toxicity, stool consistency, quality of life, postoperative outcomes, oncologic outcomes, safety, and microbiome endpoints. Exclusions were retrospective studies, case reports, reviews, conference abstracts, and studies without cancer-related outcomes. Three independent reviewers screened studies using Covidence, with disagreements resolved by consensus or adjudication. Risk of bias was assessed with the Cochrane Risk of Bias 2.0 tool. Due to heterogeneity in strains, dosing, and outcomes, structured narrative synthesis was conducted rather than meta-analysis. From 2308 screened records, 9 randomized controlled trials involving 663 patients were included. Seven studies evaluated probiotics and 2 assessed prebiotics/fiber. Most focused on radiation-induced toxicity in cervical (n=415) and endometrial cancer (n=170) patients. Probiotics significantly reduced incidence and severity of radiation-induced diarrhea, improved stool consistency, and decreased antidiarrheal use (P<.05). Prebiotics alone showed minimal benefit. One perioperative study found probiotics accelerated bowel recovery and reduced postoperative complications. Three translational studies showed probiotics reduced gut permeability but did not alter microbial composition. No trials examined chemotherapy or immunotherapy outcomes, progression-free survival, or overall survival. Adverse events were infrequent and no major safety concerns were identified. Probiotic supplementation demonstrates consistent benefit in reducing radiation-induced gastrointestinal toxicity in gynecologic cancer patients, while prebiotics alone show limited efficacy. Evidence gaps include effects on chemotherapy, immunotherapy, oncologic outcomes, and survival. Heterogeneity in formulations limits clinical applicability, and standardized strain-specific trials are needed. Future research should evaluate long-term oncologic outcomes, optimize microbiome-directed interventions, and establish safety in immunocompromised populations.

Prognostic role of immunohistochemical and molecular markers in no specific molecular profile endometrial cancer: a systematic review and meta-analysis

No specific molecular profile endometrial cancer represents nearly half of the diagnoses, characterized by substantial molecular heterogeneity and intermediate recurrence and survival outcomes. Currently, no immunohistochemical or molecular markers are established in guidelines to improve prognosis estimation and personalize treatment in no specific molecular profile endometrial cancer. This systematic review and meta-analysis aimed to evaluate the prognostic significance of potential immunohistochemical and molecular surrogate markers in no specific molecular profile endometrial cancers. This systematic review and meta-analysis adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered with the International Prospective Register of Systematic Reviews (CRD42024601035). A comprehensive literature search was conducted using Scopus, PubMed/MEDLINE, ScienceDirect, and the Cochrane Library (January 1994-December 2024). Studies assessing the prognostic roles of L1 cell adhesion molecule, catenin beta 1, AT-rich interactive domain-containing protein 1A, estrogen receptor, progesterone receptor, and STMN1 expression or mutation status in no specific molecular profile endometrial cancers were included. Methodological quality was assessed using the Newcastle-Ottawa Scale and the Quality in Prognosis Studies tool for risk of bias in prognostic studies. Certainty of evidence for each outcome was evaluated using the Grading of Recommendations, Assessment, Development and Evaluation approach. Hazard ratios for recurrence and survival were calculated using random-effects or fixed-effects models depending on heterogeneity. Fourteen retrospective studies including 4654 no specific molecular profile endometrial cancers were analyzed. L1 cell adhesion molecule overexpression significantly predicted higher recurrence (hazard ratio=3.42; 95% confidence interval, 1.86-6.29; P<.001) and worse survival (hazard ratio=4.31; 95% confidence interval, 2.62-7.09; P<.001). Estrogen receptor positivity correlated significantly with reduced recurrence risk (hazard ratio=0.37; 95% confidence interval, 0.26-0.53) and improved survival (hazard ratio=0.22; 95% confidence interval, 0.17-0.29). Loss of progesterone receptor expression was associated with increased recurrence and poorer survival outcomes. Conversely, AT-rich interactive domain-containing protein 1A and catenin beta 1 mutations and STATHMIN1 overexpression did not significantly impact recurrence or survival outcomes. L1 cell adhesion molecule overexpression, estrogen receptor positivity, and progesterone receptor status demonstrate considerable prognostic relevance in no specific molecular profile endometrial cancer, warranting consideration as potential markers for improving patient management, including fertility-sparing approach.

Active surveillance of cervical intraepithelial neoplasia grade 2 is not associated with an increased risk of noncervical anogenital human papillomavirus–related cancer and precancer: a population-based cohort study

In recent years, many countries have implemented active surveillance (ie, leaving the lesion untreated) as an option in younger women with cervical intraepithelial neoplasia grade 2 instead of excisional treatment. This is mainly due to the high regression rates of cervical intraepithelial neoplasia grade 2 and the observed increased risk associated with excisional treatment. Women with a previous history of excisional treatment for cervical precancer are at an increased risk of subsequent anogenital cancer and precancer. For a full assessment of the benefits and harms of active surveillance for cervical intraepithelial neoplasia grade 2, we investigated the risk of noncervical anogenital cancers and precancers in women undergoing active surveillance. We aimed to investigate whether women undergoing active surveillance for cervical intraepithelial neoplasia grade 2 are at an increased risk of vulva, vaginal, or anal cancer and precancer compared to women treated with loop electrosurgical excision procedure. We conducted a nationwide population-based cohort study in Denmark. We included all female residents diagnosed with incident cervical intraepithelial neoplasia grade 2 at age 18 to 40 years from 1998 to 2020. The primary outcome was vulva, vaginal, or anal cancer or precancer. We stratified by age at cervical intraepithelial neoplasia grade 2 diagnosis (<30 years and ≥30 years), calendar year (1998-2012 and 2013-2020), and index cytology (nonhigh-grade and high-grade). As a secondary outcome, we considered low-grade lesions of the vulva, vagina, and anus. We used Cox regression to estimate hazard ratios of the outcomes with loop electrosurgical excision procedure as the reference group. We used inverse probability treatment weighting to calculate adjusted hazard ratios, considering age, calendar year, and index cytology as confounders. Overall, 27,505 women with cervical intraepithelial neoplasia grade 2 were included; 12,507 (45.5%) underwent active surveillance and 14,998 (54.5%) underwent loop electrosurgical excision procedure. A total of 162 women had a subsequent diagnosis of vulva, vaginal, or anal cancer or precancer. The cumulative risk after 10 years was 0.5% (95% confidence interval, 0.3-0.6). We found no difference in risk between women undergoing active surveillance and those having a loop electrosurgical excision procedure (adjusted hazard ratio, 1.00 [95% confidence interval, 0.71-1.40]). Similar findings were observed when stratifying by age, year of diagnosis, and index cytology. We found that the risk of low-grade lesions of the vulva, vagina, and anus was lower in women undergoing active surveillance than in women treated with loop electrosurgical excision procedure (adjusted hazard ratio, 0.75 [0.62-0.91]). Active surveillance for cervical intraepithelial neoplasia grade 2 is not associated with an increased risk of noncervical anogenital cancer and precancer compared to loop electrosurgical excision procedure. This finding contributes to the assessment of the benefits and harms of active surveillance and is useful for clinical counseling of women diagnosed with cervical intraepithelial neoplasia grade 2.

Research on intrauterine manipulators for endometrial cancer: attention to study-level characteristics

Reply to Research on intrauterine manipulators for endometrial cancer: attention to study-level characteristics

Effect of fragmentation of surgery and adjuvant treatment in high-grade nonendometrioid endometrial cancer: a population-based cohort study

Fragmented care (FC) occurs when patients receive treatment across several different hospitals. Regionalization of surgery for patients with high-grade endometrial cancer means that patients must travel longer distances to receive care; these patients often require adjuvant treatment after surgery. To determine whether the fragmentation of surgery and adjuvant treatment impacts survival in patients with high-grade nonendometrioid endometrial cancer. This population-based retrospective cohort study included patients diagnosed between 2003 and 2017 with high-grade nonendometrioid endometrial cancer who received adjuvant treatment postoperatively. Nonfragmented care was defined as receiving surgery and adjuvant treatment at the same institution. The primary outcome was overall survival. We identified 1795 patients, of whom 583 (32.5%) had FC. Patients with nonfragmented care were more likely to have had surgery by a gynecologic oncologist (92.4 vs 58.8%, P<.001), surgical staging (66.6 vs 44.8%, P<.001), and less travel for surgery (mean 30.8 km vs 93.7 km, P<.001). They were less likely to receive chemotherapy (26.3 vs 30%, P<.001) and chemoradiation (38.4 vs 41.3%, P<.001). Median survival was 9 years. There was no significant difference in overall survival between patients who received FC and nonfragmented care; 92.4% and 93.5% of the patients in the FC and nonfragmented care groups were treated at a specialized gynecologic oncology center for at least part of their treatment (surgery, adjuvant treatment, or both). We have previously shown that regionalization of surgery in high-grade endometrial cancer is associated with improved survival. Fragmentation of surgery and adjuvant treatment in this population does not have an adverse effect on survival. After receiving surgical treatment with a gynecologic oncologist, these patients may receive adjuvant treatment closer to home to decrease financial and travel burden.

Endometrial cancer in asymptomatic postmenopausal women: the importance of a rapid, nonharmful, and noninvasive diagnosis

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: a reply to unfounded concerns

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: look but do not overlook

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: a dutiful reply

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness: systematic review and diagnostic test accuracy meta-analysis

This study aimed to evaluate the risk of endometrial carcinoma and atypical endometrial hyperplasia in asymptomatic postmenopausal women concerning the endometrial thickness measured by stratified threshold categories used for performing subsequent endometrial sampling and histologic evaluation. MEDLINE, Scopus, ClinicalTrials.gov, SciELO, Embase, the Cochrane Central Register of Controlled Trials, LILACS, conference proceedings, and international controlled trials registries were searched without temporal, geographic, or language restrictions. Studies were selected if they had a crossover design evaluating the risk of atypical endometrial hyperplasia and endometrial carcinoma in postmenopausal asymptomatic women and calculated the diagnostic accuracy of transvaginal ultrasonography thresholds (at least 3.0 mm) confirmed by histopathologic diagnosis. This was a systematic review and diagnostic test accuracy meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy and Synthesizing Evidence from Diagnostic Accuracy Tests guidelines. Endometrial thickness thresholds were grouped as follows: from 3.0 to 5.9 mm; between 6.0 and 9.9 mm; between 10.0 and 13.9 mm; and ≥14.0 mm. Quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. Publication bias was quantified using the Deek funnel plot test. Coprimary outcomes were the risk of atypical endometrial hyperplasia or endometrial carcinoma according to the endometrial thickness and diagnostic accuracy of each threshold group. A total of 18 studies provided the data of 10,334 women who were all included in the final analysis. Overall, at an endometrial thickness threshold of at least 3.0 mm, the risk of atypical endometrial hyperplasia or endometrial carcinoma was increased 3-fold relative to women below the cutoff (relative risk, 3.77; 95% confidence interval, 2.26-6.32; I Both low and high endometrial thickness thresholds in postmenopausal asymptomatic women seem equally effective in detecting endometrial carcinoma and atypical endometrial hyperplasia. However, although using a 3.0 to 5.9 mm cutoff results in a lower specificity, the offsetting improvement in sensitivity may justify using this cutoff for further endometrial evaluation in patients with suspected endometrial malignancy.

Substantial variability in ovarian conservation at hysterectomy for endometrial hyperplasia

Although ovarian conservation at hysterectomy for benign gynecologic disease has demonstrated mortality benefit in young patients and this benefit may be sustained up to age 65 years, there is a scarcity of data regarding ovarian conservation in those with a diagnosis of endometrial hyperplasia, a premalignant uterine condition. This study aimed to examine patient, hospital, treatment, and histology characteristics related to ovarian conservation at the time of inpatient hysterectomy for endometrial hyperplasia. The Healthcare Cost and Utilization Project's National Inpatient Sample was retrospectively queried to examine patients aged ≤65 years with endometrial hyperplasia who had inpatient hysterectomy from January 2016 to December 2019. The exclusion criteria included concurrent gynecologic malignancy, adnexal pathology, and lymphadenectomy. Cases were grouped by adnexal surgery status (ovarian conservation or oophorectomy). A multivariable binary logistic regression model was used to identify independent characteristics for ovarian conservation. A classification tree was constructed with recursive partitioning analysis to examine utilization patterns of ovarian conservation. Overall, 3105 patients (31.1%) underwent ovarian conservation at hysterectomy among 9975 patients. The utilization of ovarian conservation decreased gradually until age 45 years and then markedly decreased by age 52 years (63.3%-15.3%; P<.001). In a multivariable analysis, younger age, non-White, urban nonteaching centers, and vaginal hysterectomy were associated with increased utilization of ovarian conservation, whereas endometrial hyperplasia with atypia, obesity, comorbidity, large bed capacity centers, and Midwest and South regions were associated with decreased utilization of ovarian conservation (all, P<.05). A classification tree identified 17 utilization patterns for ovarian conservation, ranging from 7.8% to 100.0% (absolute rate difference, 92.2%). The utilization of ovarian conservation at the time of inpatient hysterectomy in patients undergoing surgical management for endometrial hyperplasia started decreasing in their mid-40s and seemed to occur earlier than in benign hysterectomy. There was substantial variability in ovarian conservation at the time of hysterectomy for endometrial hyperplasia based on patient, hospital, surgical, and histology factors, suggesting the possible benefit of clinical practice guidelines for ovarian conservation in this population.

Ovarian conservation for young women with early-stage, low-grade endometrial cancer: a 2-step schema

In 2020, endometrial cancer continues to be the most common gynecologic malignancy in the United States. The majority of endometrial cancer is low grade, and nearly 1 of every 8 low-grade endometrial cancer diagnoses occurs in women younger than 50 years with early-stage disease. The incidence of early-stage, low-grade endometrial cancer is increasing particularly among women in their 30s. Women with early-stage, low-grade endometrial cancer generally have a favorable prognosis, and hysterectomy-based surgical treatment alone can often be curative. In young women with endometrial cancer, consideration of ovarian conservation is especially relevant to avoid both the short-term and long-term sequelae of surgical menopause including menopausal symptoms, cardiovascular disease, metabolic disease, and osteoporosis. Although disadvantages of ovarian conservation include failure to remove ovarian micrometastasis (0.4%-0.8%), gross ovarian metastatic disease (4.2%), or synchronous ovarian cancer (3%-5%) at the time of surgery and the risk of future potential metachronous ovarian cancer (1.2%), ovarian conservation is not negatively associated with endometrial cancer-related or all-cause mortality in young women with early-stage, low-grade endometrial cancer. Despite this, utilization of ovarian conservation for young women with early-stage, low-grade endometrial cancer remains modest with only a gradual increase in uptake in the United States. We propose a framework and strategic approach to identify young women with early-stage, low-grade endometrial cancer who may be candidates for ovarian conservation. This evidence-based schema consists of a 2-step assessment at both the preoperative and intraoperative stages that can be universally integrated into practice.

The undisputed strategy of “no touch”

Endometrial polyps

Disparities in adjuvant treatment of high-grade endometrial cancer in the Medicare population

Black women experience worse survival effects with high-grade endometrial cancer. Differences in adjuvant treatment have been proposed to be major contributors to this disparity. However, little is known about the differences in type or timing of adjuvant treatment as it relates to race and ethnicity in the Medicare population. This study aimed to examine patterns of adjuvant therapy and survival for non-Hispanic Black women vs non-Hispanic White women and Hispanic women who have undergone surgery for high-grade endometrial cancer in the Medicare population. We used the Medicare-linked Surveillance, Epidemiology, and End Results database to identify women who underwent surgery as a primary treatment for uterine grade 3 endometrioid adenocarcinoma, carcinosarcoma, clear-cell carcinoma, or serous carcinoma between the years 2000 and 2015. Women who did not identify as White or Black race or Hispanic ethnicity were excluded. Multinomial logistic regression was used to estimate odds ratios and 95% confidence intervals for receiving a treatment delay or not receiving adjuvant treatment (compared with those who received adjuvant treatment within 12 weeks) adjusted for clinical and demographic characteristics. Overall survival was stratified by race and ethnicity, route of surgery, operative complications, and type and timing of adjuvant therapy, which were analyzed using the Kaplan-Meier method. Cox proportional-hazards regression was used to estimate the hazard ratio of death by race and ethnicity adjusted for known predictors and surgical outcomes and adjuvant therapy patterns. A total of 12,201 women met the study inclusion criteria. Non-Hispanic Black patients had a significantly worse 5-year overall survival than Hispanic and non-Hispanic White patients (30.9 months vs 51.0 months vs 53.6 months, respectively). Approximately 632 of 7282 patients (8.6%) who received adjuvant treatment experienced a treatment delay. Delay in treatment of ≥12 weeks was significantly different by race and ethnicity (P=.034), with 12% of Hispanic, 9% of non-Hispanic Black, and 8% of non-Hispanic White women experiencing a delay. After adjustment for the number of complications, age, histology (endometrioid vs nonendometroid), International Federation of Gynecology and Obstetrics stage, marital status, comorbidity count, surgical approach, lymph node dissection, and urban-rural code, Hispanic women had a 71% increased risk of treatment delay (odds ratio, 1.71; 95% confidence interval, 1.23-2.38) for all stages of disease. In the same model, non-Hispanic Black race was independently predictive of decreased use of adjuvant treatment for the International Federation of Gynecology and Obstetrics stage II and higher (odds ratio, 1.32; 95% confidence interval, 1.04-1.68). Non-Hispanic Black race, number of perioperative complications, and nonendometrioid histology were predictive of worse survival in univariate models. Treatment delay was not independently predictive of worse 1- or 5-year survival at any stage. Non-Hispanic Black race was predictive of worse 5-year survival across all stages and was associated with omission of adjuvant treatment in International Federation of Gynecology and Obstetrics stage II or higher high-grade endometrial cancer. In unadjusted analyses, patients who experience treatment omission or delay experienced poorer overall survival, but these factors were not independently associated in multivariate analyses. This study suggests that race and ethnicity are independently associated with the type and timing of adjuvant treatment in patients with high-grade endometrial cancer. Further efforts to identify specific causes of barriers to care and timely treatment are imperative.

Uterine manipulator in endometrial cancer: we are still far from the answer

Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics

A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.

Primary cytoreductive surgery for advanced stage endometrial cancer: a systematic review and meta-analysis

Endometrial cancer uncommonly presents at an advanced stage and little prospective evidence exists to guide the management thereof. We aimed to summarize the evidence about primary cytoreductive surgery in the treatment of advanced stage endometrial cancer. MEDLINE, Embase, and Scopus databases were searched from inception to September 11, 2020, using search terms representing the themes "endometrial cancer," "advanced stage," and "primary cytoreductive surgery." We included full-text, English reports that included ≥10 patients undergoing primary cytoreductive surgery for advanced stage endometrial cancer and that reported on the outcomes of primary cytoreductive surgery and survival rates based on the residual disease burden. Two reviewers independently screened the studies and with disagreements between the reviewers resolved by a third reviewer. Data were extracted using a standardized form. The percentage of cases reaching maximal (no gross residual disease) and optimal (<1 cm or <2 cm residual disease) cytoreduction were assessed by summing binomials proportions, and the association with survival was assessed using an inverse variance-weighted meta-analysis of logarithmic hazard ratios. From 1219 unique records identified, 34 studies were selected for inclusion. Studies consisted of single or multi-institutional cohorts of patients collected over a period of 6 to 24 years and included various mixes of histologies (endometrioid, serous, clear cell, and carcinosarcoma) and disease stages (III or IV). In a meta-analysis of the extent of residual disease after primary cytoreductive surgery, we found that 52.1% of cases reached no gross residual disease status (n=18 studies; 1329 patients) and 75% reached <1 cm residual disease status (n=27 studies; 2343 patients). The proportion of cytoreduction for both thresholds was lower for studies of stage IV vs stage III to IV disease (41.4% vs 69.8% for no gross residual disease; 63.2% vs 82.2% for <1 cm residual disease) but did not vary notably by histology. In a meta-analysis of the reported hazard ratios, submaximal (any gross residual disease vs no gross residual disease) and suboptimal (≥1 cm vs <1 cm) cytoreduction thresholds were associated with worse progression-free survival (submaximal hazard ratio, 2.16; 95% confidence interval, 1.45-3.21; I Among cases of advanced stage endometrial cancer undergoing primary cytoreductive surgery, a significant proportion of patients are left with residual disease, which is associated with worse survival outcomes. Further investigations about the roles of neoadjuvant chemotherapy and primary cytoreductive surgery in prospective trials is warranted in this population.

Proposal of an endometrial cancer staging schema with stage-specific incorporation of malignant peritoneal cytology

Outcomes after the regionalization of care for high-grade endometrial cancers: a population-based study

In June 2013, Ontario Health (Cancer Care Ontario), the agency responsible for advancing cancer care in Ontario, Canada, published practice guidelines recommending that gynecologic oncologists at tertiary care centers manage the treatment of patients with high-grade endometrial cancers. This study examines the effects of this regionalization of care on patient outcomes. This study aimed to evaluate the impact of the regionalization of surgery for high-grade endometrial cancer on patient and treatment outcomes. In this retrospective cohort study, patients diagnosed with nonendometrioid high-grade endometrial cancer from 2003 to 2017 were identified using province-wide administrative databases. To allow 6 months for knowledge translation, 2 periods were defined, with January 1, 2014, as the cutoff. Methods for segmented regression were used to test the effect of the guidelines. Multivariable Cox proportional hazards regression was used to evaluate whether regionalization of care had an impact on patient survival. There were 3518 patients with nonendometrioid high-grade endometrial cancer identified. The case mix as represented by patient comorbidities and the disease stage distribution did not differ significantly between the 2 regionalization periods. There was a significant increase (69%-85%; P<.001) in the proportion of primary surgeries performed by gynecologic oncologists after regionalization, which was not explained by secular trends. After regionalization, the proportion of patients who had surgical staging (50%-63%; P<.001) and the proportion of patients who received adjuvant treatment (65%-71%; P<.001) increased significantly. After adjusting for age, stage, and comorbidities, there was a decrease in the hazard of mortality (hazard ratio, 0.85 [95% confidence interval, 0.73-0.99]; P=.04) after regionalization. The publication of a regionalization policy for the treatment of high-grade endometrial cancers in Ontario led to an increase in the proportion of surgeries performed by gynecologic oncologists. This also translated into a significant improvement in patient survival.

Endometrial biomarkers in premenopausal women with obesity: an at-risk cohort

Obesity is a well-known risk factor for endometrial cancer, but the mechanisms of obesity-related carcinogenesis are not well defined, particularly for premenopausal women. With the continuing obesity epidemic, increases in the incidence of endometrial cancer and a younger age of diagnosis are often attributed to a hyperestrogenic state created by hormone production in adipose tissue, but significant knowledge gaps remain. The balance of estrogen-responsive signals has not been defined in the endometrium of premenopausal women with obesity, where obesity may not create hyperestrogenism in the context of ovaries being the primary source of estrogen production. Obesity is associated with a state of low-grade, chronic inflammation that can promote tumorigenesis, and it is also known that hormonal changes alter the immune microenvironment of the endometrium. However, limited research has been conducted on endometrial immune-response changes in women who have an increased risk for cancer due to obesity. Endometrial estrogen-regulated biomarkers, previously shown to be dysregulated in endometrial cancer, were evaluated in a cohort of premenopausal women to determine if obesity is associated with differences in the biomarker expression levels, which might reflect an altered risk of developing cancer. The expression of a multiplexed panel of immune-related genes was also evaluated for expression differences related to obesity. Premenopausal women with a body mass index of ≥30 kg/m In addition to known systemic metabolic differences, histologically normal endometria from women with obesity showed a decrease in gene expression of progesterone receptor (P=.0027) and the estrogen-induced genes retinaldehyde dehydrogenase 2 (P=.008), insulin-like growth factor 1 (P=.016), and survivin (P=.042) when compared with women without obesity. The endometrial biomarkers insulin-like growth factor 1, survivin, and progesterone receptor remained statistically significant in multivariate linear regression models. In contrast, women with obesity and Lynch syndrome had an increased expression of insulin-like growth factor 1 (P=.017). There were no differences in endometrial proliferation, and limited endometrial immune differences were observed. When comparing premenopausal women with and without obesity in the absence of endometrial pathology or an inherited cancer risk, the expression of the endometrial biomarkers does not reflect a local hyperestrogenic environment, but it instead reflects a decreased cancer risk profile that may be indicative of a compensated state. In describing premenopausal endometrial cancer risk, it may be insufficient to attribute a high-risk state to obesity alone; further studies are warranted to evaluate individualized biomarker profiles for differences in the hormone-responsive signals or immune response. In patients with Lynch syndrome, the endometrial biomarker profile suggests that obesity further increases the risk of developing cancer.

Prospective phase II trial of levonorgestrel intrauterine device: nonsurgical approach for complex atypical hyperplasia and early-stage endometrial cancer

The incidence of complex atypical hyperplasia and early-stage endometrioid endometrial cancer is increasing, in part owing to the epidemic of obesity, which is a risk factor tightly linked to the development of endometrial hyperplasia and cancer. The standard upfront treatment for complex atypical hyperplasia and early-stage endometrial cancer is hysterectomy. However, nonsurgical treatment of early-stage endometrial neoplasia may be necessary owing to medical comorbidities precluding surgery or desired future fertility. This study aimed to evaluate the efficacy of the levonorgestrel intrauterine device to treat complex atypical hyperplasia and grade 1 endometrioid endometrial carcinoma. A single-institution, single-arm, phase II study of the levonorgestrel intrauterine device (52 mg levonorgestrel, Mirena) was conducted in patients with complex atypical hyperplasia or grade 1 endometrioid endometrial cancer. The primary endpoint was pathologic response rate at 12 months, including complete or partial response. Quality of life and toxicity were assessed. Molecular analyses for proliferation markers, hormone-regulated genes, and wingless-related integration site pathway activation were performed at baseline and 3 months. A total of 57 patients were treated (21 endometrial cancer, 36 complex atypical hyperplasia). The median age was 48.0 years, and the median body mass index was 45.5 kg/m The levonorgestrel intrauterine device has a substantial activity in complex atypical hyperplasia and grade 1 endometrioid endometrial cancer, with a modest proportion demonstrating upfront progesterone resistance. Potential biomarkers were identified that may correlate with resistance to therapy; further exploration is warranted.

Validation of an enhanced recovery after surgery protocol in gynecologic surgery: an Italian randomized study

The enhanced recovery after surgery concept, which was introduced 20 years ago, is based on a multimodal approach to improve the functional rehabilitation of patients after surgery. This study aimed to validate an enhanced recovery after surgery protocol in gynecologic surgery for both benign and malignant diseases (endometrial cancer and advanced ovarian cancer) and to measure the adherence to the enhanced recovery after surgery protocol items in a randomized trial setting. In this trial (NCT03347409), we randomly assigned patients to undergo standard perioperative care or enhanced recovery after surgery protocol. The primary outcome is a shorter length of stay in favor of the enhanced recovery after surgery protocol. Secondary outcomes include measurement of adherence to the enhanced recovery after surgery protocol items: comparison of postoperative pain, vomiting, and nausea; anesthesiologic and surgical complications up to 30 days after surgery; rate of readmissions; the time to event in hours for bowel movements, flatus, drinking, hunger, eating, and walking; and the quality of recovery using a validated questionnaire (QoR-15). Finally, we explored the length of stay in the prespecified subgroups at randomization, based on the type of surgical access and gynecologic disease. A total of 168 women were available for analysis: 85 women (50.6%) were assigned to the standard perioperative care group, and 83 women (49.4%) were assigned to the enhanced recovery after surgery protocol group. The 2 groups were similar for age, body mass index, comorbidities, anesthesiological risk, smoking habits, surgical access, and complexity of surgical procedures. Seventy-two patients (42.9%) underwent surgery for benign disease, 48 (28.6%) for endometrial cancer, and 48 (28.6%) for ovarian cancer. Women in the enhanced recovery after surgery protocol group had a shorter length of stay (median: 2 [interquartile range, 2-3] vs 4 [interquartile range, 4-7] days; P<.001). A decreased rate of postoperative complications was noted for the enhanced recovery after surgery protocol group, as well as an earlier time to occur for all the events. Mean adherence to protocol items was 84.8% (95% confidence interval, 79.7-89.8), and we registered a better satisfaction in the enhanced recovery after surgery protocol group. The shortening of the length of stay was confirmed also in the prespecified subgroup analysis. Application of the enhanced recovery after surgery protocol in gynecologic surgery translated to a shorter length of stay regardless of surgical access and type of gynecologic disease. Adherence to the enhanced recovery after surgery protocol items in the setting of a randomized trial was high.

Toward a risk-based approach to evaluate and manage abnormal uterine bleeding

A cesarean delivery sequela:

Impact of quality of care on racial disparities in survival for endometrial cancer

Black women experience poorer survival compared with white women across all endometrial cancer stages and histologies. The incidence of endometrial cancer is 30% lower in black women compared with white women, yet mortality is 80% higher in black women. Differences in adherence to evidence-based guidelines have been proposed to be major contributors to this disparity. We examined whether adherence to evidence-based treatment recommendations for endometrial cancer could mitigate survival disparities between black and white women. The National Cancer Database was used to identify women with endometrial cancer treated from 2004 through 2016. We established 5 evidence-based quality metrics based on review of primary literature and accepted guidelines: surgical treatment within 6 weeks of diagnosis (Q1), use of minimally invasive surgery (stage I-IIIC; Q2), pelvic nodal assessment (high-risk tumors; Q3), adjuvant radiation (high intermediate risk; Q4), and systemic chemotherapy (stage III-IV; Q5). The rates of 30 and 90 day mortality and 5 year survival were compared between black and white women. To determine the influence of quality on outcomes, we compared outcomes among perfectly adherent black and white women with stage I and III endometrial cancer. We identified 310,208 women including 35,035 (11.3%) black women and 275,173 (88.3%) white women. Black women were less likely than white women to receive Q1 (65.8 vs 75.6%), Q2 (58.5 vs 72.9%), Q3 (71.3 vs 74.2%), and Q5 (72.7 vs 73.2%) (P < .05 for all). Adherence to each quality metrics was associated with improved survival. Among women with stage I disease, perfect adherence to the relative quality metrics was seen in 53.1% of white and 41.5% of black women. Among perfectly adherent stage I patients, outcomes in black women improved relative to unselected black women; however, they still experienced higher risk of 30 day (adjusted relative risk, 2.25; 95% confidence interval, 1.30-3.90), 90 day (adjusted relative risk, 1.84; 95% confidence interval, 1.23-2.76), and 5 year mortality (adjusted hazard ratio, 1.42; 95% confidence interval, 1.26-1.59) compared with similar white women. Among women with stage III tumors, perfect adherence to the relative quality metrics was seen in 56.6% of white and 44.1% of black women. Perfectly adherent black women with stage III disease had improved outcomes but remained at increased risk of 30 day (adjusted relative risk, 1.86; 95% confidence interval, 1.01-3.44) and 5 year mortality (adjusted hazard ratio, 1.35; 95% confidence interval, 1.22-1.50) compared with white women. Black women are less likely than white women with endometrial cancer to receive evidence-based care. However, receipt of evidence-based care mitigates but does not eliminate racial disparities in outcomes and black women remain at greater risk of death from endometrial cancer.

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study

Several studies have suggested that endometriosis is associated with an increased risk of ovarian cancer, especially for the clear-cell and endometrioid subtypes. However, previous studies lack sufficient power or diagnostic certainty. The objective of the study was to assess the association between histologically proven endometriosis and ovarian cancer in a large population-based cohort study. We identified 131,450 women with a histological diagnosis of endometriosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). For the control cohort 132,654 women with a benign dermal nevus were matched on age and inclusion year with the endometriosis cases. Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved. Incidence rate ratios were estimated for ovarian cancer and its subtypes for the whole follow-up period as well as for women with more than 1 person-year at risk. We found a crude incidence rate ratio of 4.79 (95% confidence interval, 4.33-5.31) and an age-adjusted incidence rate ratio of 7.18 (95% confidence interval, 6.17-8.36) for ovarian cancer overall. Endometrioid and clear-cell ovarian cancer had the highest age-adjusted incidence rate ratio of 29.06 (95% confidence interval, 20.66-40.87) and 21.34 (95% confidence interval, 14.01-32.51), respectively. Median age at ovarian cancer diagnosis was 56 years (interquartile range, 49-63) for the endometriosis cohort and 60 years (interquartile range, 53-67) for the nevus cohort, (P < .05). After excluding women with less than 1 person-year at risk following an endometriosis diagnosis, we found a crude incidence rate ratio of 1.04 (95% confidence interval, 0.91-1.19) and an age-adjusted incidence rate ratio of 1.08 (95% confidence interval, 0.87-1.35) for ovarian cancer overall. However, statistically significant age-adjusted incidence rate ratios of 2.29 (95% confidence interval, 1.24-4.20) for clear-cell ovarian cancer and 2.56 (95% confidence interval, 1.47-4.47) for endometrioid ovarian cancer were found. A significantly higher incidence of clear-cell and endometrioid ovarian cancer was found in women with histologically proven endometriosis. Additionally, we found an increased incidence of all ovarian cancer subtypes in histologically proven endometriosis; however, in many of these women, endometriosis and ovarian cancer were diagnosed synchronously after the average menopausal age, which may suggest that the risk of ovarian cancer in endometriosis patients remains, even when clinical endometriosis symptoms are no longer present.

Preoperative predictors of endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia or complex atypical hyperplasia

Endometrial intraepithelial neoplasia, also known as complex atypical hyperplasia, is a precancerous lesion of the endometrium associated with a 40% risk of concurrent endometrial cancer at the time of hysterectomy. Although a majority of endometrial cancers diagnosed at the time of hysterectomy for endometrial intraepithelial neoplasia are low risk and low stage, approximately 10% of patients ultimately diagnosed with endometrial cancers will have high-risk disease that would warrant lymph node assessment to guide adjuvant therapy decisions. Given these risks, some physicians choose to refer patients to a gynecologic oncologist for definitive management. Currently, few data exist regarding preoperative factors that can predict the presence of concurrent endometrial cancer in patients with endometrial intraepithelial neoplasia. Identification of these factors may assist in the preoperative triaging of patients to general gynecology or gynecologic oncology. To determine whether preoperative factors can predict the presence of concurrent endometrial cancer at the time of hysterectomy in patients with endometrial intraepithelial neoplasia; and to describe the ability of preoperative characteristics to predict which patients may be at a higher risk for lymph node involvement requiring lymph node assessment at the time of hysterectomy. We conducted a retrospective cohort study of women undergoing hysterectomy for pathologically confirmed endometrial intraepithelial neoplasia from January 2004 to December 2015. Patient demographics, imaging, pathology, and outcomes were recorded. The "Mayo criteria" were used to determine patients requiring lymphadenectomy. Unadjusted associations between covariates and progression to endometrial cancer were estimated by 2-sample t-tests for continuous covariates and by logistic regression for categorical covariates. A multivariable model for endometrial cancer at the time of hysterectomy was developed using logistic regression with 5-fold cross-validation. Of the 1055 charts reviewed, 169 patients were eligible and included. Of these patients, 87 (51.5%) had a final diagnosis of endometrial intraepithelial neoplasia/other benign disease, whereas 82 (48.5%) were ultimately diagnosed with endometrial cancer. No medical comorbidities were found to be strongly associated with concurrent endometrial cancer. Patients with endometrial cancer had a thicker average endometrial stripe compared to the patients with no endometrial cancer at the time of hysterectomy (15.7 mm; standard deviation, 9.5) versus 12.5 mm; standard deviation, 6.4; P = .01). An endometrial stripe of ≥2 cm was associated with 4.0 times the odds of concurrent endometrial cancer (95% confidence interval, 1.5-10.0), controlling for age. In all, 87% of endometrial cancer cases were stage T1a (Nx or N0). Approximately 44% of patients diagnosed with endometrial cancer and an endometrial stripe of ≥2 cm met the "Mayo criteria" for indicated lymphadenectomy compared to 22% of endometrial cancer patients with an endometrial stripe of <2 cm. Endometrial stripe thickness and age were the strongest predictors of concurrent endometrial cancer at time of hysterectomy for endometrial intraepithelial neoplasia. Referral to a gynecologic oncologist may be especially warranted in endometrial intraepithelial neoplasia patients with an endometrial stripe of ≥2 cm given the increased rate of concurrent cancer and potential need for lymph node assessment.

Effect of regionalization of endometrial cancer care on site of care and patient travel

Complex oncologic surgeries, including those for endometrial cancer, increasingly have been concentrated to greater-volume centers, owing to previous research that has demonstrated associations between greater surgical volume and improved outcomes. There is a potential for concentration of care to have unwanted consequences, including cost burden, delayed treatment, patient dissatisfaction, and possibly worse clinical outcomes, especially for more vulnerable populations. To describe changes in site of care for patients with endometrial cancer in New York State and to determine whether the distance women traveled for hysterectomy has changed over time. We used the New York Statewide Planning and Research Cooperative System to identify women with endometrial cancer who underwent hysterectomy from 2000 to 2014. Demographic and clinical data as well as hospital data were collected. Trends in travel distance (straight-line distance) were analyzed within all hospital referral regions and differences in travel distance over times and across sociodemographic characteristics analyzed. We identified 41,179 subjects. The number of hospitals and surgeons performing hysterectomy decreased across all hospital referral regions over time. The decline in the number of hospitals caring for women with endometrial cancer ranged from -16.7% in Syracuse (12 to 10 hospitals) to -76.5% in Rochester (17 to 4 hospitals). Similarly, the percentage of surgeons within a given hospital referral region operating on women declined from -45.2% in Buffalo (84-46 surgeons) to -77.8% in Albany (72 to 16 surgeons). The median distance to the index hospital for patients increased in all Hospital Referral Regions. For residents in Binghamton, median travel distance increased by 46.9 miles (95% confidence interval, 33.8-60.0) whereas distance increased in Elmira by 19.7 miles (95% confidence interval, 7.3-32.1) and by 12.4 miles (95% confidence interval, 6.4-18.4) in Albany. For residents of Binghamton and Albany, there was a greater than 100% increase in distance traveled over the 15-year time period, with increases of 551.8% (46.9 miles; 95% confidence interval, 33.8-60.0 miles) and 102.5% (12.4 miles; 95% confidence interval, 6.4-18.4 miles), respectively. Travel distance increased for all races and regardless of insurance status but was greatest for white patients and those with private insurance (P<.0001 for both). The number of surgeons and hospitals caring for women with endometrial cancer in New York State has decreased, whereas the distance that patients travel to receive care has increased over time.

Use of prophylactic closed incision negative pressure therapy is associated with reduced surgical site infections in gynecologic oncology patients undergoing laparotomy

Surgical site infection after surgery for gynecologic cancer increases morbidity. Prophylactic closed incision negative pressure therapy has shown promise in reducing infectious wound complications across many surgical disciplines. This study aimed to determine whether closed incision negative pressure therapy is associated with reduced surgical site infections in gynecologic oncology patients undergoing laparotomy compared with standard dressings. This was a retrospective case-control study of patients undergoing laparotomy for known or suspected gynecologic cancer from Jan. 1, 2017, to Feb. 1, 2020. Patients were matched in a 1:3 ratio (closed incision negative pressure therapy to standard dressing) by body mass index, age, diabetes, bowel surgery, smoking, and steroid use. Surgical site infection was defined according to the Centers for Disease Control and Prevention. Multivariable logistic regression using backward selection was performed. Of the 1223 eligible patients undergoing laparotomy, 64 (5.2%) received closed incision negative pressure therapy dressings and were matched to 192 (15.7%) controls. There were no differences in medical comorbidities (P>.05), site or stage of malignancy (P>.05), duration of surgery (P=.82), or surgical procedures (P>.05). Use of closed incision negative pressure therapy was associated with reduction in all adverse wound outcomes (20.3% vs 40.1%; P<.001). In particular, closed incision negative pressure therapy was associated with a significant reduction in both superficial incisional surgical site infections (9.4% vs 29.7%; P<.001) and deep incisional surgical site infections (0.0% vs 6.8%; P=.04). In multivariable analysis, use of closed incision negative pressure therapy was associated with significant reduction in the incidence of superficial incisional infections alone (odds ratio, 0.29; 95% confidence interval, 0.12-0.73; P=.008) and both superficial and deep incisional infections (odds ratio, 0.29; 95% confidence interval, 0.12-0.71; P=.007). Use of prophylactic closed incision negative pressure therapy after laparotomy in gynecologic oncology patients was found to be associated with reduced superficial incisional and deep incisional infections compared with standard dressings. Furthermore, closed incision negative pressure therapy was associated with reduction in all other adverse wound outcomes. Closed incision negative pressure therapy may be considered for surgical site infection prevention in high-risk gynecologic oncology patients undergoing laparotomy.

Adherence to risk-reducing salpingo-oophorectomy guidelines among gynecologic oncologists compared to general gynecologists

Risk-reducing bilateral salpingo-oophorectomy reduces mortality from high-grade serous carcinoma in patients with hereditary breast and ovarian cancer associated gene mutations. Ideal surgical management includes 5 steps outlined in 2005 by the Society of Gynecologic Oncology and the American College of Obstetricians and Gynecologists. In addition, it is recommended that pathologic examination include serial sectioning of specimens. In practice, risk-reducing salpingo-oophorectomy is performed by both gynecologic oncologists and general gynecologists. To ensure optimal detection of occult malignancy, standardized adherence to outlined guidelines is necessary. This study aimed to evaluate the adherence to optimal surgical and pathologic examination guidelines and to compare the rate of occult malignancy at the time of surgery between 2 provider types. Institutional review board exemption was obtained. A retrospective review of patients undergoing risk-reducing bilateral salpingo-oophorectomy without hysterectomy from October 1, 2015, to December 31, 2020, at 3 sites within a healthcare system was conducted. The inclusion criteria included age ≥18 years and a documented indication for surgery being a mutation in BRCA1 or BRCA2 or a strong family history of breast and/or ovarian cancer. Compliance with 5 surgical steps and pathologic specimen preparation was based on medical record documentation. Multivariable logistic regression was used to determine differences in adherence between provider groups and surgical and pathologic examination guidelines. A P value of .025). Overall, 5 patients (2.70%) had occult malignancy diagnosed at the time of risk-reducing surgery, with all surgeries performed by general gynecologists. Our results demonstrated greater compliance with surgical guidelines for risk-reducing bilateral salpingo-oophorectomy in gynecologic oncologists than in general gynecologists. No considerable difference was determined between the 2 provider types in adherence to pathologic guidelines. Our findings demonstrated a need for institution-wide protocol education and implementation of standardized nomenclature to ensure provider adherence to evidence-based guidelines.

Ultrasound characteristics of early-stage high-grade serous ovarian cancer

Survival from ovarian cancer is strongly dependent on the stage at diagnosis. Therefore, when confronted with a woman with an isolated adnexal mass, clinicians worry about missing the opportunity to detect cancer at an early stage. High-grade serous ovarian cancers account for 80% of ovarian cancer deaths, largely because of their tendency to be diagnosed at a late stage. Among adnexal masses, large size and the presence of solid areas on ultrasound examination have been found to be associated with cancer, but it is unclear whether these characteristics identify early-stage cases. This study aimed to evaluate the ultrasound findings associated with clinically detected early-stage high-grade serous ovarian cancer. This was a retrospective cohort study of women diagnosed with stage I or II high-grade serous ovarian or fallopian tube cancer measuring at least 1 cm at pathology from 2007 to 2017. Preoperative ultrasound examinations were independently reviewed by 3 radiologists. Adnexal masses were scored for size and volume; overall appearance; presence, thickness, and vascularity of septations; morphology and vascularity of other solid components; and degree of ascites. Characteristics were compared between masses of <5 cm and larger masses and between stage I and stage II cases. Interobserver variability was assessed. Among 111 women identified, 4 had bilateral ovarian involvement, for a total of 115 adnexal masses characterized by ultrasound examination. The mean age at diagnosis was 61.8 years (range, 42-91 years). The median mass size was 9.6 cm (range, 2.2-23.6 cm) with 87% of cases having a mass size of ≥5 cm. A mixed cystic and solid appearance was most common (77.4%), but a completely solid appearance was more frequently seen for tumors of <5 cm compared with larger tumors (26.7% vs 13.0%). Solid components other than septations were seen in 97.4% of cases. The characteristics of stage I and II cases were similar other than ascites, which was more commonly seen in stage II cases (18.0% vs 3.1%, respectively). Interobserver concordance was high for size and volume measurements (correlation coefficients, 0.96-0.99), with moderate agreement observed across the other ultrasound characteristics (Fleiss kappa, 0.45-0.58). In this community-based cohort, early-stage high-grade serous cancers rarely presented as masses of <5 cm or masses without solid components other than septations. Our findings provide additional support for the observation of small masses without solid areas on ultrasound examination.

Cesarean radical hysterectomy for cervical cancer in the United States: a national study of surgical outcomes

Peer influence on physicians in adopting opportunistic salpingectomy at the time of hysterectomy

Since professional societies recommended counseling patients about opportunistic salpingectomy for ovarian cancer risk reduction, use of opportunistic salpingectomy has increased overall. However, physicians varied in their adoption of this new cancer prevention strategy. To examine peer influence among physicians as a possible factor affecting their adoption of opportunistic salpingectomy at the time of hysterectomy. Using insurance claims data from the Blue Cross Blue Shield Axis database across the United States, we identified female patients aged 18 to 49 who underwent an inpatient hysterectomy in 2019 to 2022. The outcome of interest was opportunistic salpingectomy, defined as complete removal of both (or the remaining) fallopian tubes without concurrent removal of the ovaries. We identified peer relationships among physicians based on whether 2 physicians billed for at least 2 of the same patients among insurance claims in 2017 to 2018. Then for each index physician performing inpatient hysterectomy in the 2019 to 2022 sample, we measured the rate of opportunistic salpingectomy among inpatient hysterectomies performed by all of their peer physicians in 2017 to 2018 (baseline). A multivariable regression analysis was used to examine whether an index physician's baseline exposure to peer physicians' opportunistic salpingectomy rate was associated with the subsequent use of opportunistic salpingectomy among their own patients in 2019 to 2022. Among 3373 patients who underwent inpatient hysterectomy in 2019 to 2022 (operated on by 1528 index physicians), 1871 (55.5%) received opportunistic salpingectomy. The rate of opportunistic salpingectomy was higher among patients whose index physician had exposure to peer physicians with the highest or second highest quartile of baseline opportunistic salpingectomy rate (64.5% and 59.6%, respectively), compared to those with peer physicians in the lowest quartile of baseline opportunistic salpingectomy rate (44.0%) (P<.001). After adjusting for surgical indication, surgical route, and other patient/physician characteristics, having peer physicians in the highest and second highest quartile of baseline opportunistic salpingectomy rate was associated with a 1.99 (95% confidence interval, 1.46-2.71) times and 1.64 (95% confidence interval, 1.21-2.22) times higher odds of receiving opportunistic salpingectomy, respectively. Sharing patients with other physicians who had high utilization of opportunistic salpingectomy was associated with an increased likelihood of an index physician subsequently using opportunistic salpingectomy at the time of hysterectomy. Future efforts to promote opportunistic salpingectomy use may explore the potential benefit of strategies leveraging physician peer influence.

Uterine cancer diagnosis at age 65: onset of Medicare eligibility and impact of Medicaid expansion

Uterine cancer, for which diagnosis is based on evaluation of symptoms, most commonly postmenopausal bleeding, is one of the few cancers in the United States with rising incidence and mortality. Inability to access diagnostic services due to lack of insurance coverage may lead to delayed diagnosis and inferior outcomes. The aim of the study was to examine whether the onset of Medicare eligibility at age 65 was associated with a spike in the incidence of uterine cancer and whether this association was attenuated by Medicaid expansion through the Affordable Care Act. This ecological study used cancer registry data from the Surveillance, Epidemiology, and End Results program to estimate the incidence rate of uterine cancer among women aged 55 to 74 from 2000 to 2021 in the United States. Second order polynomial modeling was used to fit the association between age (in single years) and incidence rate at the population level while excluding age 65 to identify the expected incidence rate at age 65 in the absence of a spike. The expected uterine cancer incidence rate at age 65 was generated from the model and compared to the observed rate at age 65 in the overall sample. Similar analyses were also conducted further stratified by stage, race and ethnicity, pre-Affordable Care Act (2004-2013) versus post-Affordable Care Act (2014-2021) period and states' Medicaid expansion status. In the overall sample, the observed uterine cancer incidence rate at age 65 was 108.2 cases per 100,000 woman-years (95% confidence interval, 106.4 to 110.1), which exceeded the expected rate projected from the polynomial model (102.5; 95% confidence interval, 101.4-103.5). A similar pattern was observed in analysis stratified by stage at diagnosis and by race and ethnicity. The spike in incidence at age 65 diminished in Medicaid expansion states in the post-Affordable Care Act period but persisted in nonexpansion states. Onset of Medicare eligibility at age 65 was associated with a spike in uterine cancer diagnoses, which appeared to be mitigated by Medicaid expansion. These findings underscore the importance of insurance coverage in facilitating timely uterine cancer diagnoses.

Cost of ovarian cancer by the phase of care in the United States

Ovarian cancer is associated with delayed diagnosis and poor survival; thus, interest is high in identifying predictive and prognostic biomarkers and novel therapeutic agents. Although the costs of ovarian cancer care are likely to increase as newer, more effective, but more expensive treatment regimens become available, information on the current costs of care for ovarian cancer-across the care continuum from diagnosis to the end of life-are lacking. This study aimed to estimate real-world mean and median costs of ovarian cancer care within the first 5 years after diagnosis by patients' phase of care, age, race/ethnicity, and geographic region. We performed a retrospective cohort study of ovarian cancer patients diagnosed between January 1, 2015 and December 31, 2020. We used claims data from Optum's deidentified Clinformatics Data Mart database, which includes inpatient, outpatient, and prescription claims for commercial insurance and Medicare beneficiaries nationwide. Cost of ovarian cancer care were calculated for the start of care (ie, the first 6 months), continuing care (ie, period between the initial and end-of-life care), and end-of-life care (ie, the last 6 months) phases and reported in 2021 U.S. dollar amounts. Ovarian cancer care costs were stratified by age, race/ethnicity, and geographic region. Due to the skewed nature of cost data, the mean cost data were log-transformed for modeling. Ordinary least-squares regression was conducted on the log costs, adjusting for patient categorical age, race/ethnicity, and geographic region. A total of 7913 patients were included in the analysis. The mean cost per year for ovarian cancer care was >$200,000 during the start of care, between $26,000 and $88,000 during the continuing care phase, and >$129,000 during the end-of-life care phase. There were statistically significant associations between age and costs during each phase of care. Compared to younger patients, older patients incurred higher costs during the continuing care phase and lower costs during the end-of-life care phase. Geographic differences in the costs of ovarian cancer care were also noted regardless of the phase of care. There were no associations between cost and race/ethnicity in our cohort. Ovarian cancer care costs are substantial and vary by the phase of care, age category, and geographic region. As more effective but expensive treatment options for ovarian cancer become available with potential survival benefit, sustainable interventions to reduce the cost of care for ovarian cancer will be needed throughout the cancer care continuum.

Presence of atypical extravillous trophoblast foci is an independent predictor of the risk of progression to postmolar neoplasia

Amongst complete hydatidiform moles, 15% to 20% will progress to postmolar neoplasia. Scientists have long searched for routinely applicable prognostic markers that can efficiently predict the risk of postmolar neoplasia. To assess the prognostic value of atypical extravillous trophoblast foci within complete hydatidiform moles on the development of postmolar gestational trophoblastic neoplasia. Between January 2017 and December 2022, a retrospective multicenter study was conducted in the Belgian Gestational Trophoblastic Diseases Registry (French-speaking center). All complete hydatidiform moles were included after being confirmed by a systematic centralized pathological review in 3 academic units with a high exposure to placental pathology. Postmolar gestational trophoblastic neoplasia was diagnosed according to the International Federation of Gynecology and Obstetrics 2000 criteria. Atypical extravillous trophoblast foci were defined as trophoblastic clusters in the intervillous chamber with a biphasic pattern of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts. Their prognostic value for the development of postmolar gestational trophoblastic neoplasia was assessed using univariate analysis, followed by a multivariate model with stepwise selection of variables having a P value below .10 in the univariate analysis. A risk score, the "R-score," was developed based on the most significant variables of the multivariate model. The intercept and coefficients were obtained by fitting a logistic regression model. To facilitate its use in clinical practice, we established a score ranging from 0 to 10. Of the 216 patients with complete hydatidiform mole, 56 patients subsequently developed postmolar gestational trophoblastic neoplasia (25.9%). Atypical extravillous trophoblast foci were found in 105/216 cases (48.6%). The risk of postmolar neoplasia was significantly associated with the presence of this pathological feature in univariate analysis (odds ratio, 2.93, P=.0010) and in multivariate logistic regression adjusted for confounding variables (odds ratio, 2.34, P=.0152). The R-score is based on the presence of atypical extravillous trophoblast foci, age, and postevacuation human chorionic gonadotropin levels, with an area under the curve of 0.721. A score below 6 indicates a low risk of postmolar neoplasia (15%), while a score of 7 or higher indicates a high risk (42%). The presence of atypical extravillous trophoblast into complete moles is associated with the risk of developing postmolar gestational trophoblastic neoplasia. These foci may represent a new inexpensive and widely available histological prognostic marker.

A potential path toward standardized radical hysterectomy

Associations of obesity with post-treatment risks of cervical precancer and cancer

Individuals with obesity have an increased risk of cervical cancer, in part related to challenges associated with cervical sampling and visualization that result in missed detection of cervical precancers. The influence of obesity on the effectiveness of excisional treatment of detected cervical precancers and posttreatment disease risk is unknown. The aim of this study was to evaluate posttreatment risks of cervical precancer and cancer by body mass index (BMI). This retrospective cohort study included individuals aged 25 years and older undergoing excisional treatment for cervical precancer, either cervical intraepithelial neoplasia (CIN) grade 2 or 3 or adenocarcinoma in situ as of January 2017 with follow-up through February 2023. Patients were excluded if they were missing BMI, had cancer upon excision or had hysterectomy in lieu of excision, or were missing a valid referral screening visit. We categorized BMI as follows: underweight/normal (<25 kg/m Among 10,614 patients, a total of 680 (6.4%) developed post-treatment CIN3+; most (91%) within 2 years of treatment. Two-year CIN3+ and cancer risks were highest in those with obesity (8.65%, 95% CI, 7.6%-9.9% and 0.79%, 95% CI, 0.5%-1.2%, respectively) and lowest in those with normal weight (5.57%, 95% CI, 4.9%-6.3% and 0.29%, 95% CI, 0.2%-0.5%, respectively). Hazard ratios measuring associations of BMI with risk of posttreatment CIN3+ ranged from 1.19 (95% CI, 1.0-1.4) among those with overweight to 1.89 (95% CI, 1.4-2.6) among those with class III obesity (P-trend<.0001). A similar trend was observed for cancer, from 1.62 (95% CI, 0.8-3.3) for overweight and 3.50 (95% CI, 1.3-9.3) for class III obesity (P-trend=.016). Patients with obesity undergoing excisional treatment for cervical precancer have a higher risk of residual or recurrent disease, likely due to incomplete excision.

Patient-reported quality of life following prophylactic surgery for breast and ovarian cancer prevention: response

The impact of body mass index on the risk of postoperative complications following myomectomy

Uterine leiomyomas are common benign neoplasms, often causing symptoms like abnormal uterine bleeding, pelvic pain, and subfertility, with treatment options ranging from medical management to surgical interventions such as myomectomy. While myomectomy is effective in symptom relief, the impact of body mass index (BMI) on postoperative complications remains underexplored, warranting further investigation. This study aimed to assess the relationship between BMI and short-term postoperative complications after myomectomy. An analysis of major and minor 30-day postoperative complications stratified by BMI among patients who underwent abdominal or laparoscopic (conventional or robotic-assisted) myomectomy was conducted using data from the American College of Surgeons National Surgical Quality Improvement Program database from 2012 to 2020. Vaginal myomectomy cases were excluded from this study. Complications were stratified according to the Clavien-Dindo classification. A total of 27,387 cases were included. Postoperative complications occurred in 11.4% of cases (n=3131), ranging from 9.4% among patients who were underweight (n=26) to 16.1% among patients with obesity class 3 (n=350) (P<.001). In multiple regression analysis, patients with obesity class 1 experienced fewer major postoperative complications (adjusted odds ratio, 0.71; 95% confidence interval, 0.53-0.96) than those with normal BMI. Conversely, patients with obesity class 2 demonstrated more complications (adjusted odds ratio, 1.18; 95% confidence interval, 1.03-1.35), including minor complications (adjusted odds ratio, 1.17; 95% confidence interval, 1.02-1.34), than those with normal BMI. In addition, patients with obesity class 3 demonstrated more complications (adjusted odds ratio, 1.26; 95% confidence interval, 1.08-1.47), including minor (adjusted odds ratio, 1.21; 95% confidence interval, 1.03-1.42) and major (adjusted odds ratio, 1.41; 95% confidence interval, 1.01-21.99) complications, than those with normal BMI. Similar outcomes were observed when analyzing abdominal myomectomy exclusively, with disparities being much less pronounced when the analysis was confined to laparoscopic myomectomy. Patients with class 2 or 3 obesity are at increased odds of experiencing complications after myomectomy, whereas those with a slightly elevated body mass index may experience a protective effect. Complications related to BMI predominantly manifest after abdominal myomectomy procedures rather than after laparoscopic approaches.

Geographic and racial disparities in the quality of surgical care among patients with nonmetastatic uterine cancer

Although the rates of minimally invasive surgery and sentinel lymph node biopsy have increased considerably over time in the surgical management of early-stage uterine cancer, practice varies significantly in the United States, and there are disparities among low-volume centers and patients of Black race. A significant number of counties in the United States are without a gynecologic oncologist, and almost half of the counties with the highest gynecologic cancer rates lack a local gynecologic oncologist. This study aimed to evaluate the relationships of distance traveled and proximity to gynecologic oncologists with the receipt of and racial disparities in the quality of surgical care among patients who underwent a hysterectomy for nonmetastatic uterine cancer. Patients who underwent a hysterectomy for nonmetastatic uterine cancer in Kentucky, Maryland, Florida, and North Carolina were identified in the 2012 to 2018 State Inpatient Database and the State Ambulatory Surgery Services Database files. County-to-county distances were used as the distances traveled to the nearest gynecologic oncologist. Factors associated with the receipt of minimally invasive surgery and lymph node dissection were analyzed using multivariable logistic regression models, as was the assessment of the interaction between travel for surgery and patient race. Among 21,837 cases, 45.5% lived in a county without a gynecologic oncologist; overall, 55.5% traveled to another county for surgery, including 88% of those who lacked a local gynecologic oncologist. Patients who lacked access to a local gynecologic oncologist in their county who did not travel for surgery were more likely to receive open surgery and no lymph node dissection, and those in counties without access in any surrounding county were affected even more. Among patients in counties without a gynecologic oncologist, those who traveled for surgery had a similar likelihood of undergoing minimally invasive surgery (71%) but had a greater likelihood of undergoing lymph node dissection (64.7% vs 57.2%) than nontravelers. Among those in counties without a gynecologic oncologist, a longer distance traveled was associated with receipt of a lymph node assessment. When compared with non-Black patients, Black patients were less likely to undergo minimally invasive surgery (57.0% vs 74.1%). In adjusted regression models that controlled for a diagnosis of fibroids, Black race was an independent risk factor for the receipt of open surgery. There was a significant interaction between Black race and travel for surgery, and Black patients who lived in counties without a gynecologic oncologist who did not travel faced an incrementally lower likelihood of receiving minimally invasive surgery (odds ratio, 0.57 when compared with non-Black patients who traveled for surgery; odds ratio, 0.60 as interaction term; P<.001 for both). Similar disparities in surgical quality by race were noted for Black patients who lived in counties with a gynecologic oncologist who traveled out of county for surgery. Patients, particularly those of Black race, who lacked local access to gynecologic oncologist specialty care benefitted from traveling to specialty centers to ensure access to high-quality surgery for nonmetastatic uterine cancer. Further work is needed to ensure equitable and universal access to high-quality care through patient travel or specialist outreach.

Human papillomavirus genotypes and risk of persistence and progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2

In recent years, active surveillance has been introduced as an alternative to excisional treatment in younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment is associated with increased risk of preterm birth. However, early identification of women at increased risk of persistence/progression is important to ensure timely treatment. Evidence is limited on biomarkers that may be used to identify women at increased risk of persistence/progression. This study aimed to describe human papillomavirus HPV type-specific persistence/progression in women undergoing active surveillance for cervical intraepithelial neoplasia grade 2. We conducted a historical cohort study of women aged 23 to 40 years diagnosed with cervical intraepithelial neoplasia grade 2 at Aarhus University Hospital from 2000 to 2010. Women were identified through the Danish Pathology Data Bank (DPDB) and were considered as undergoing active surveillance if they had a first record of a cervical biopsy within 2 years after index diagnosis and no loop electrosurgical excision procedure before this. Human papillomavirus genotyping was performed on archived tissue samples using the HPV SPF A total of 455 women were included. Two-thirds were aged ≤30 years (73.8%) at index diagnosis, and nearly half had a high-grade index cytology (48.8%). Overall, 52.2% of all women had cervical intraepithelial neoplasia grade ≥2 during follow-up; 70.5% were human papillomavirus-16-positive and 29.5% were positive for other human papillomavirus types. Human papillomavirus-16 was associated with a significantly higher risk of persistence/progression (relative risk, 1.64; 95% confidence interval, 1.37-1.95) compared with non-human papillomavirus-16. The risk of persistence/progression was highest in human papillomavirus-16-positive women with a high-grade index cytology compared with human papillomavirus-16-positive women with a low-grade cytology (relative risk, 1.29; 95% confidence interval, 1.03-1.61), whereas no differences were observed across age groups. The highest risk of persistence/progression was observed among human papillomavirus-16-positive women, particularly those with associated high-grade cytology. These findings suggest that early excisional treatment should be considered in this group of women.

Quality of life after risk-reducing surgery for breast and ovarian cancer prevention: a systematic review and meta-analysis

This study aimed to assess the impact of risk-reducing surgery for breast cancer and ovarian cancer prevention on quality of life. We considered risk-reducing mastectomy, risk-reducing salpingo-oophorectomy, and risk-reducing early salpingectomy and delayed oophorectomy. We followed a prospective protocol (International Prospective Register of Systematic Reviews: CRD42022319782) and searched MEDLINE, Embase, PubMed, and Cochrane Library from inception to February 2023. We followed a PICOS (population, intervention, comparison, outcome, and study design) framework. The population included women at increased risk of breast cancer or ovarian cancer. We focused on studies reporting quality of life outcomes (health-related quality of life, sexual function, menopause symptoms, body image, cancer-related distress or worry, anxiety, or depression) after risk-reducing surgery, including risk-reducing mastectomy for breast cancer and risk-reducing salpingo-oophorectomy or risk-reducing early salpingectomy and delayed oophorectomy for ovarian cancer. We used the Methodological Index for Non-Randomized Studies (MINORS) for study appraisal. Qualitative synthesis and fixed-effects meta-analysis were performed. A total of 34 studies were included (risk-reducing mastectomy: 16 studies; risk-reducing salpingo-oophorectomy: 19 studies; risk-reducing early salpingectomy and delayed oophorectomy: 2 studies). Health-related quality of life was unchanged or improved in 13 of 15 studies after risk-reducing mastectomy (N=986) and 10 of 16 studies after risk-reducing salpingo-oophorectomy (N=1617), despite short-term deficits (N=96 after risk-reducing mastectomy and N=459 after risk-reducing salpingo-oophorectomy). Sexual function (using the Sexual Activity Questionnaire) was affected in 13 of 16 studies (N=1400) after risk-reducing salpingo-oophorectomy in terms of decreased sexual pleasure (-1.21 [-1.53 to -0.89]; N=3070) and increased sexual discomfort (1.12 [0.93-1.31]; N=1400). Hormone replacement therapy after premenopausal risk-reducing salpingo-oophorectomy was associated with an increase (1.16 [0.17-2.15]; N=291) in sexual pleasure and a decrease (-1.20 [-1.75 to -0.65]; N=157) in sexual discomfort. Sexual function was affected in 4 of 13 studies (N=147) after risk-reducing mastectomy, but stable in 9 of 13 studies (N=799). Body image was unaffected in 7 of 13 studies (N=605) after risk-reducing mastectomy, whereas 6 of 13 studies (N=391) reported worsening. Increased menopause symptoms were reported in 12 of 13 studies (N=1759) after risk-reducing salpingo-oophorectomy with a reduction (-1.96 [-2.81 to -1.10]; N=1745) in the Functional Assessment of Cancer Therapy - Endocrine Symptoms. Cancer-related distress was unchanged or decreased in 5 of 5 studies after risk-reducing mastectomy (N=365) and 8 of 10 studies after risk-reducing salpingo-oophorectomy (N=1223). Risk-reducing early salpingectomy and delayed oophorectomy (2 studies, N=413) led to better sexual function and menopause-specific quality of life. Risk-reducing surgery may be associated with quality of life outcomes. Risk-reducing mastectomy and risk-reducing salpingo-oophorectomy reduce cancer-related distress, and do not affect health-related quality of life. Women and clinicians should be aware of body image problems after risk-reducing mastectomy, and of sexual dysfunction and menopause symptoms after risk-reducing salpingo-oophorectomy. Risk-reducing early salpingectomy and delayed oophorectomy may be a promising alternative to mitigate quality of life-related risks of risk-reducing salpingo-oophorectomy.

Comparing the performance of 2 human papillomavirus assays for a new use indication: a real-world evidence-based evaluation in the United States

The US Food and Drug Administration supports innovations to facilitate new indications for high-risk human papillomavirus testing. This report describes the retrospective testing of stored specimens and analysis of existing data to efficiently and cost-effectively support a new indication for the Onclarity human papillomavirus assay (Becton, Dickinson and Company, BD Life Sciences - Integrated Diagnostic Solutions, Sparks, MD). The performance of this index test was compared with that of a predicate test, the cobas human papillomavirus assay (Roche Diagnostics, Indianapolis, IN). Both human papillomavirus assays are based on real-time polymerase chain reaction platforms that detect the presence of 14 high-risk human papillomavirus genotypes. The predicate assay reports human papillomavirus types 16 and 18 as individual results and the other 12 human papillomavirus genotypes as 1 pooled result. The index assay reports 9 independent results (human papillomavirus types 16, 18, 31, 33/58, 35/39/68, 45, 51, 52, and 56/59/66). Both the index and predicate assays are approved by the Food and Drug Administration for cervical cancer screening, but at the time that this study was initiated, the index human papillomavirus assay was not approved for use with cervical specimens collected in PreservCyt (Hologic, Inc, San Diego, CA) liquid-based cytology media. The performance of the index human papillomavirus assay was compared with that of the predicate human papillomavirus assay for the detection of cervical intraepithelial neoplasia grades 2 or greater and 3 or greater (≥CIN2 or ≥CIN3) using PreservCyt liquid-based cytology specimens collected from women aged 21 to 65 years. In addition, the ability of the index test's extended genotyping to stratify ≥CIN2 and ≥CIN3 risks, using these specimens, was evaluated. The New Mexico HPV Pap Registry was used to select an age- and cytology-stratified random sample of 19,879 women undergoing opportunistic cervical screening and follow-up in routine clinical practice across New Mexico. A subset (n = 4820) of PreservCyt specimens was selected from 19,879 women for paired testing by the index and predicate human papillomavirus assays within age and cytology strata and included women with or without cervical biopsy follow-up. Point estimate differences and ratios were calculated for cervical disease detection and positivity rates, respectively, with 95% confidence intervals to determine statistical significance. The cumulative risk of ≥CIN2 or ≥CIN3, with up to 5-year follow-up, was estimated for the index assay using Kaplan-Meier methods. The 5-year cumulative ≥CIN3 detection rates were 5.6% for the index assay and 4.6% for the predicate assay (difference, 1.0%; 95% confidence interval, 0.5%-1.5%). The ≥CIN3 positivity rates within <1 year were 95.3% for the index assay and 94.5% for the predicate assay (ratio, 1.01; 95% confidence interval, 0.98-1.06). The ≥CIN3 cumulative positivity rates for the index and predicate assays were also similar at 5 years. Among cases of ≥CIN3, the positive agreement rates between the index and predicate assays for human papillomavirus types 16 and 18 were 100.0% (95% confidence interval, 95.0%-100.0%) and 90.9% (95% confidence interval, 62.3%-98.4%), respectively. Human papillomavirus type 16 carried the highest ≥CIN2 or ≥CIN3 risk, followed by human papillomavirus types 18/31/33/58/52/45 and human papillomavirus types 35/56/59/51/56/59/66. The index and predicate human papillomavirus assays demonstrated equivalent performance, and extended human papillomavirus genotyping, using the index assay, provided effective ≥CIN2 and ≥CIN3 risk stratification, supporting a new indication for use of the index assay with PreservCyt.

Clinical course of cervical intraepithelial neoplasia grade 2: a population-based cohort study

Cervical intraepithelial neoplasia grade 2 has historically been the threshold for surgical excision, but because of high regression rates, many countries are transitioning to active surveillance. However, estimates for regression rates are based on small studies with heterogeneous definitions of regression and progression. This study aimed to describe regression and progression rates of cervical intraepithelial neoplasia grade 2 using nationwide healthcare registry data. This was a nationwide population-based cohort study on women aged 18 to 40 years who had undergone active surveillance for cervical intraepithelial neoplasia grade 2 in Denmark from 1998 to 2020. This study excluded women with a previous record of cervical intraepithelial neoplasia grade 2 or worse or surgical excision. Cumulative incidence functions were used to estimate the rates of regression and progression at 6, 12, 18, and 24 months after diagnosis. In addition, a modified Poisson regression was used to estimate the crude and adjusted relative risks of progression within 24 months stratified by index cytology and age. During the study period, 11,056 women underwent active surveillance, 6767 of whom regressed and 3580 of whom progressed within 24 months. This corresponded to regression rates of 62.9% (95% confidence interval, 61.9-63.8) and progression rates of 33.3% (95% confidence interval, 32.4-34.2) at 24 months of follow-up. Most women regressed (90%) or progressed (90%) within the first 12 months. Women with high-grade index cytology had a higher risk of progression than women with normal index cytology (adjusted relative, 1.58; 95% confidence interval, 1.43-1.76), whereas there was no difference in the risk of progression between women aged 30 and 40 years and women aged 23 to 29 years (adjusted relative risk, 0.98; 95% confidence interval, 0.88-1.10). The observed high regression rates of cervical intraepithelial neoplasia grade 2 supported the transition in clinical management from surgical excision to active surveillance, particularly among women with low-grade or normal index cytology.

Survival associated with extent of radical hysterectomy in early-stage cervical cancer: a subanalysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

International guidelines recommend tailoring the radicality of hysterectomy according to the known preoperative tumor characteristics in patients with early-stage cervical cancer. This study aimed to assess whether increased radicality had an effect on 5-year disease-free survival in patients with early-stage cervical cancer undergoing radical hysterectomy. The secondary aims were 5-year overall survival and pattern of recurrence. This was an international, multicenter, retrospective study from the Surveillance in Cervical CANcer (SCCAN) collaborative cohort. Patients with the International Federation of Gynecology and Obstetrics 2009 stage IB1 and IIA1 who underwent open type B/C1/C2 radical hysterectomy according to Querleu-Morrow classification between January 2007 and December 2016, who did not undergo neoadjuvant chemotherapy and who had negative lymph nodes and free surgical margins at final histology, were included. Descriptive statistics and survival analyses were performed. Patients were stratified according to pathologic tumor diameter. Propensity score match analysis was performed to balance baseline characteristics in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy. A total of 1257 patients were included. Of note, 883 patients (70.2%) underwent nerve-sparing radical hysterectomy, and 374 patients (29.8%) underwent non-nerve-sparing radical hysterectomy. Baseline differences between the study groups were found for tumor stage and diameter (higher use of non-nerve-sparing radical hysterectomy for tumors >2 cm or with vaginal involvement; P<.0001). The use of adjuvant therapy in patients undergoing nerve-sparing and non-nerve-sparing radical hysterectomy was 27.3% vs 28.6%, respectively (P=.63). Five-year disease-free survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 90.1% (95% confidence interval, 87.9-92.2) vs 93.8% (95% confidence interval, 91.1-96.5), respectively (P=.047). Non-nerve-sparing radical hysterectomy was independently associated with better disease-free survival at multivariable analysis performed on the entire cohort (hazard ratio, 0.50; 95% confidence interval, 0.31-0.81; P=.004). Furthermore, 5-year overall survival in patients undergoing nerve-sparing vs non-nerve-sparing radical hysterectomy was 95.7% (95% confidence interval, 94.1-97.2) vs non-nerve-sparing 96.5% (95% confidence interval, 94.3-98.7), respectively (P=.78). In patients with a tumor diameter ≤20 mm, 5-year disease-free survival was 94.7% in nerve-sparing radical hysterectomy vs 96.2% in non-nerve-sparing radical hysterectomy (P=.22). In patients with tumors between 21 and 40 mm, 5-year disease-free survival was 90.3% in non-nerve-sparing radical hysterectomy vs 83.1% in nerve-sparing radical hysterectomy (P=.016) (no significant difference in the rate of adjuvant treatment in this subgroup, P=.47). This was confirmed after propensity match score analysis (balancing the 2 study groups). The pattern of recurrence in the propensity-matched population did not demonstrate any difference (P=.70). For tumors ≤20 mm, no survival difference was found with more radical hysterectomy. For tumors between 21 and 40 mm, a more radical hysterectomy was associated with improved 5-year disease-free survival. No difference in the pattern of recurrence according to the extent of radicality was observed. Non-nerve-sparing radical hysterectomy was associated with better 5-year disease-free survival than nerve-sparing radical hysterectomy after propensity score match analysis.

Ovarian cancer incidence and death in average-risk women undergoing bilateral salpingo-oophorectomy at benign hysterectomy

Opportunistic bilateral salpingo-oophorectomy is often offered to patients undergoing benign hysterectomy to prevent ovarian cancer, but the magnitude of risk reduction obtained with bilateral salpingo-oophorectomy in this population remains unclear and must be weighed against potential risks of ovarian hormone deficiency. This study aimed to quantify the relative and absolute risk reduction in ovarian cancer incidence and death associated with bilateral salpingo-oophorectomy at the time of benign hysterectomy. We performed a population-based cohort study of all adult women (≥20 years) undergoing benign hysterectomy from 1996 to 2010 in Ontario, Canada. Patients with ovarian pathology, previous breast or gynecologic cancer, or evidence of genetic susceptibility to malignancy were excluded. Inverse probability of treatment-weighted Fine-Gray subdistribution hazard models were used to quantify the effect of bilateral salpingo-oophorectomy on ovarian cancer incidence and death while accounting for competing risks and adjusting for demographic characteristics, gynecologic conditions, and comorbidities. Analyses were performed in all women and specifically in women of postmenopausal age (≥50 years) at the time of hysterectomy. We identified 195,282 patients (bilateral salpingo-oophorectomy, 24%; ovarian conservation, 76%) with a median age of 45 years (interquartile range, 40-51 years). Over a median follow-up of 16 years (interquartile range, 12-20 years), 548 patients developed ovarian cancer (0.3%), and 16,170 patients (8.3%) died from any cause. Bilateral salpingo-oophorectomy was associated with decreased ovarian cancer incidence (hazard ratio, 0.23; 95% confidence interval, 0.14-0.38; P<.001) and decreased ovarian cancer death (hazard ratio, 0.30; 95% confidence interval, 0.16-0.57; P<.001). At 20 years follow-up, the weighted cumulative incidences of ovarian cancer were 0.08% and 0.46% with bilateral salpingo-oophorectomy and ovarian conservation, respectively, yielding an absolute risk reduction of 0.38% (95% confidence interval, 0.32-0.45; number needed to treat, 260). After restricting to women aged ≥50 years at hysterectomy, the absolute risk reduction was 0.62% (95% confidence interval, 0.47-0.77; number needed to treat, 161). Bilateral salpingo-oophorectomy resulted in a significant absolute reduction in ovarian cancer among women undergoing benign hysterectomy. Population-average risk estimates derived in this study should be balanced against other potential implications of bilateral salpingo-oophorectomy to inform practice guidelines, patient decision-making, and surgical management.

Examining indicators of early menopause following opportunistic salpingectomy: a cohort study from British Columbia, Canada

The fallopian tube may often be the site of origin for the most common and lethal form of ovarian cancer, high-grade serous ovarian cancer. As a result, many colleges of obstetrics and gynecology, which include the American College of Obstetricians and Gynecologists, are recommending surgical removal of the fallopian tube (bilateral salpingectomy) at the time of other gynecologic surgeries (particularly hysterectomy and tubal sterilization) in women at general population risk for ovarian cancer, collectively referred to as opportunistic salpingectomy. Previous research has illustrated no increased risk of complications after opportunistic salpingectomy. However, most studies that have examined potential hormonal consequences of opportunistic salpingectomy have had limited follow-up time and have focused on surrogate hormonal markers. We examine whether there are differences in physician visits for menopause and filling a prescription for hormone replacement therapy among women who undergo opportunistic salpingectomy in the population of British Columbia, Canada. We identified all women who were ≤50 years old in British Columbia who underwent opportunistic salpingectomy from 2008-2014. We compared women who underwent opportunistic salpingectomy at hysterectomy with women who underwent hysterectomy alone and women who underwent opportunistic salpingectomy for sterilization with women who underwent tubal ligation. We used Cox Proportional hazards models to model time to physician visits for menopause and for filling a prescription for hormone replacement therapy. We calculated adjusted hazards ratios for these outcomes and adjusted for other gynecologic conditions, surgical approach, and patient age. We performed an age-stratified analysis (<40, 40-44, 45-49 years) and conducted a sensitivity analysis that included only women with ≥5 years of follow up. We included 41,413 women in the study. There were 6861 women who underwent hysterectomy alone, 6500 who underwent hysterectomy with opportunistic salpingectomy, 4479 who underwent hysterectomy with bilateral salpingo-oophorectomy, 18,621 who underwent tubal ligation, and 4952 who underwent opportunistic salpingectomy for sterilization. In women who underwent opportunistic salpingectomy, there was no difference in time to the first physician visit related to menopause for both women who underwent hysterectomy with opportunistic salpingectomy (adjusted hazard ratio, 0.98; 95% confidence interval, 0.88-1.09) and women who underwent opportunistic salpingectomy for sterilization (adjusted hazard ratio, 0.92; 95% confidence interval, 0.77-1.10). There was also no difference in time to filling a prescription for hormone replacement therapy for women who underwent hysterectomy with opportunistic salpingectomy or opportunistic salpingectomy for sterilization (adjusted hazard ratio, 0.82; 95% confidence interval, 0.72-0.92; and adjusted hazard ratio, 1.00; 95% confidence interval, 0.89-1.12; respectively). In contrast, we report significantly increase hazards for time to physician visit for menopause (adjusted hazard ratio, 1.95; 95% confidence interval, 1.78, 2.13) and filling a prescription for hormone replacement therapy (adjusted hazard ratio, 3.80; 95% confidence interval, 3.45, 4.18) among women who underwent hysterectomy with bilateral salpingo-oophorectomy. There were no increased hazards for physician visits for menopause or initiation of hormone replacement therapy among women who underwent opportunistic salpingectomy in any of the age-stratified analyses, nor among women with at least 5 years of follow up. Our results reveal no indication of an earlier age of onset of menopause among the population of women who underwent hysterectomy with opportunistic salpingectomy and opportunistic salpingectomy for sterilization as measured by physician visits for menopause and initiation of hormone replacement therapy. Our findings are reassuring, given that earlier age at menopause is associated with increased mortality rates, particularly from cardiovascular disease.

Optimal follow-up strategy using high-risk human papillomavirus testing and cytology after conservative treatment for cervical adenocarcinoma in situ

After treatment for cervical adenocarcinoma in situ, patients remain a risk for recurrent adenocarcinoma in situ, cervical intraepithelial grade 3, or cervical cancer. This study aimed to determine the optimal follow-up strategy for high-risk human papillomavirus and cytology testing in conservatively treated patients with adenocarcinoma in situ. Patients were selected from a nationwide, retrospective cohort that included pathology reports from the Dutch Nationwide Pathology Databank (Palga) and survival data from the Central Bureau for Genealogy for patients conservatively treated for adenocarcinoma in situ between 1990 and 2021. The main outcome was the 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer stratified by single and consecutive human papillomavirus test and/or cytology results at 6, 12, 18, and 24 months. A total of 3411 patients were eligible for analysis. High-risk human papillomavirus test and/or cytology results in the first 5 years of follow-up were available in 3312 of 3411 patients (97.1%), including 5207 high-risk human papillomavirus test results of 1928 patients and 13,369 cytology results of 3306 patients. Up to 5 years after a single high-risk human papillomavirus test at 6 months after treatment, the incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer was lower among high-risk human papillomavirus-negative patients (2.3%; 95% confidence interval, 0.8-3.7) compared with high-risk human papillomavirus-positive patients (20.1%; 95% confidence interval, 14.2-25.5). Patients with normal cytology results 6 months after treatment for adenocarcinoma in situ had a lower incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer (3%; 95% confidence interval, 2.2-3.8) compared with patients with low-grade (5.9%; 95% confidence interval, 3.4-8.4) or high-grade cytology (52.1%; 95% confidence interval, 42.7-59.9). The 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer among patients testing negative for high-risk human papillomavirus consecutively at 6 and 12, 6 and 18, and 6 and 24 months was 0.6% (95% confidence interval, 0-1.8), 1.1% (95% confidence interval, 0-3.4), and 0% (95% confidence interval not applicable), respectively. Similarly, for patients with consecutive normal cotest results (high-risk human papillomavirus-negative with normal or low-grade cytology) at 6 and 12, 6 and 18, and 6 and 24 months, the 5-year cumulative incidence of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer was 0.6% (95% confidence interval, 0-1.8), 1.2% (95% confidence interval, 0-3.5), and 0% (95% confidence interval not applicable), respectively. After 2 consecutive negative high-risk human papillomavirus or normal cotests within 2 years after conservative adenocarcinoma in situ treatment, the risk of recurrent adenocarcinoma in situ, cervical intraepithelial neoplasia grade 3, or cervical cancer is low, and it seems acceptable to refer patients back to the national cervical cancer screening program, if applicable.

Colposcopic performance in a birth cohort previously eligible for human papillomavirus vaccination

Sweden started subsidized quadrivalent human papillomavirus vaccination for girls aged 13 to 17 in 2007. Since 2012, vaccination has been offered to all girls aged 10 to 12 within a school-based vaccination program, with a coverage of 80% or more. In addition, the vaccine has been offered on-demand as catch-up vaccination for girls aged 13 to 18, with a cumulative coverage of 55% to 60%. Since the first women in Sweden eligible for human papillomavirus vaccination entered the cervical screening program, questions on how to evaluate colposcopic findings among vaccinated women have arisen. Evidence is inconsistent on whether colposcopic features for the detection of cervical lesions are influenced by specific human papillomavirus genotypes and what role they can play in the prevention of invasive cervical cancer in vaccinated women. The primary objective of the study was to compare colposcopic evaluation in vaccinated and unvaccinated women entering the organized cervical screening program. Women in the 1994 and 1995 birth cohorts who entered the cervical screening program at age 23 in 1 region in Sweden were identified. Colposcopy was performed within 2 to 4 months after a positive screening result in accordance with national guidelines. Colposcopic performance was evaluated according to national guidelines with the Swede score and colposcopic impression. Punch biopsies were taken from colposcopic lesions and as "random biopsies" in the absence of lesions. These biopsies were used as the gold standard for the analysis. An endocervical sample was analyzed for cytologic findings and detection of 14 high-risk human papillomavirus genotypes. All colposcopic imaging was saved digitally for re-review. Vaccination status was obtained through linkage to national vaccination registries. Results were compared between vaccinated and unvaccinated women. In 2018 and 2019, 160 out of 165 (98%) women with a positive screening result attended colposcopy, of which 90 (56%) were vaccinated and 70 (44%) were unvaccinated. Only 7 out of 90 (5%) women in the vaccinated group were human papillomavirus 16/18-positive, compared with 23 out of 70 (33%) in the unvaccinated group (P<.001). There was a total of 61 out of 160 (38%) women with high-grade lesions-33 out of 90 (37%) in the vaccinated group and 28 out of 70 (40%) in the unvaccinated group (P=.697). There was 64% (21/33) of vaccinated women and 75% (21/28) of unvaccinated women with high-grade squamous intraepithelial lesions who had a Swede score of 6 to 10 (indicating high-grade squamous intraepithelial lesions) (P=.124). The sensitivity was slightly higher for the detection of high-grade squamous intraepithelial lesions in unvaccinated women using both colposcopic tests (Swede score, 0.67 vs 0.75; colposcopic impression, 0.67 vs 0.68), but the difference was not statistically significant. We found no statistically significant difference between the colposcopic evaluation of vaccinated and unvaccinated women, although human papillomavirus vaccination reduced the prevalence of human papillomavirus 16/18 infection in human papillomavirus-vaccinated women. Our results indicate that colposcopic examination is still a useful tool in vaccinated women entering the organized cervical screening program.

The impact of the COVID-19 pandemic on endometrial cancer and endometrial hyperplasia diagnoses: a population-based study

External validation of ultrasound-based models for differentiating between benign and malignant adnexal masses: a nationwide prospective multicenter study (IOTA phase 6)

The diagnostic performance of the IOTA methods, the O-RADS lexicon, and the RMI has been validated in prospective and retrospective studies, but most validation studies tested the performance in the hands of experienced ultrasound examiners. To prospectively validate the performance of the Risk of Malignancy Index, the International Ovarian Tumor Analysis Simple Rules Risk Model, the International Ovarian Tumor Analysis Assessment of Different NEoplasias in the adneXa model, and the International Ovarian Tumor Analysis 2-step strategy across different types of ultrasound centers in Italy. A retrospective post hoc analysis estimates malignancy prevalence in Ovarian-Adnexal Reporting and Data System risk groups when using the 2-step strategy or the Ovarian-Adnexal Reporting and Data System lexicon. This is a multicenter prospective observational study including regional referral centers and district hospitals in Italy. Consecutive patients with an adnexal mass examined with ultrasound by an International Ovarian Tumor Analysis-certified gynecologist with different levels of expertise were included, provided they underwent surgery <180 days after the inclusion scan. Ultrasound examination was performed transvaginally or transrectally and was supplemented with an abdominal scan when necessary. Reference standard was the histology of the adnexal mass following surgical removal. Discrimination (area under the receiver operating characteristic curve), calibration, and clinical utility were assessed to illustrate the diagnostic performance of the methods. For the retrospective post hoc analysis, we report the prevalence of malignancy in the Ovarian-Adnexal Reporting and Data System risk groups (Ovarian-Adnexal Reporting and Data System 2: risk of malignancy <1%; Ovarian-Adnexal Reporting and Data System 3: risk of malignancy 1% to <10%; Ovarian-Adnexal Reporting and Data System 4: risk of malignancy 10% to <50%; Ovarian-Adnexal Reporting and Data System 5: risk of malignancy ≥50%), with the Ovarian-Adnexal Reporting and Data System risk group assigned using either the 2-step strategy or the Ovarian-Adnexal Reporting and Data System lexicon. Between May 2017 and March 2020, 1431 patients were enrolled from 21 Italian centers (10 oncological and 11 nononcological). Based on histology, 995 (69.5%) tumors were benign and 436 (30.5%) were malignant (115, 8.0% borderline; 263, 18.4% primary invasive; 58, 4.1% metastatic tumors). For Risk of Malignancy Index, the area under the receiver operating characteristic curve was 0.85 (95% confidence interval, 0.81 to 0.87), whereas for all International Ovarian Tumor Analysis models (Simple Rules Risk Model, Assessment of Different NEoplasias in the adneXa with and without CA125, and 2-step strategy with and without CA125), the area under the receiver operating characteristic curves ranged from 0.91 (95% confidence interval, 0.88-0.93) to 0.92 (95% confidence interval, 0.89-0.94). All International Ovarian Tumor Analysis models demonstrated a higher net benefit than Risk of Malignancy Index across risk thresholds (exchange rates) from 1% to 50%. All International Ovarian Tumor Analysis models slightly underestimated the risk of malignancy, but Simple Rules Risk Model showed the least degree of underestimation. The prevalence of malignancy and the corresponding 95% confidence interval in the 4 Ovarian-Adnexal Reporting and Data System risk categories, as calculated using the 2-step strategy and Ovarian-Adnexal Reporting and Data System lexicon, were 0.97% (95% confidence interval, 0.4-2.6) and 1.2% (95% confidence interval, 0.5-2.9) for Ovarian-Adnexal Reporting and Data System 2, 7.2% (95% confidence interval, 5.0-10.3) and 6.0% (95% confidence interval, 3.6-9.6) for Ovarian-Adnexal Reporting and Data System 3, 37.9% (95% confidence interval, 32.4-43.8) and 27.8% (95% confidence interval, 23.6-32.5) for Ovarian-Adnexal Reporting and Data System 4, and 84% (95% confidence interval, 79.8-87.4) and 83.1% (95% confidence interval, 79.0-86.6) for Ovarian-Adnexal Reporting and Data System 5. Risk of Malignancy Index had lower ability than the International Ovarian Tumor Analysis models to distinguish between benign and malignant adnexal tumors in patients examined by either expert or nonexpert ultrasound operators in Italy. All the International Ovarian Tumor Analysis models-including Simple Rules Risk Model, Assessment of Different NEoplasias in the adneXa, and the 2-step strategy with or without CA125-had similar ability. The prevalence of malignancy in each of the 4 Ovarian-Adnexal Reporting and Data System risk categories closely matched the assigned malignancy risk regardless of whether the 2-step strategy or Ovarian-Adnexal Reporting and Data System lexicon was used.

Long-term lymphedema and quality of life following lymph node staging in early cervical cancer: 3-year follow-up in the prospective multicenter SENTIREC CERVIX study

Pelvic lymphadenectomy is the gold standard in nodal staging in cervical cancer but increases the risk of leg lymphedema. Sentinel lymph node mapping is a less invasive technique that enables accurate detection of nodal metastases, although evidence confirming its oncologic safety has yet to be established. Knowledge of chronic leg lymphedema and quality of life following pelvic lymphadenectomy or sentinel lymph node mapping is essential for informing treatment and survivorship strategies in women with cervical cancer, but current evidence is limited. This study aimed to evaluate long-term leg lymphedema after sentinel lymph node mapping alone and sentinel lymph node mapping with pelvic lymphadenectomy in women with cervical cancer, and to examine risk factors for leg lymphedema and condition-specific quality of life among patients with leg lymphedema at 12-month follow-up. This national prospective cohort study included patients with early-stage cervical cancer who underwent radical surgery, including sentinel lymph node mapping (2017-2021). In case of tumors >20 mm, backup pelvic lymphadenectomy was performed. Patients completed validated patient-reported outcome questionnaires before surgery and at 3, 12, 24, and 36 months postoperatively. Leg lymphedema was assessed using the European Organisation for Research and Treatment of Cancer cervix cancer module (QLQ-CX24), supplemented by 8 single items from the European Organisation for Research and Treatment of Cancer item library addressing lymphedema of the legs, genitals, and groin. Quality of life was reported according to the LYMQOL (Lymphoedema Quality of Life) tool and the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-CX24 modules. Mean difference scores from baseline to each follow-up were estimated with 95% confidence intervals, defining a change of ≥8 points as clinically important. Linear regression models were used to examine predictors of leg lymphedema 12 months postoperatively. We evaluated quality of life within LYMQOL domains in patients with lymphedema and analyzed domain trends using multiple linear regression. We compared quality of life between patients with and without leg lymphedema using guidelines for interpretation of clinically important differences. Among 109 women who underwent sentinel lymph node mapping alone, the leg lymphedema mean score differences from baseline to 3, 12, and 36 months were 6 (95% confidence interval, 2-10), 10 (95% confidence interval, 5-15), and 15 (95% confidence interval, 7-22), respectively. At similar time points, 77 women reported substantial leg lymphedema after sentinel lymph node mapping with pelvic lymphadenectomy, with mean score differences of 18 (95% confidence interval, 11-25), 29 (95% confidence interval, 21-37), and 21 (95% confidence interval, 11-32). Three-month leg lymphedema scores were positively associated with leg lymphedema scores at 12 months regardless of the extent of lymph node removal. Body mass index predicted leg lymphedema after sentinel lymph node mapping alone, whereas chemoradiotherapy was associated with lymphedema following backup pelvic lymphadenectomy. Reporting lymphedema at 12-month follow-up was associated with impairment in several quality of life aspects, including fatigue, pain, and physical, cognitive, social, and sexual functioning. Patients with cervical cancer reported long-term leg lymphedema, most pronounced after sentinel lymph node mapping with pelvic lymphadenectomy, and to a lesser extent after sentinel lymph node mapping alone. Three-month leg lymphedema score predicted persistent lymphedema, which was significantly associated with deterioration in several quality of life symptoms and functioning. Our findings support less invasive surgical approaches and may inform shared decision-making and survivorship intervention.

Uterine fibroids at single-cell resolution: unveiling cellular heterogeneity to improve understanding of pathogenesis and guide future therapies

Uterine leiomyomas or fibroids are benign tumors of the myometrium that affect approximately 70% of reproductive-age women. Fibroids continue to be the leading cause of hysterectomy, resulting in substantial healthcare costs. Genetic complexity and lack of cellular and molecular understanding of fibroids have posed considerable challenges to developing noninvasive treatment options. Over the years, research efforts have intensified to unravel the genetic and cellular diversities within fibroids to deepen our understanding of their origins and progression. Studies using immunostaining and flow cytometry have revealed cellular heterogeneity within these tumors. A correlation has been observed between genetic mutations in fibroids and their size, which is influenced by cellular composition, proliferation rates, and extracellular matrix accumulation. Fibroids with mediator complex subunit 12 (MED12) mutation are composed of smooth muscle cells and fibroblasts equally. In contrast, the fibroids with high-mobility group AT-hook 2 (HMGA2) translocation are 90% composed of smooth muscle cells. More recently, single-cell RNA sequencing in the myometrium and MED12 mutation carrying fibroids has identified further heterogeneity in smooth muscle cells and fibroblast cells, identifying 3 different smooth muscle cell populations and fibroblast cell populations. Although both myometrium and fibroids have similar cellular composition, these cells differs in their transcriptomic profile and have specialized roles, underscoring the complex cellular landscape contributing to fibroid pathogenesis. Furthermore, not all smooth muscle cells in MED12-mutant fibroid carry the MED12 mutation, suggesting that MED12-mutant fibroids might not be monoclonal in nature. This review describes the intricacies of fibroid biology revealed by single-cell RNA sequencing. These advances have identified new cellular targets for potential therapies, provided insights into treatment resistance, and laid the groundwork for more personalized approaches to fibroid management. As we continue to unravel the cellular and molecular complexity of fibroids, we anticipate that this knowledge will translate into more effective and less invasive treatments, ultimately improving outcomes for the millions of women affected by this condition.

Pelvic inflammatory disease and risk of epithelial ovarian cancer: a national population-based case-control study in Sweden

Epithelial ovarian cancer is an insidious disease, and women are often diagnosed when the disease is beyond curative treatment. Accordingly, identifying modifiable risk factors is of paramount importance. Inflammation predisposes an individual to cancer in various organs, but whether pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer has not been fully determined. This study aimed to investigate a possible association between clinically verified pelvic inflammatory disease and the risk of epithelial ovarian cancer. In this national population-based case-control study, all women in Sweden diagnosed with epithelial ovarian cancer between 1999 and 2020 and 10 controls for each were identified, matched for age and residential district. Using several Swedish nationwide registers, data on previous pelvic inflammatory disease and potential confounding factors (age, parity, educational level, and previous gynecologic surgery) were retrieved. Adjusted odds ratios and 95% confidence intervals were estimated using conditional logistic regression. Histotype-specific analyses were performed for the subgroup of women diagnosed with epithelial ovarian cancer between 2015 and 2020. Moreover, hormonal contraceptives and menopausal hormone therapy were adjusted in addition to the aforementioned confounders. This study included 15,072 women with epithelial ovarian cancer and 141,322 controls. Most women (9102 [60.4%]) had serous carcinoma. In a subgroup of cases diagnosed between 2015 and 2020, high-grade serous carcinoma (2319 [60.0%]) was identified. A total of 168 cases (1.1%) and 1270 controls (0.9%) were diagnosed with pelvic inflammatory disease. Previous pelvic inflammatory disease was associated with an increased risk of epithelial ovarian cancer (adjusted odds ratio, 1.39; 95% confidence interval, 1.17-1.66) and serous carcinoma (adjusted odds ratio, 1.46; 95% confidence interval, 1.18-1.80) for the entire study population. For the subgroup of women diagnosed in 2015-2020, pelvic inflammatory disease was associated with high-grade serous carcinoma (adjusted odds ratio, 1.43; 95% confidence interval, 1.01-2.04). The odds ratios of the other histotypes were as follows: endometrioid (adjusted odds ratio, 0.13; 95% confidence interval, 0.02-1.06), mucinous (adjusted odds ratio, 1.55; 95% confidence interval, 0.56-4.29), and clear cell carcinoma (adjusted odds ratio, 2.30; 95% confidence interval, 0.90-5.86). A dose-response relationship was observed between the number of pelvic inflammatory disease episodes and the risk of epithelial ovarian cancer (P A history of pelvic inflammatory disease is associated with an increased risk of epithelial ovarian cancer and a dose-response relationship is evident. Histotype-specific analyses show an association with increased risk of serous epithelial ovarian cancer and high-grade serous carcinoma and potentially also with clear cell carcinoma, but there is no significant association with other histotypes. Infection and inflammation of the upper reproductive tract might have serious long-term consequences, including epithelial ovarian cancer.

Risk of progression of cervical intraepithelial neoplasia grade 2 in human papillomavirus–vaccinated and unvaccinated women: a population-based cohort study

Many countries have implemented active surveillance (ie, leaving the lesion untreated) as an option among younger women with cervical intraepithelial neoplasia grade 2 because regression rates are high and excisional treatment increases the risk for preterm birth in subsequent pregnancies. However, early identification of women at increased risk for progression to cervical intraepithelial neoplasia grade 3 or worse is important to ensure timely treatment. Because women who have received a human papillomavirus vaccine have a lower risk for cervical cancer, they may have a lower risk for progression of untreated cervical intraepithelial neoplasia grade 2 to cervical intraepithelial neoplasia grade 3 or worse. This study aimed to investigate if women who received a human papillomavirus vaccine and who are undergoing active surveillance for cervical intraepithelial neoplasia grade 2 are less likely to progress to cervical intraepithelial neoplasia grade 3 or worse when compared with women who did not receive the vaccine. We conducted a population-based cohort study in Denmark using data from national health registers. We identified all women aged 18 to 40 years who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 from January 1, 2007, to December 31, 2020. Women with a previous record of cervical intraepithelial neoplasia grade 2 or worse, hysterectomy, or a loop electrosurgical excision procedure were excluded. Exposure was defined as having received ≥1 dose of a human papillomavirus vaccine at least 1 year before the cervical intraepithelial neoplasia grade 2 diagnosis. We used cumulative incidence functions to estimate the risk for progression to cervical intraepithelial neoplasia grade 3 or worse within 28 months using hysterectomy, emigration, and death as competing events. We used modified Poisson regression to calculate crude and adjusted relative risks of progression during the 28-month surveillance period. Results were stratified by age at vaccination and adjusted for index cytology, disposable income, and educational level. The study population consisted of 7904 women of whom 3867 (48.9%) were vaccinated at least 1 year before a diagnosis of cervical intraepithelial neoplasia grade 2. At the time of cervical intraepithelial neoplasia grade 2 diagnosis, women who were vaccinated were younger (median age, 25 years; interquartile range, 23-27 years) than those who were not (median age, 29 years; interquartile range, 25-33 years). The 28-month cumulative risk for cervical intraepithelial neoplasia grade 3 or worse was significantly lower among women who were vaccinated before the age of 15 years (22.9%; 95% confidence interval, 19.8-26.1) and between the ages of 15 and 20 years (31.5%; 95% confidence interval, 28.8-34.3) when compared with women who were not vaccinated (37.6%; 95% confidence interval, 36.1-39.1). Thus, when compared with women who were not vaccinated, those who were vaccinated before the age of 15 years had a 35% lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse (adjusted relative risk, 0.65; 95% confidence interval, 0.57-0.75), whereas women who were vaccinated between the ages of 15 and 20 years had a 14% lower risk (adjusted relative risk, 0.86; 95% confidence interval, 0.79-0.95). For women who were vaccinated after the age of 20 years, the risk was comparable with that among women who were not vaccinated (adjusted relative risk, 1.02; 95% confidence interval, 0.96-1.09). Women who were vaccinated and who were undergoing active surveillance for cervical intraepithelial neoplasia grade 2 had a lower risk for progression to cervical intraepithelial neoplasia grade 3 or worse during 28 months of follow-up when compared with women who were not vaccinated but only if the vaccine was administered by the age of 20 years. These findings may suggest that the human papillomavirus vaccination status can be used for risk stratification in clinical management of cervical intraepithelial neoplasia grade 2.

Implementation of human papillomavirus video education for women participating in mass cervical cancer screening in Tanzania

Because the global disease burden of cervical cancer is greatest in Africa, the World Health Organization has endorsed visual inspection with acetic acid screening with cryotherapy triage for the screen-and-treat approach. With the lowest doctor-to-patient ratio worldwide (1:50,000), Tanzania has nearly 10,000 new cases of cervical cancer and 7000 deaths annually. We report on the feasibility of visual inspection with acetic acid in the severely resource-limited Mwanza district and on the impact of intervening education on baseline human papillomavirus and cervical cancer knowledge. Two 5-day free visual inspection with acetic acid (VIA) clinics in urban Buzuruga and rural Sangabuye on the shores of Lake Victoria were approved by our university institutional review board and local Tanzanian health authorities. Participants completed a demographic survey and a 6-question (1 point per question) multiple choice test written in Kiswahili to assess baseline knowledge. A 15-minute educational video in Kiswahili (MedicalAidFilms: Understanding screening, treatment, and prevention of cervical cancer) was followed by repeated assessment using the same test, visual inspection with acetic acid screening, and optional HIV testing. Pre- and postvideo scores and change of score were analyzed via t test, analysis of variance, and multivariate regression. Significance was considered at P<.05. From July 2, 2018 to July 6, 2018, 825 women were screened, and 207 women (25.1%) were VIA positive (VIA+). One hundred forty-seven VIA+ nonpregnant women received same-day cryotherapy. Seven hundred sixty women participated in an educational intervention-61.6% of whom were from an urban site and 38.2% from a rural site. The mean age was 36.4 (standard deviation, 11.1). Primary languages were Kiswahili (62.2%) and Kisukuma (30.6%). Literacy was approximately 73%, and average education level was equivalent to the seventh grade (United States). Less than 20% of urban and rural women reported access to healthcare providers. Mean score of the participants before watching the video was 2.22 (standard deviation, 1.76) and was not different between VIA+ and VIA negative groups. Mean score of the participants after watching the video was 3.86 (standard deviation, 1.78). Postvideo scores significantly improved regardless of age group, clinic site, primary language, education level, literacy, or access to healthcare provider (P<.0001). Change of score after watching the video was significantly greater in participants from urban areas (1.99±2.07) than in those from rural areas (1.07±1.95) (P<.0001). Multivariate analysis identified urban site as an independent factor in change of score (P=.0211). Visual inspection with acetic acid screening for cervical cancer is feasible and accepted in northern Tanzania. Short video-based educational intervention improved baseline knowledge on the consequences of human papillomavirus infection in the studied populations. The impact was greater in the urban setting than in the rural setting.

Role of neighborhood context in ovarian cancer survival disparities: current research and future directions

Ovarian cancer is the fifth leading cause of cancer-associated mortality among US women with survival disparities seen across race, ethnicity, and socioeconomic status, even after accounting for histology, stage, treatment, and other clinical factors. Neighborhood context can play an important role in ovarian cancer survival, and, to the extent to which minority racial and ethnic groups and populations of lower socioeconomic status are more likely to be segregated into neighborhoods with lower quality social, built, and physical environment, these contextual factors may be a critical component of ovarian cancer survival disparities. Understanding factors associated with ovarian cancer outcome disparities will allow clinicians to identify patients at risk for worse outcomes and point to measures, such as social support programs or transportation aid, that can help to ameliorate such disparities. However, research on the impact of neighborhood contextual factors in ovarian cancer survival and in disparities in ovarian cancer survival is limited. This commentary focuses on the following neighborhood contextual domains: structural and institutional context, social context, physical context represented by environmental exposures, built environment, rurality, and healthcare access. The research conducted to date is presented and clinical implications and recommendations for future interventions and studies to address disparities in ovarian cancer outcomes are proposed.

FcγR3A polymorphism influences natural killer cell activation and response to anti-PD-L1 (avelumab) in gestational trophoblastic neoplasia

Low-risk gestational trophoblastic neoplasia are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line monochemotherapy or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity mediated by FcγR3A-expressing natural killer cells. This translational study aimed at testing whether antibody-dependent cell-mediated cytotoxicity is involved in avelumab efficacy on gestational trophoblastic neoplasia and if FcγR3A affinity polymorphism could help predicting the response to avelumab in gestational trophoblastic neoplasia. The expression of PD-L1 by the tumor and the phenotype of natural killer cells infiltrating gestational trophoblastic neoplasia were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human natural killer cells in the presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of natural killer cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were re-analyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab. We confirmed that FcγR3A+ natural killer cells infiltrated PD-L1-expressing gestational trophoblastic neoplasia. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced natural killer cell activation, which promoted the destruction of JEG-3 cells. Natural killer cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of antibody-dependent cell-mediated cytotoxicity, we demonstrated that high-affinity FcγR3A polymorphism on natural killer cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high-affinity FcγR3A polymorphism had better clinical response to avelumab. Our work demonstrates that antibody-dependent cell-mediated cytotoxicity contributes to the therapeutic effect of avelumab in gestational trophoblastic neoplasia and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant gestational trophoblastic neoplasia who are most likely to respond to avelumab.

Patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer

Sentinel lymph node mapping is a minimally invasive surgical staging procedure that allows identification of macro- and micrometastases. The implementation of sentinel lymph node mapping to women with low-grade endometrial cancer allows detection of lymph node metastases and avoids the morbidity of radical pelvic lymphadenectomy. The extent of myometrial invasion is highly predictive of lymph node metastases but is hard to determine precisely preoperatively. The exact rate of lymph node metastases in the large group of women with <50% myometrial invasion is low but unknown. The benefit of detecting metastases in this group should balance the risk of lymphedema. There is limited knowledge of early and late lymphedema and its impact on the quality of life in women with low-grade endometrial cancer following sentinel lymph node mapping. The primary objective was to investigate the risk of patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer. In addition, we aimed to evaluate risk factors for lymphedema and the condition-specific quality of life (QoL) among women who reported lymphedema 12 months after surgery. Women with presumed stage I low-grade endometrial cancer were included in a national prospective cohort study on sentinel lymph node mapping from March 2017 to February 2022. Women completed a package of validated patient-reported outcome measures before surgery, 3 and 12 months after surgery. The primary outcome was the leg lymphedema domain score from the European Organisation for Research and Treatment of Cancer-Endometrial Cancer Module (EORTC QLQ-EN24). The lymphedema assessment was further supplemented by 7 validated single items from the European Organisation for Research and Treatment of Cancer item library addressing lymphedema of legs, genitals, and groin. The disease-specific quality of life was assessed using the validated Lymphedema Quality of Life Tool. Scores were linearly transformed to 0 to 100. A change from baseline of 8 points in leg lymphedema sum-score was considered clinically important. Mean difference scores over time with 95% confidence interval were estimated. Multiple linear regression models evaluated baseline predictors associated with the 12 months postoperative lymphedema score, and if early lymphedema predicted lymphedema at 12 months after surgery. Lymphedema condition-specific quality of life was evaluated for women with lymphedema. Seventy-nine % (486/617) completed patient-reported outcome measures at baseline and 12 months. The mean difference score of leg lymphedema from baseline to 12 months was 5.0, confidence interval [3.3, 6.8], that is, below the threshold for clinical importance. Baseline leg lymphedema score and body mass index were positively associated with the leg lymphedema score at 12 months. The leg lymphedema score at 3 months was associated with a higher 12-month score. High scores of lymphedema at 12 months were negatively associated with the women's daily activities, appearance, emotional functioning, and global quality of life and increased their subjective symptom burden. Women with low-grade endometrial cancer have a low risk of lymphedema after sentinel lymph node mapping. Leg swelling at baseline and body mass index predicted more lymphedema at 12 months after surgery. Early lymphedema at 3 months predicted persistent lymphedema. A high leg lymphedema score at 12 months is associated with impairment in several aspects of quality of life.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden

The levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. We aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. A total of 514,719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1,544,157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. The use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99), and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P<.002), and 1.63 additional cases per 10,000 person-years. The risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It is important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

A low-cost approach to salpingectomy at cesarean delivery

There is increasing adoption of opportunistic salpingectomy for ovarian cancer prevention at the time of gynecologic surgery, which includes the postpartum period. However, there is no consensus on an ideal surgical approach for the parturient vasculature. We describe a safe, low-cost, and accessible approach for bilateral salpingectomy during cesarean delivery that we call the "Mesosalpinx Isolation Salpingectomy Technique" (MIST) that can guide institutions to standardize their postpartum salpingectomy procedures when advanced vessel-sealing devices are not available. In the MIST technique, avascular windows are created within the mesosalpinx close to the tubal vessels. The vasculature is thus fully skeletonized and isolated from the adjacent mesosalpinx before suture ligation, which ensures security of the free-tie to the individual vessels and avoids sharp injury to the mesosalpinx. Not using vessel-sealing devices also eliminates the risk of thermal injury to the adjacent ovarian tissue and vasculature and potentially achieves a cost-savings for the hospital and patient. MIST has been performed in 141 cesarean deliveries in the past 4 years. There were no noted bleeding complications during the salpingectomy procedure, blood transfusions, or instances of postoperative surgical reexploration. In our experience, a surgeon who is new to the procedure takes approximately 15 minutes to complete a bilateral salpingectomy. Those surgeons who are experienced in MIST need only 5 minutes. A video is included that demonstrates the technique.

Trends and clinical predictors in ovarian preservation in patients with low-risk endometrial cancer

For premenopausal patients with early-stage endometrial cancer, iatrogenic menopause raises concerns regarding cardiovascular risk, cognitive decline, and loss of future fertility. Although previous studies have demonstrated the safety of ovarian preservation in selected patients with low-risk endometrial cancer, and national guidelines support its use in selected cases, contemporary ovarian preservation practices and potential sociodemographic disparities in care delivery remain poorly characterized. This study aimed to assess national trends in ovarian preservation and identify clinical and sociodemographic factors associated with ovarian preservation among premenopausal women. We conducted a retrospective cohort study using the National Cancer Database, including women aged less than 45 years diagnosed with stage IA, grade 1 or 2 endometrioid endometrial cancer between January 1, 2004 and December 31, 2021. A subanalysis was performed among patients who also underwent lymph node assessment as proxy for patients with preoperative oncologic planning. Time trends were evaluated using the Cochran-Armitage trend test, and average annual percent change was estimated using a Poisson model. Group differences were assessed using Chi-squared or Fisher's exact tests, and logistic regression was used to evaluate associations between ovarian preservation and clinical and sociodemographic variables. A total of 4343 women met the inclusion criteria. Between 2004 and 2021, ovarian preservation rates declined from 16.7% to 3.7% (average annual percent change, -8.6%; 95% confidence interval, -10.4% to 6.6%; P<.0001). On multivariable logistic regression analysis, older age (odds ratio, 0.94; 95% confidence interval, 0.92-0.96; P<.001), grade 2 disease (odds ratio, 0.47; 95% confidence interval, 0.34-0.63; P<.0001), and treatment at academic/research facilities (odds ratio, 0.74; 95% confidence interval, 0.60-0.91; P=.006) were associated with lower odds of ovarian preservation. Race/ethnicity, insurance status, income, urban/rural residence, and distance to the diagnosing facility were not significantly associated with ovarian preservation. Among patients who underwent lymph node assessment, ovarian preservation similarly declined, from 5.6% in 2004 to 2.8% in 2021 (average annual percent change, -4.8%; 95% confidence interval, -8.9% to 0.62%; P=.03). In this cohort, older age at diagnosis (odds ratio, 0.92; 95% confidence interval, 0.89-0.96; P<.001) was associated with decreased odds of ovarian preservation and Asian/American Indian race/ethnicity (odds ratio, 3.43; 95% confidence interval, 1.97-6.04; P<.001) were associated with higher odds of ovarian preservation. Ovarian preservation remains underused in premenopausal patients with low-risk endometrial cancer despite guideline support and evidence highlighting its long-term health benefits. Older age, higher tumor grade, and treatment at academic centers influence practice, highlighting missed opportunities for evidence-based, patient-centered care. Further research is needed to better understand the drivers of these patterns and support more consistent, individualized surgical decision-making.

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness

Sentinel lymph node biopsy in high-grade endometrial cancer

Serum HE4 and diagnosis of ovarian cancer in postmenopausal women with adnexal masses

Transvaginal ultrasound and serum CA125 are routinely used for differential diagnosis of pelvic adnexal mass. Use of human epididymis 4 was approved in the United States in 2011. However, there is scarcity of studies evaluating the additional value of human epididymis 4. The objective of the study was to evaluate the performance characteristics of transvaginal ultrasound, CA125, and human epididymis 4 for differential diagnosis of ovarian cancer in postmenopausal women with adnexal masses. This was a cohort study nested within the screen arms of the multicenter randomized controlled trial, United Kingdom Collaborative Trial of Ovarian Cancer Screening, based in England, Wales, and Northern Ireland. In United Kingdom Collaborative Trial of Ovarian Cancer Screening, 48,230 women randomized to transvaginal ultrasound screening and 50,078 to multimodal screening (serum CA125 interpreted by Risk of Ovarian Cancer Algorithm with second line transvaginal ultrasound) underwent the first (prevalence) screen. Women with adnexal lesions and/or persistently elevated risk were clinically assessed and underwent surgery or follow-up for a median of 10.9 years. Banked samples taken within 6 months of transvaginal ultrasound from all clinically assessed women were assayed for human epididymis 4 and CA125. Area under the curve and sensitivity for diagnosing ovarian cancer of multiple penalized logistic regression models incorporating logCA125, log human epididymis 4, age, and simple ultrasound features of the adnexal mass were compared. Of 1590 (158 multimodal, 1432 ultrasound) women with adnexal masses, 78 were diagnosed with ovarian cancer (48 invasive epithelial ovarian, 14 type I, 34 type II; 24 borderline epithelial; 6 nonepithelial) within 1 year of scan. The area under the curve (0.893 vs 0.896; P = .453) and sensitivity (74.4% vs 75.6% ;P = .564) at fixed specificity of 90% of the model incorporating age, ultrasound, and CA125 were similar to that also including human epididymis 4. Both models had high sensitivity for invasive epithelial ovarian (89.6%) and type II (>91%) cancers. Our population cohort study suggests that human epididymis 4 adds little value to concurrent use of CA125 and transvaginal ultrasound in the differential diagnosis of adnexal masses in postmenopausal women.

Practice patterns and complications of hysterectomy for invasive cervical cancer after the Laparoscopic Approach to Cervical Cancer trial

After the publication of the Laparoscopic Approach to Cervical Cancer trial, the standard surgical approach for early-stage cervical cancer is open radical hysterectomy. Only limited data were available regarding whether the change to open abdominal hysterectomy observed after the Laparoscopic Approach to Cervical Cancer trial led to an increase in postoperative complication rates as a consequence of the decrease in the use of the minimally invasive approach. This study aimed to analyze whether there was a correlation between the publication of the Laparoscopic Approach to Cervical Cancer trial and an increase in the 30-day complications associated with surgical treatment of invasive cervical cancer. Data from the American College of Surgeons National Surgical Quality Improvement Program were used to compare the results in the pre-Laparoscopic Approach to Cervical Cancer period (January 2016 to December 2017) vs the results in the post-Laparoscopic Approach to Cervical Cancer period (January 2019 to December 2020). The rates of each surgical approach (open abdominal or minimally invasive) hysterectomy for invasive cervical cancer during the 2 periods were assessed. Subsequently, 30-day major complication, minor complication, unplanned hospital readmission, and intra- or postoperative transfusion rates before and after the publication of the Laparoscopic Approach to Cervical Cancer trial were compared. Overall, 3024 patients undergoing either open abdominal hysterectomy or minimally invasive hysterectomy for invasive cervical cancer were included in the study. Of the patients, 1515 (50.1%) were treated in the pre-Laparoscopic Approach to Cervical Cancer period, and 1509 (49.9%) were treated in the post-Laparoscopic Approach to Cervical Cancer period. The rate of minimally invasive approaches decreased significantly from 75.6% (1145/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 41.1% (620/1509) in the post-Laparoscopic Approach to Cervical Cancer period, whereas the rate of open abdominal approach increased from 24.4% (370/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 58.9% (889/1509) in the post-Laparoscopic Approach to Cervical Cancer period (P<.001). The overall 30-day major complications remained stable between the pre-Laparoscopic Approach to Cervical Cancer period (85/1515 [5.6%]) and the post-Laparoscopic Approach to Cervical Cancer period (74/1509 [4.9%]) (adjusted odds ratio, 0.85; 95% confidence interval, 0.61-1.17). The overall 30-day minor complications were similar in the pre-Laparoscopic Approach to Cervical Cancer period (103/1515 [6.8%]) vs the post-Laparoscopic Approach to Cervical Cancer period (120/1509 [8.0%]) (adjusted odds ratio, 1.17; 95% confidence interval, 0.89-1.55). The unplanned hospital readmission rate remained stable during the pre-Laparoscopic Approach to Cervical Cancer period (7.9% per 30 person-days) and during the post-Laparoscopic Approach to Cervical Cancer period (6.3% per 30 person-days) (adjusted hazard ratio, 0.78; 95% confidence interval, 0.58-1.04)]. The intra- and postoperative transfusion rates increased significantly from 3.8% (58/1515) in the pre-Laparoscopic Approach to Cervical Cancer period to 6.7% (101/1509) in the post-Laparoscopic Approach to Cervical Cancer period (adjusted odds ratio, 1.79; 95% confidence interval, 1.27-2.53). This study observed a significant shift in the surgical approach for invasive cervical cancer after the publication of the Laparoscopic Approach to Cervical Cancer trial, with a reduction in the minimally invasive abdominal approach and an increase in the open abdominal approach. The change in surgical approach was not associated with an increase in the rate of 30-day major or minor complications and unplanned hospital readmission, although it was associated with an increase in the transfusion rate.

Chemotherapy directly followed by poly(ADP-ribose) polymerase inhibition as an alternative to surgery in patients with BRCA-mutated ovarian cancer: a potential management strategy in the era of coronavirus disease 2019

Decidualized ovarian endometrioma

Reply: Further discussion and clarification of female vulvar anatomy

Ovarian cancer prognosis in women with endometriosis: a retrospective nationwide cohort study of 32,419 women

Contradicting results regarding ovarian cancer prognosis in women with endometriosis have been reported in the literature. Owing to the small sample size of previous studies, larger studies are required to elucidate the role of endometriosis in ovarian cancer prognosis. This study aimed to evaluate the survival rate in women with ovarian cancer with or without histologically proven endometriosis in a Dutch population-based cohort. All women with ovarian cancer diagnosed between 1990 and 2015 were identified from the Netherlands Cancer Registry. We linked these women with the Dutch nationwide registry of histopathology and cytopathology (Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief) to identify all women with histologically proven endometriosis. We compared the prognosis of patients with ovarian cancer with and without histologically proven endometriosis. Primary outcome was the overall survival with subgroup analyses stratified by histologic ovarian cancer subtype and stage. Multivariable Cox proportional hazard analysis was used to estimate hazard ratios with 95% confidence intervals. We included 32,419 patients with ovarian cancer, of whom 1979 (6.1%) had histologically proven endometriosis. The median age of histologic endometriosis diagnosis was 53 years (interquartile range, 46-62). Of all women with ovarian cancer and endometriosis, 81.2% received a diagnosis of synchronous endometriosis and ovarian cancer. The endometriosis cohort was younger at ovarian cancer diagnosis, had more favorable tumor characteristics, and more often had surgical treatment for ovarian cancer than the women without endometriosis. These variables were included in the multivariable model as confounders. Women with histologically proven endometriosis had a significantly better prognosis in both crude and adjusted analyses (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P<.0005, and adjusted hazard ratio, 0.89; 95% confidence interval, 0.83-0.95; P<.05, respectively). Women with ovarian cancer and histologically proven endometriosis had longer overall survival than women with ovarian cancer without endometriosis, even after adjustment for confounders. Future studies on ovarian cancer treatment and prognosis should consider stratifying by endometriosis status to elucidate its role. Furthermore, women diagnosed as having ovarian cancer and concurrent endometriosis should be explained the role of endometriosis in ovarian cancer survival.

Impact of Medicaid expansion on women with gynecologic cancer: a difference-in-difference analysis

Women with gynecologic cancer face socioeconomic disparities in care that affect survival outcomes. The Affordable Care Act offered states the option to expand Medicaid enrollment eligibility criteria as a means of improving timely and affordable access to care for the most vulnerable. The variable uptake of expansion by states created a natural experiment, allowing for quasi-experimental methods that offer more unbiased estimates of treatment effects from retrospective data than the traditional regression adjustment. To use a quasi-experimental, difference-in-difference framework to create unbiased estimates of impact of Medicaid expansion on women with gynecologic cancer. We performed a quasi-experimental retrospective cohort study from the National Cancer Database files for women with invasive cancers of the uterus, ovary and fallopian tube, cervix, vagina, and vulva diagnosed from 2008 to 2016. Using a marker for state Medicaid expansion status, we created difference-in-difference models to assess the impact of Medicaid expansion on the outcomes of access to and timeliness of care. We excluded women aged <40 years owing to the suppression of the state Medicaid expansions status in the data and women aged ≥65 years owing to the universal Medicare coverage availability. Our primary outcome was the rate of uninsurance at diagnosis. Secondary outcomes included Medicaid coverage, early-stage diagnosis, treatment at an academic facility, and any treatment or surgery within 30 days of diagnosis. Models were run within multiple subgroups and on a propensity-matched cohort to assess the robustness of the treatment estimates. The assumption of parallel trends was assessed with event study time plots. Our sample included 335,063 women. Among this cohort, 121,449 were from nonexpansion states and 213,614 were from expansion states, with 79,886 posttreatment cases diagnosed after the expansion took full effect in expansion states. The groups had minor differences in demographics, and we found occasional preperiod event study coefficients diverging from the mean, but the outcome trends were generally similar between the expansion and nonexpansion states in the preperiod, satisfying the necessary assumption for the difference-in-difference analysis. In a basic difference-in-difference model, the Medicaid expansion in January 2014 was associated with significant increases in insurance at diagnosis, treatment at an academic facility, and treatment within 30 days of diagnosis (P<.001 for all). In an adjusted model including all states and accounting for variable expansion implementation time, there was a significant treatment effect of Medicaid expansion on the reduction in uninsurance at diagnosis (-2.00%; 95% confidence interval, -2.3 to -1.7; P<.001), increases in early-stage diagnosis (0.80%; 95% confidence interval, 0.2-1.4; P=.02), treatment at an academic facility (0.83%; 95% confidence interval, 0.1-1.5; P=.02), treatment within 30 days (1.62%; 95% confidence interval, 1.0-2.3; P<.001), and surgery within 30 days (1.54%; 95% confidence interval, 0.8-2.3; P<.001). In particular, large gains were estimated for women living in low-income zip codes, Hispanic women, and women with cervical cancer. Estimates from the subgroup and propensity-matched cohorts were generally consistent for all outcomes besides early-stage diagnosis and treatment within 30 days. Medicaid expansion was significantly associated with gains in the access and timeliness of treatment for nonelderly women with gynecologic cancer. The implementation of Medicaid expansion could greatly benefit women in nonexpansion states. Gynecologists and gynecologic oncologists should advocate for Medicaid expansion as a means of improving outcomes and reducing socioeconomic and racial disparities.

The rapid adoption of opportunistic salpingectomy at the time of hysterectomy for benign gynecologic disease in the United States

Mounting evidence for the role of distal fallopian tubes in the pathogenesis of epithelial ovarian cancer has led to opportunistic salpingectomy being increasingly performed at the time of benign gynecologic surgery. Opportunistic salpingectomy has now been recommended as best practice in the United States to reduce future risk of ovarian cancer even in low-risk women. Preliminary analyses have suggested that performance of opportunistic salpingectomy is increasing. To examine trends in opportunistic salpingectomy in women undergoing benign hysterectomy and to determine how the publication of the tubal hypothesis in 2010 may have contributed to these trends. This is a population-based, retrospective, observational study examining the National Inpatient Sample between January 2001 and September 2015. Women younger than 50 years who underwent inpatient hysterectomy for benign gynecologic disease were grouped as hysterectomy alone vs hysterectomy with opportunistic salpingectomy. All women had ovarian conservation, and those with adnexal pathology were excluded. Linear segmented regression with log transformation was used to assess temporal trends. An interrupted time-series analysis was then used to assess the impact of the 2010 publication of the tubal hypothesis on opportunistic salpingectomy trends. A regression-tree model was constructed to examine patterns in the use of opportunistic salpingectomy. A binary logistic regression model was then fitted to identify independent characteristics associated with opportunistic salpingectomy. Sensitivity analysis was performed in women aged 50-65 years to further assess surgical trends in a wider age group. There were 98,061 (9.0%) women who underwent hysterectomy with opportunistic salpingectomy and 997,237 (91.0%) women who underwent hysterectomy alone without opportunistic salpingectomy. The rate at which opportunistic salpingectomy was being performed gradually increased from 2.4% to 5.7% between 2001 and 2010 (2.4-fold increase; P<.001), predicting a 7.0% rate of opportunistic salpingectomy in 2015. However, in 2010, the rate of opportunistic salpingectomy began to increase substantially and reached 58.4% by 2015 (10.2-fold increase; P<.001). In multivariable analysis, the largest change in the performance of opportunistic salpingectomy occurred after 2010 (adjusted odds ratio, 5.42; 95% confidence interval, 5.34-5.51; P<.001). In a regression-tree model, women who had a hysterectomy at urban teaching hospitals in the Midwest after 2013 had the highest chance of undergoing opportunistic salpingectomy during benign hysterectomy (76.4%). In the sensitivity analysis of women aged 50-65 years, a similar exponential increase in opportunistic salpingectomy was observed from 5.8% in 2010 to 55.8% in 2015 (9.8-fold increase; P<.001). Our study suggests that clinicians in the United States rapidly adopted opportunistic salpingectomy at the time of benign hysterectomy following the publication of data implicating the distal fallopian tubes in ovarian cancer pathogenesis in 2010. By 2015, nearly 60% of women had undergone opportunistic salpingectomy at benign hysterectomy.

Clinical and molecular risk factors for repeat interventions due to symptomatic uterine leiomyomas

Repeat leiomyoma occurrence or even reintervention is common after myomectomy. Little is known about the factors related to repeat interventions. This study aimed to determine the frequency of leiomyoma-related reintervention after an initial laparoscopic or abdominal myomectomy and to analyze both clinical and molecular risk factors for reinterventions. Another objective was to define the frequency of clonally related tumors from repeat operations. This retrospective cohort study included 234 women who had undergone laparoscopic or abdominal myomectomy in 2009 to 2014. Information on repeat leiomyoma-related interventions as well as on other clinical factors was collected from medical records after a median follow-up time of 11.4 years (range 7.9-13.8 years) after the index procedure. The effect of clinical risk factors on the risk of reintervention was analyzed by the Kaplan-Meier estimator and the Cox proportional hazards model. For molecular analyses, we examined the mutation profiles of 133 formalin-fixed paraffin-embedded leiomyoma samples from 33 patients with repeat operations. We screened the tumors for the 3 primary leiomyoma driver alterations-mediator complex subunit 12 mutations, high mobility group AT-hook 2 overexpression, and fumarate hydratase-deficiency-utilizing Sanger sequencing and immunohistochemistry. To further assess the clonal relationship of the tumors, we executed whole-exome sequencing for 52 leiomyomas from 21 patients who exhibited the same driver alteration in tumors obtained from multiple procedures. Reintervention rate at 11.4 years after myomectomy was 20% (46/234). Number of leiomyomas removed at the index myomectomy was a risk factor (hazard ratio 1.21; 95% confidence interval 1.09-1.34). Age at index myomectomy (hazard ratio 0.94; 95% confidence interval 0.89-0.99) and postoperative parity (hazard ratio 0.23; 95% confidence interval 0.09-0.60) were protective factors. Molecular characterization of tumors from index and nonindex operations confirmed a clonal relationship of the tumors in 3/33 (9%) patients. None of the leiomyomas harboring a mediator complex subunit 12 mutation-the most common leiomyoma driver-were confirmed clonally related. Fumarate hydratase-deficiency was detected in repeat leiomyomas from 3/33 (9%) patients. All these patients harbored a germline fumarate hydratase mutation, which is distinctive for the hereditary leiomyomatosis and renal cell cancer syndrome. Finally, we identified 3 (3/33; 9%) patients with 2 tumors each displaying somatic mutations in a recently identified novel leiomyoma driver gene, YEATS domain-containing protein 4. All YEATS domain-containing protein 4 mutations were different and thus the tumors were not clonally related. Our study shows that reintervention is common after surgical myomectomy. Uterine leiomyomas typically develop independently, but some share a clonal origin. Repeat leiomyoma occurrence may be due to genetic predisposition, such as a germline fumarate hydratase mutation. Distinct somatic YEATS domain-containing protein 4 mutations identified in multiple leiomyomas from the same patient indicate a possible role for YEATS domain-containing protein 4 in repeat leiomyomas.

Approach to radical hysterectomy for cervical cancer after the Laparoscopic Approach to Cervical Cancer trial and associated complications: a National Surgical Quality Improvement Program study

The Laparoscopic Approach to Cervical Cancer study results revolutionized our understanding of the best surgical management for this disease. After its publication, the guidelines state that the standard and recommended approach for radical hysterectomy is an open abdominal approach. Nevertheless, the effect of the Laparoscopic Approach to Cervical Cancer trial on real-world changes in the surgical approach to radical hysterectomy remains elusive. This study aimed to investigate the trends and routes of radical hysterectomy and to evaluate postoperative complication rates before and after the Laparoscopic Approach to Cervical Cancer trial (2018). The National Surgical Quality Improvement Program registry was used to examine radical hysterectomy for cervical cancer performed between 2012 and 2022. This study excluded vaginal radical hysterectomies and simple hysterectomies. The primary outcome measures were the trends in the route of surgery (minimally invasive surgery vs laparotomy) and surgical complication rates, stratified by periods before and after the publication of the Laparoscopic Approach to Cervical Cancer trial in 2018 (2012-2017 vs 2019-2022). The secondary outcome measure was major complications associated specifically with the different routes of surgery. Of the 3611 patients included, 2080 (57.6%) underwent laparotomy, and 1531 (42.4%) underwent minimally invasive radical hysterectomy. There was a significant increase in the minimally invasive surgery approach from 2012 to 2017 (45.6% in minimally invasive surgery in 2012 to 75.3% in minimally invasive surgery in 2017; P<.01) and a significant decrease in minimally invasive surgery from 2018 to 2022 (50.4% in minimally invasive surgery in 2018 to 11.4% in minimally invasive surgery in 2022; P<.001). The rate of minor complications was lower in the period before the Laparoscopic Approach to Cervical Cancer trial than after the trial (317 [16.9%] vs 288 [21.3%], respectively; P=.002). The major complication rates were similar before and after the Laparoscopic Approach to Cervical Cancer trial (139 [7.4%] vs 78 [5.8%], respectively; P=.26). The rates of blood transfusions and superficial surgical site infections were lower in the period before the Laparoscopic Approach to Cervical Cancer trial than in the period after the trial (137 [7.3%] vs 133 [9.8%] [P=.012] and 20 [1.1%] vs 53 [3.9%] [P<.001], respectively). In a comparison of minimally invasive surgery vs laparotomy radical hysterectomy during the entire study period, patients in the minimally invasive surgery group had lower rates of minor complications than in those in the laparotomy group (190 [12.4%] vs 472 [22.7%], respectively; P<.001), and the rates of major complications were similar in both groups (100 [6.5%] in the minimally invasive surgery group vs 139 [6.7%] in the laparotomy group; P=.89). In a specific complications analysis, the rates of blood transfusion and superficial surgical site infections were lower in the minimally invasive surgery group than in the laparotomy group (2.4% vs 12.7% and 0.6% vs 3.4%, respectively; P<.001; for both comparisons), and the rate of deep incisional surgical site infections was lower in the minimally invasive surgery group than in the laparotomy group (0.2% vs 0.7%, respectively; P=.048). In the multiple logistic regression analysis, the route of radical hysterectomy was not independently associated with the occurrence of major complications (adjusted odds ratio, 1.02; 95% confidence interval, 0.63-1.65). Although the proportion of minimally invasive radical hysterectomies decreased abruptly after the Laparoscopic Approach to Cervical Cancer trial, there was no change in the rate of major postoperative complications. In addition, the hysterectomy route was not associated with major postoperative complications.

Dermoid cyst management and outcomes: a review of over 1000 cases at a single institution

Mature cystic teratomas represent nearly 60% of benign ovarian neoplasms across all age groups. This study aimed to update existing descriptive studies of ovarian teratomas, including the epidemiology, rate of torsion or malignancy, and treatment modalities in a large modern cohort of patients. This was a retrospective cross-sectional study of all pathology-confirmed cases of ovarian teratoma that underwent surgery at 1 tertiary care institution from 2004 to 2015. Patient demographics, ovarian cyst characteristics, surgical approach and timing, rate of spillage, and surgical complications were examined. A total of 1054 cases of ovarian teratoma were identified during the study period. There were 113 cases (10.7%) of bilateral teratoma. The mean age at diagnosis was 38 years. The average cyst size was 6.26 cm. The overall rate of torsion was 5.6%, with a higher rate of torsion with increasing cyst size. More than 70% of cases were treated with minimally invasive surgery, which was associated with decreased perioperative complications but an increased risk of cyst spillage. Among 394 patients with cyst spillage, only 1 patient developed chemical peritonitis. The malignant transformation rate of mature cystic teratoma in this cohort was 1.1%. This cohort included 100 pregnant women with mature teratoma. Pregnant patients were more likely to have minimally invasive surgery in the first trimester of pregnancy and more likely to undergo laparotomy in the second or third trimester of pregnancy. Similar rates of bilaterality, torsion, malignant transformation, and struma ovarii in ovarian teratomas were found in this large modern cohort compared with previous literature. Most cases of ovarian teratoma can be managed laparoscopically, which is associated with a lower surgical complication rate. Despite the increased risk of cyst spillage with a minimally invasive approach, chemical peritonitis is a rare complication.

Benefit and burden in the Dutch cytology-based vs high-risk human papillomavirus-based cervical cancer screening program

In 2017, the Dutch cervical cancer screening program had replaced the primary cytology-based screening with primary high-risk human papillomavirus-based screening, including the opportunity to participate through self-sampling. Evaluation and balancing benefit (detection of high-grade cervical intraepithelial neoplasia) and burden of screening (unnecessary referrals, invasive diagnostics, and overtreatment) is needed. This study aimed to compare the referral rates, detection of high-grade cervical intraepithelial neoplasia, overdiagnosis, and overtreatment in the new high-risk human papillomavirus-based screening program, including physician-sampled and self-sampled material, with the previous cytology-based screening program in the Netherlands. A retrospective cohort study was conducted within the Dutch population-based cervical cancer screening program. Screenees with referrals for colposcopy between 2014 and 2015 (cytology-based screening) and 2017 and 2018 (high-risk human papillomavirus-based screening) were included. Data were retrieved from the Dutch Pathology Registry (PALGA) and compared between the 2 screening programs. The main outcome measures were referral rate, detection of high-grade cervical intraepithelial neoplasia or worse, overdiagnosis (cervical intraepithelial neoplasia grade 1 or less in the histologic specimen), and overtreatment (cervical intraepithelial neoplasia grade 1 or less in the treatment specimen). Of the women included in the study, 19,109 received cytology-based screening, and 26,171 received high-risk human papillomavirus-based screening. Referral rates increased from 2.5% in cytology-based screening to 4.2% in high-risk human papillomavirus-based screening (+70.2%). Detection rates increased to 46.2% for cervical intraepithelial neoplasia grade 2 or worse, 32.2% for cervical intraepithelial neoplasia grade 3 or worse, and 31.0% for cervical cancer, and overdiagnosis increased to 143.4% with high-risk human papillomavirus-based screening. Overtreatment rates were similar in both screening periods. The positive predictive value of referral for detection of cervical intraepithelial neoplasia grade 2 or worse in high-risk human papillomavirus-based screening was 34.6% compared with 40.2% in cytology-based screening. Women screened through self-sampling were at higher risk of cervical intraepithelial neoplasia grade 2 or worse detection (odds ratio, 1.38; 95% confidence interval, 1.20-1.59) and receiving treatment (odds ratio, 1.31; 95% confidence interval, 1.16-1.48) than those screened through physician-sampling. Compared with cytology-based screening, high-risk human papillomavirus-based screening increases detection of high-grade cervical intraepithelial neoplasia, with 462 more cervical intraepithelial neoplasia grade 2 or worse cases per 100,000 women but at the expense of 850 more cases per 100,000 women with invasive diagnostics indicating cervical intraepithelial neoplasia grade 1 or less.

Cost of care for the initial management of cervical cancer in women with commercial insurance

Women with newly diagnosed cervical cancer are often treated with extensive, multimodal therapies that may include a combination of surgery, radiation, and chemotherapy. Little is known about the cost of treatment or how these costs are passed on to the patients. The objectives of this study were to examine the cost of care during the first year after a diagnosis of cervical cancer, to estimate the sources of the costs, and to explore the out-of-pocket costs. We performed a study of women with commercial insurance who received a new diagnosis of cervical cancer, and whose cases were recorded in the MarketScan database from 2008 to 2016. Patients were categorized based on the primary treatment received being either surgery (hysterectomy with or without adjuvant radiation or chemotherapy) or radiation. The inflation-adjusted medical expenditures for a 12-month period beginning on the date of the first treatment were estimated. The payments were divided into the expenditures of inpatient care, outpatient care (including chemotherapy), and outpatient pharmacy costs. The out-of-pocket costs incurred by the patients in the form of copayments, coinsurance, and deductibles were estimated. A total of 4495 patients, including 3014 (67%) who underwent surgery and 1481 (33%) who primarily underwent radiotherapy, were identified. The median total expenditure per patient during the first year after the diagnosis was $56,250 (interquartile range, $25,767-$107,532). The median total expenditure for patients with surgery as the primary treatment was $37,222 (interquartile range, $20,957-$75,555). The median total expenditure for patients treated primarily with radiotherapy was $101,266 (interquartile range, $63,155-$160,760). For patients treated primarily with surgery, inpatient services accounted for $15,145 (interquartile range, $0-$26,898), outpatient services accounted for $18,430 (interquartile range, $5354-$48,047), and outpatient pharmacy costs accounted for $628 (interquartile range, $141-$1847). The median cost for those women who did not require adjuvant therapy was $26,164 compared with $89,760 for women treated with adjuvant radiation. The median out-of-pocket costs for the cohort was $2253 (interquartile range, $1137-$3990) or 3.9% of the total costs. The cost of care for women with newly diagnosed cervical cancer is substantial. Overall, patients are responsible for approximately 3.9% of the costs in the form of out-of-pocket expenditures.

A prospective study of treatments for cervical intraepithelial neoplasia and fecundability

Treatments for cervical intraepithelial neoplasia remove precancerous cells from the cervix by excising or ablating the transformation zone. Most studies show no association between cervical intraepithelial neoplasia treatments and fertility outcomes. However, only 2 studies have examined time to pregnancy, both using retrospective study designs, with 1 study showing no association and the other showing a 2-fold increased risk of infertility (time to pregnancy >12 months) following excisional or ablative treatment. We examined the association between cervical intraepithelial neoplasia treatments and fecundability. We analyzed data from Pregnancy Study Online (PRESTO), a prospective cohort study of North American pregnancy planners enrolled during 2013-2019. At baseline, women reported whether they ever had an abnormal Papanicolaou test result, the number of abnormal Papanicolaou test results, and their age at first abnormal Papanicolaou test result. They also reported whether they underwent diagnostic (colposcopy) or treatment (excisional or ablative) procedures, and their age at each procedure. We restricted analyses to 8017 women with 6 or fewer cycles of attempt time at enrollment who reported receiving a Papanicolaou test in the previous 3 years. We estimated fecundability ratios and 95% confidence intervals using proportional probabilities models adjusted for sociodemographics, healthcare use, smoking, number of sexual partners, history of sexually transmitted infections, and human papillomavirus vaccination. A history of abnormal Papanicolaou test results showed little association with fecundability (fecundability ratio, 1.00; 95% confidence interval, 0.95-1.06). Likewise, receipt of colposcopy or treatment procedures, and time since treatment were not materially associated with fecundability. Results were similar when stratified by age and smoking status. We observed no appreciable association of self-reported history of abnormal Papanicolaou test results, colposcopy, treatments for cervical intraepithelial neoplasia, or recency of treatment with fecundability. These results agree with the majority of previous studies in indicating little effect of cervical intraepithelial neoplasia treatments on future fertility.

Assessing the comparative efficacy of sentinel lymph node detection techniques in vulvar cancer: a systematic review and meta-analysis

Vulvar cancer is a rare gynecologic malignancy where lymph node status is the most important prognostic factor. Sentinel lymph node biopsy has replaced complete lymphadenectomy in early-stage disease due to its accuracy and lower morbidity. Although technetium-99m combined with blue dye or indocyanine green is the current standard, emerging tracers like indocyanine green alone and superparamagnetic iron oxide show comparable detection rates with potential logistical advantages. This systematic review compares the detection rates of different sentinel lymph node detection methods, such as, technetium-99m, blue dye, indocyanine green, and superparamagnetic iron oxide in vulvar cancer. A systematic search of PubMed, Scopus, Embase, MEDLINE, and Web of Science was conducted up to August 2024. Eligible studies included randomized controlled trials and observational studies evaluating sentinel lymph node detection in vulvar cancer. Our analysis included observational and randomized controlled trials. The following population-intervention-comparison-outcome framework was used: P-female patients diagnosed with vulvar cancer undergoing sentinel lymph node biopsy as part of their diagnostic or therapeutic management. I-technetium-99m, indocyanine green, superparamagnetic iron oxide, blue dye, technetium-99m+blue dye, technetium-99m+indocyanine green. C-technetium-99m, indocyanine green, superparamagnetic iron oxide, blue dye, technetium-99m+blue dye, technetium-99m+indocyanine green. O-primary outcome: detection rates. To address heterogeneity in study populations, we used a frequentist random-effects model with 95% confidence intervals for effect size. A three-level multivariate model accounted for correlations in studies examining 1 or multiple methods. Classical two-level meta-analyses were performed to assess publication bias, with Funnel plots and Peters test used for bias detection. The Risk Of Bias In Non-randomised Studies - of Interventions and Risk of Bias 2 tools were utilized to assess bias across various domains, while GRADEpro was employed to evaluate the certainty of evidence. A total of 88 studies comprising 4637 patients were included. Per-patient detection rates were as follows: blue dye 78% (95% confidence interval, 69%; 85%), indocyanine green 88% (95% confidence interval, 76%-95%), superparamagnetic iron oxide 95% (95% confidence interval, 81%-99%), technetium-99m 92% (95% confidence interval, 87%-95%), technetium-99m+blue dye 94% (95% confidence interval, 91%-96%), and technetium-99m+indocyanine green 96% (95% confidence interval , 90%-99%). Per-groin detection rates indicated similar trends calculated with three-level forest plots, indocyanine green, and technetium-99m achieving 87% and 93% when combined. Per-groin detection rate of technetium-99m+blue dye resulted in 87% (95% confidence interval, 83%-91%). Superparamagnetic iron oxide exhibited the second highest per-patient detection rate but lacked sufficient per-groin data. Indocyanine green provides detection rates comparable to technetium-99m combined with blue dye or indocyanine green, with fewer logistical constraints, while superparamagnetic iron oxide shows remarkable potential but requires further validation in larger, diverse cohorts. These findings suggest that single use of indocyanine green could replace technetium-99m and indocyanine green or blue dye in sentinel lymph node mapping for vulvar cancer, and superparamagnetic iron oxide offers promising detection rates over radioactive isotopes.

Colposcopic and histopathologic evaluation of women with HPV persistence exiting an organized screening program

Human papillomavirus-based screening has a higher sensitivity for precursors of cervical cancer compared with cytology-based screening. However, more evidence is needed on optimal management of human papillomavirus-positive women. The objective of the study was to compare the risk of histopathologically confirmed cervical intraepithelial lesions grade 2 or worse after 1 and 3 years of human papillomavirus persistence, respectively, and evaluate the clinical management of human papillomavirus-positive women in the 56-60 year age group. This was a randomized health care policy offering human papillomavirus screening to 50% of resident women aged 56-60 years in the Stockholm/Gotland region of Sweden during January 2012 through May 2014. Women who were human papillomavirus positive/cytology negative at baseline were referred for a repeat test after 1 or 3 years. In case of human papillomavirus persistence, women were referred for colposcopy, including biopsies and endocervical sampling. The human papillomavirus prevalence was 5.5% (405 women of 7325 attending). Among the 405 human papillomavirus-positive women, 313 were reflex test cytology negative at baseline and were referred for a repeat human papillomavirus test, 176 women after 1 year and 137 women after 3 years. After 1 year, 91 of 176 (52%) were persistently human papillomavirus positive and after 3 years 55 of 137 (40%) (P = .042). In repeat cytology, 10 of the 91 (12%) were positive after 1 year and 15 of 55 (33%) after 3 years (P = .005). The attendance rates for colposcopy were similar: 82 of 91 (90%) in the 1 year group and 45 of 55 (82%) in the 3 year group. All women attending colposcopy were postmenopausal, and endocervical sampling and punch biopsies were performed to facilitate colposcopic management, with a positive predictive value of 43-50% and 28-31%, respectively. Histopathologically confirmed cervical intraepithelial lesions grade 2 or worse was found in 19 of 82 women (23%) and 9 of 45 women (20%) in the 1 year and 3 year groups, respectively, and registry linkage follow-up found no cancers in either group. Human papillomavirus genotyping was predictive of cervical intraepithelial lesions grade 2 or worse, and human papillomavirus 16 was the most common genotype at human papillomavirus persistence, occurring in 18% of the cases in the 1 year group and 20% in the 3 year group. It was safe to postpone repeat human papillomavirus tests for 3 years in postmenopausal women attending the organized cervical screening program. There was a high risk for cervical intraepithelial lesions grade 2 or worse at follow-up and noteworthy yields from human papillomavirus genotyping as well as endocervical sampling and random biopsies in the absence of visible colposcopic lesions.

Formal assessment of the learning curve for minimally invasive methods is vital in retrospective cohort studies

Incomplete excision of cervical intraepithelial neoplasia as a predictor of the risk of recurrent disease—a 16-year follow-up study

Women treated for high-grade cervical intraepithelial neoplasia (grade 2 or 3) are at elevated risk for developing cervical cancer. Suggested factors identifying women at highest risk for recurrence post-therapeutically include incomplete lesion excision, lesion location, size and severity, older age, treatment modality, and presence of high-risk human papilloma virus after treatment. This question has been intensively investigated over decades, but there is still substantial debate as to which of these factors or combination of factors most accurately predict treatment failure. In this study, we examine the long-term risk of residual/recurrent high-grade cervical intraepithelial neoplasia among women previously treated for cervical intraepithelial neoplasia 2/3 and how this varies according to margin status (considering also location), as well as comorbidity (conditions assumed to interact with high-risk human papilloma virus acquisition and/or cervical intraepithelial neoplasia progression), posttreatment presence of high-risk human papilloma virus, and other factors. This prospective study included 991 women with histopathologically confirmed cervical intraepithelial neoplasia 2/3 who underwent conization in 2000-2007. Information on the primary histopathologic finding, treatment modality, comorbidity, age, and high-risk human papilloma virus status during follow-up, and residual/recurrent high-grade cervical intraepithelial neoplasia was obtained from the Swedish National Cervical Screening Registry and medical records. Cumulative incidence of residual/recurrent high-grade cervical intraepithelial neoplasia was plotted on Kaplan-Meier curves, with determinants assessed by Cox regression. During a median of 10 years and maximum of 16 years of follow-up, 111 patients were diagnosed with residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Women with positive/uncertain margins had a higher risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse than women with negative margins, adjusting for potential confounders (hazard ratio, 2.67; 95% confidence interval, 1.81-3.93). The risk of residual/recurrent high-grade cervical intraepithelial neoplasia or worse varied by anatomical localization of the margins (endocervical: hazard ratio, 2.72; 95% confidence interval, 1.67-4.41) and both endo- and ectocervical (hazard ratio, 4.98; 95% confidence interval, 2.85-8.71). The risk did not increase significantly when only ectocervical margins were positive or uncertain. The presence of comorbidity (autoimmune disease, human immunodeficiency viral infection, hepatitis B and/or C, malignancy, diabetes, genetic disorder, and/or organ transplant) was also a significant independent predictor of residual/recurrent high-grade cervical intraepithelial neoplasia or worse. In women with positive high-risk human papilloma virus findings during follow-up, the hazard ratio of positive/uncertain margins for recurrent/residual high-grade cervical intraepithelial neoplasia or worse increased significantly compared to that in women with positive high-risk human papilloma virus findings but negative margins. Patients with incompletely excised cervical intraepithelial neoplasia 2/3 are at increased risk for residual/recurrent high-grade cervical intraepithelial neoplasia or worse. Margin status combined with high-risk human papilloma virus results and consideration of comorbidity may increase the accuracy for predicting treatment failure.

An updated understanding of the natural history of cervical human papillomavirus infection—clinical implications

Recently, the International Papillomavirus Society convened a working group on cervical human papillomavirus latency, which resulted in an updated understanding of the human papillomavirus natural history. While the previous human papillomavirus natural history model considered human papillomavirus detection to be a result of human papillomavirus acquisition or possibly reinfection, and loss of human papillomavirus detection to be a result of viral clearance, the updated understanding of the human papillomavirus natural history is more nuanced. Thus, human papillomavirus detection may occur as a result of autoinoculation, deposition from a recent sex act, or as a redetection of a previously acquired infection. Similarly, loss of human papillomavirus detection likely reflects immune control rather than complete viral clearance. As it is practically impossible to identify the "true" source of a new human papillomavirus detection or determine why human papillomavirus is no longer detectable, we propose that healthcare providers and researchers use the terminology human papillomavirus detected vs human papillomavirus not detected. Moreover, we describe the updated understanding in a clinical context. Specifically, we discuss the potential implications of the updated understanding regarding clinical counseling in screening, recommendations on cervical screening, and human papillomavirus vaccination. We also suggest key phrases that healthcare providers may use when counseling women attending routine human papillomavirus-based cervical screening.

The Paget Trial: topical 5% imiquimod cream for noninvasive vulvar Paget disease

Vulvar Paget disease is an extremely rare skin disorder, which is most common in postmenopausal women. Most vulvar Paget disease cases are noninvasive; however, it may be invasive or associated with an underlying vulvar or distant adenocarcinoma. The current treatment of choice for noninvasive vulvar Paget disease is wide local excision, which is challenging because of extensive intraepithelial spread and may cause severe morbidity. Recurrence rates are high, ranging from 15% to 70%, which emphasizes the need for new treatment options. Imiquimod, a topical immune response modifier, has been shown to be effective in a few studies and case reports, and is a promising new treatment modality. To prospectively investigate the efficacy, safety, and effect on quality of life of a standardized treatment schedule with 5% imiquimod cream in patients with noninvasive vulvar Paget disease. The Paget Trial is a multicenter prospective observational clinical study including 7 tertiary referral hospitals in the Netherlands. A total of 24 patients with noninvasive vulvar Paget disease were treated with topical 5% imiquimod cream 3 times a week for 16 weeks. The primary efficacy outcome was the reduction in lesion size at 12 weeks after the end of treatment. Secondary outcomes were safety, clinical response after 1 year, and quality of life. Safety was assessed by evaluation of adverse events and tolerability of treatment. Quality of life was investigated with 3 questionnaires taken before, during, and after treatment. Data were available for 23 patients, 82.6% of whom responded to therapy. A complete response was reported in 12 patients (52.2%), and 7 patients (30.4%) had a partial response. A histologic complete response was observed in 10 of the 12 patients with a complete response. Patients experienced side effects such as fatigue (66.7%-70.9%) and headaches (16.7%-45.8%), and almost 80% needed painkillers during treatment. Eight patients (34.8%) adjusted the treatment protocol to 2 applications a week, and 3 patients (13.0%) stopped treatment because of side effects after 4 to 11 weeks. Treatment improved quality of life, whereas a slight, temporary negative impact was observed during treatment. Two patients with a complete response developed a recurrence within 1 year after treatment. Follow-up showed 6 patients with a noninvasive recurrence after a median of 31 months (14-46 months) after the end of treatment. Topical 5% imiquimod cream can be an effective and safe treatment alternative for noninvasive vulvar Paget disease, particularly when compared with treatment with surgical excision.

Inflammatory vulvar dermatoses following immune checkpoint inhibitor therapy

p53 and p16 expression profiles in vulvar cancer: a translational analysis by the Arbeitsgemeinschaft Gynäkologische Onkologie Chemo and Radiotherapy in Epithelial Vulvar Cancer study group

There are 2 known pathways for tumorigenesis of vulvar squamous cell carcinoma-a human papillomavirus-dependent pathway characterized by p16 overexpression and a human papillomavirus-independent pathway linked to lichen sclerosus, characterized by TP53 mutation. A correlation of human papillomavirus dependency with a favorable prognosis has been proposed. The objective of the study was to further understand the role of human papillomavirus and p53 status in vulvar squamous cell carcinoma and characterize its clinical relevance. The Arbeitsgemeinschaft Gynaecological Oncology Chemo and Radiotherapy in Epithelial Vulvar Cancer-1 study is a retrospective cohort study of 1618 patients with primary vulvar squamous cell carcinoma Fédération Internationale de Gynécologie et d'Obstétrique stage ≥1B treated at 29 gynecologic cancer centers in Germany between 1998 and 2008. For this translational substudy, formalin-fixed paraffin-embedded tissue was collected. A tissue microarray was constructed (n=652 samples); p16 and p53 expression was determined by immunohistochemistry. Human papillomavirus status and subtype were analyzed by polymerase chain reaction. p16 immunohistochemistry was positive in 166 of 550 tumors (30.2%); p53 staining in 187 of 597 tumors (31.3%). Only tumors with available information regarding p16 and p53 immunohistochemistry and without p53 silent expression pattern were further analyzed (n=411); 3 groups were defined: p53+ (n=163), p16+/p53- (n=132), and p16-/p53- (n=116). Human papillomavirus DNA was detected in 85.6% of p16+/p53- tumors; human papillomavirus-16 was the most common subtype (86.3%). Patients with p16+ tumors were younger (64 vs 72 years for p53+, respectively, 69 years for p16-/p53- tumors; P<.0001) and showed lower rates of lymph-node involvement (28.0% vs 42.3% for p53+, respectively, 30.2% for p16-/p53- tumors; P=.050). Notably, 2-year-disease-free and overall survival rates were significantly different among the groups: disease-free survival, 47.1% (p53+), 60.2% (p16-/p53-), and 63.9% (p16+/p53-) (P<.001); overall survival, 70.4% (p53+), 75.4% (p16-/p53-), and 82.5% (p16+/p53-) (P=.002). In multivariate analysis, the p16+/p53- phenotype showed a consistently improved prognosis compared with the other groups (hazard ratio, 0.66; 95% confidence interval, 0.44-0.99; P=.042). p16 overexpression is associated with an improved prognosis whereas p53 positivity is linked to an adverse outcome. Our data support the hypothesis of a clinically relevant third subgroup of vulvar squamous cell carcinoma with a p53-/p16- phenotype showing an intermediate prognosis that needs to be further characterized.

A clinical ultrasound algorithm to identify uterine sarcoma and smooth muscle tumors of uncertain malignant potential in patients with myometrial lesions: the MYometrial Lesion UltrasouNd And mRi study

Differential diagnosis between benign uterine smooth muscle tumors and malignant counterpart is challenging. To evaluate the accuracy of a clinical and ultrasound based algorithm in predicting mesenchymal uterine malignancies, including smooth muscle tumors of uncertain malignant potential. We report the 12-month follow-up of an observational, prospective, single-center study that included women with at least 1 myometrial lesion ≥3 cm on ultrasound examination. These patients were classified according to a 3-class diagnostic algorithm, using symptoms and ultrasound features. "White" patients underwent annual telephone follow-up for 2 years, "Green" patients underwent a clinical and ultrasound follow-up at 6, 12, and 24 months and "Orange" patients underwent surgery. We further developed a risk class system to stratify the malignancy risk. Two thousand two hundred sixty-eight women were included and target lesion was classified as benign in 2158 (95.1%), as other malignancies in 58 (2.6%) an as mesenchymal uterine malignancies in 52 (2.3%) patients. At multivariable analysis, age (odds ratio 1.05 [95% confidence interval 1.03-1.07]), tumor diameter >8 cm (odds ratio 5.92 [95% confidence interval 2.87-12.24]), irregular margins (odds ratio 2.34 [95% confidence interval 1.09-4.98]), color score=4 (odds ratio 2.73 [95% confidence interval 1.28-5.82]), were identified as independent risk factors for malignancies, whereas acoustic shadow resulted in an independent protective factor (odds ratio 0.39 [95% confidence interval 0.19-0.82[). The model, which included age as a continuous variable and lesion diameter as a dichotomized variable (cut-off 81 mm), provided the best area under the curve (0.87 [95% confidence interval 0.82-0.91]). A risk class system was developed, and patients were classified as low-risk (predictive model value <0.39%: 0/606 malignancies, risk 0%), intermediate risk (predictive model value 0.40%-2.2%: 9/1093 malignancies, risk 0.8%), high risk (predictive model value ≥2.3%: 43/566 malignancies, risk 7.6%). The preoperative 3-class diagnostic algorithm and risk class system can stratify women according to risk of malignancy. Our findings, if confirmed in a multicenter study, will permit differentiation between benign and mesenchymal uterine malignancies allowing a personalized clinical approach.

Endocervical sampling in women with suspected cervical neoplasia: a systematic review and meta-analysis of diagnostic test accuracy studies

Endocervical sampling in women with suspected cervical neoplasia can be performed by either endocervical brush or endocervical curettage. This study aimed to estimate the diagnostic accuracy, discomfort, and number of inadequate samples with either test. Four bibliographic databases were searched on June 9, 2022, with no date or language restrictions. We included all diagnostic studies and randomized clinical trials that compared the endocervical brush with endocervical curettage in women with an indication for colposcopy. The review protocol was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42021222406). Two authors independently screened studies, extracted data, performed the risk-of-bias assessment (Quality Assessment of Diagnostic Accuracy Studies-2), and rated the certainty of the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. A meta-analysis of diagnostic test accuracy was performed using a bivariate random-effects model. We included 7 studies: 4 diagnostic cohort studies and 3 randomized clinical trials. The reference standard was conization or hysterectomy. Risk of bias and concern about applicability were high for some of the studies in patient selection and flow and timing. Overall pooled sensitivity was 81% (95% confidence interval, 48-95; 799 women; 7 studies; low quality of evidence) for endocervical brush and 70% (95% confidence interval, 42-89; 761 women; 7 studies; low quality of evidence) for endocervical curettage. Overall pooled specificity was 73% (95% confidence interval, 36-93; 799 women; 7 studies; low quality of evidence) for endocervical brush and 81% (95% confidence interval, 56-94; 761 women; 7 studies; low quality of evidence) for endocervical curettage. The risk ratio for inadequate samples with endocervical curettage compared with endocervical brush was 2.53 (95% confidence interval, 0.58-11.0; P=.215; low-certainty evidence). Two studies reported on patient discomfort; one found less discomfort in the endocervical brush group, and the other found no difference. No difference was found between endocervical brush and endocervical curettage in diagnostic accuracy, inadequate sampling rate, and adverse effects based on low-quality of evidence. Variation in the characteristics of women and the resulting diagnostic pathways make the external validity limited.

Risk of endometrial cancer in asymptomatic postmenopausal women in relation to ultrasonographic endometrial thickness

African ancestry is associated with aggressive endometrial cancer

Impact of hormonal biomarkers on response to hormonal therapy in advanced and recurrent endometrial cancer

Approximately 20% of women with endometrial cancer have advanced-stage disease or suffer from a recurrence. For these women, prognosis is poor, and palliative treatment options include hormonal therapy and chemotherapy. Lack of predictive biomarkers and suboptimal use of existing markers for response to hormonal therapy have resulted in overall limited efficacy. This study aimed to improve the efficacy of hormonal therapy by relating immunohistochemical expression of estrogen and progesterone receptors and estrogen receptor pathway activity scores to response to hormonal therapy. Patients with advanced or recurrent endometrial cancer and available biopsies taken before the start of hormonal therapy were identified in 16 centers within the European Network for Individualized Treatment in Endometrial Cancer and the Dutch Gynecologic Oncology Group. Tumor tissue was analyzed for estrogen and progesterone receptor expressions and estrogen receptor pathway activity using a quantitative polymerase chain reaction-based messenger RNA model to measure the activity of estrogen receptor-related target genes in tumor RNA. The primary endpoint was response rate defined as complete and partial response using the Response Evaluation Criteria in Solid Tumors. The secondary endpoints were clinical benefit rate and progression-free survival. Pretreatment biopsies with sufficient endometrial cancer tissue and complete response evaluation were available in 81 of 105 eligible cases. Here, 22 of 81 patients (27.2%) with a response had estrogen and progesterone receptor expressions of >50%, resulting in a response rate of 32.3% (95% confidence interval, 20.9-43.7) for an estrogen receptor expression of >50% and 50.0% (95% confidence interval, 35.2-64.8) for a progesterone receptor expression of >50%. Clinical benefit rate was 56.9% for an estrogen receptor expression of >50% (95% confidence interval, 44.9-68.9) and 75.0% (95% confidence interval, 62.2-87.8) for a progesterone receptor expression of >50%. The application of the estrogen receptor pathway test to cases with a progesterone receptor expression of >50% resulted in a response rate of 57.6% (95% confidence interval, 42.1-73.1). After 2 years of follow-up, 34.3% of cases (95% confidence interval, 20-48) with a progesterone receptor expression of >50% and 35.8% of cases (95% confidence interval, 20-52) with an estrogen receptor pathway activity score of >15 had not progressed. The prediction of response to hormonal treatment in endometrial cancer improves substantially with a 50% cutoff level for progesterone receptor immunohistochemical expression and by applying a sequential test algorithm using progesterone receptor immunohistochemical expression and estrogen receptor pathway activity scores. However, results need to be validated in the prospective Prediction of Response to Hormonal Therapy in Advanced and Recurrent Endometrial Cancer (PROMOTE) study.

Mismatch repair status influences response to fertility-sparing treatment of endometrial cancer

Patients younger than 40 years usually present with early-stage endometrial cancer with favorable prognosis. However, such patients are usually in their childbearing age and may desire fertility-sparing options. The identification of biomarkers may improve the clinical outcomes in these patients and aid in fertility-sparing management; however, there has been no reports on biomarker analysis so far. This study aimed to evaluate the prognostic significance of Proactive Molecular Risk Classifier for Endometrial Cancer in the fertility-sparing management of endometrial cancer. A total of 57 endometrial biopsy specimens obtained before hormone therapy were evaluated, and patients were classified according to the Proactive Molecular Risk Classifier for Endometrial Cancer molecular subtypes (mismatch repair deficiency, DNA polymerase epsilon mutation, wild-type p53, and abnormal p53). The primary endpoint was the response rate after hormone therapy. The secondary endpoint was the recurrence rate after the complete response, hysterectomy rate owing to treatment failure, and upstaged diagnosis rate after hysterectomy. Of 57 patients, 9 (15.8%) had mismatch repair deficiency, 2 (3.5%) had DNA polymerase epsilon mutation, 45 (78.9%) had wild-type p53, and 1 (1.8%) had abnormal p53. Overall, the complete response rate was 75.4% after hormone therapy. Patients with mismatch repair deficiency had a significantly lower complete response or partial response rate than those with wild-type p53 in terms of the best overall response (44.4% [95% confidence interval, 4.0-85.0] vs 82.2% [95% confidence interval, 71.0-94.0]; P=.018) and complete response rate at 6 months (11.1% [95% confidence interval, 0.2-37.0] vs 53.3% [95% confidence interval, 38.0-68.0]; P=.010). Among patients with mismatch repair deficiency, 4 underwent immediate hysterectomy because of treatment failure and 3 presented upstaged diagnosis after hysterectomy. The Proactive Molecular Risk Classifier for Endometrial Cancer molecular classification has prognostic significance in the fertility-sparing management of endometrial cancer, thereby enabling early stratification and risk assignment to direct care. Mismatch repair status could be used as a predictive biomarker for selecting patients who could benefit from hormone therapy. These findings need to be validated in larger studies.