Jason D Wright

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.

Stage IC grade 1 endometrioid adenocarcinoma of the ovary: assessment of post-operative chemotherapy de-escalation

Given limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1 endometrioid ovarian carcinoma, this population-based study examined the association between post-operative chemotherapy and overall survival in this tumor group. The National Cancer Institute's Surveillance, Epidemiology, and End Results program was retrospectively queried. The study population was 1207 patients with stage IC grade 1-3 endometrioid ovarian carcinoma who received primary cancer-directed surgery from 2007 to 2020. Overall survival was assessed with multivariable Cox proportional hazard regression model. The median age was 52, 54, and 55 years for grade 1, 2, and 3 groups, respectively (p=0.02). Grade 1 and 2 tumors were more common than grade 3 tumors (n=508 (42.1%), n=493 (40.8%), and n=206 (17.1%), respectively). Chemotherapy use rate for grade 1 tumors was lower compared with grade 2-3 tumors (67.9%, 76.5%, and 78.6%, respectively, p<0.001). When nodal evaluation was performed for grade 1 tumors, among patients who did not receive post-operative chemotherapy and among those who did, 5-year overall survival rate exceeded 90% (93.3% and 96.0%, respectively), with statistically non-significant hazard estimates (adjusted hazard ratio (aHR) 1.54, 95% CI 0.63 to 3.73). In contrast, post-operative chemotherapy omission for patients who did not undergo nodal evaluation was associated with decreased overall survival (5-year rates 82.3% vs 96.0%, aHR 5.41, 95% CI 1.95 to 15.06). Results were similar for node-evaluated grade 2 tumors (5-year overall survival rates, 94.6% and 94.4% for node-evaluated post-operative chemotherapy omission and administration, respectively), but not in grade 3 tumors. The results of this population-based study may partially support the current clinical practice guidelines for post-operative chemotherapy omission as a possible option for patients with stage IC grade 1 endometrioid adenocarcinoma of the ovary for those who had lymph node evaluation. Observed data were also supportive for node-evaluated grade 2 tumors, warranting further evaluation.

Levonorgestrel-releasing intrauterine device therapy vs oral progestin treatment for reproductive-aged patients with endometrial intraepithelial neoplasia: a systematic review and meta-analysis

Abstract Background We conducted a systematic review and meta-analysis to examine outcomes of patients with endometrial intraepithelial neoplasia treated with oral progestins or a levonorgestrel-releasing intrauterine device (IUD). Methods We conducted a systematic review across 5 databases to examine outcomes of progestational treatment (oral progestins or levonorgestrel-releasing IUD) for patients with endometrial intraepithelial neoplasia. The primary outcome was the best complete response rate within 12 months of primary progestational treatment. Sensitivity analyses were performed by removing studies with extreme effect sizes. Secondary outcomes included the pooled pregnancy rate. Results We identified 21 eligible studies, including 824 premenopausal patients with endometrial intraepithelial neoplasia, for our meta-analysis. Among these, 459 patients received oral progestin, and 365 patients received levonorgestrel-releasing IUD as a primary progestational treatment. The pooled best complete response proportion within 12 months was 82% (95% confidence interval [CI] = 69% to 91%) following oral progestin treatment and 95% (95% CI = 81% to 99%) following levonorgestrel-releasing IUD treatment. After removing outlier studies, the pooled proportion was 86% (95% CI = 75% to 92%) for the oral progestin group and 96% (95% CI = 91% to 99%) for the levonorgestrel-releasing IUD group, with reduced heterogeneity. The pooled pregnancy rate was 50% (95% CI = 35% to 65%) after oral progestin and 35% (95% CI = 23% to 49%) after levonorgestrel-releasing IUD treatment. Conclusions This meta-analysis provides data on the effectiveness of oral progestins and levonorgestrel-releasing IUD treatment within 12 months of treatment among premenopausal patients with endometrial intraepithelial neoplasia. Although based on small numbers, the rate of pregnancy after treatment is modest. These data may be beneficial for selecting progestational therapies that allow fertility preservation for patients with endometrial intraepithelial neoplasia.

Ambient particulate matter air pollution exposure and ovarian cancer incidence in the USA: An ecological study

AbstractObjectiveTo investigate associations between air particulate matter of ≤2.5 μm in diameter (PM2.5) and ovarian cancer.DesignCounty‐level ecological study.SettingSurveillance, epidemiology, and end results from a collection of state‐level cancer registries across 744 counties. Data from the Environmental Protection Agency's network for PM2.5 monitoring was used to calculate trailing 5‐ and 10‐year PM2.5 county‐level values. County‐level data on demographic characteristics were obtained from the American Community Survey.PopulationA total of 98 751 patients with histologically confirmed ovarian cancer as a primary malignancy from 2000 to 2016.MethodsGeneralised linear regression models were developed to estimate the association between PM2.5 and PM10 levels, over 5‐ and 10‐year periods of exposure, and ovarian cancer risk, after accounting for county‐level covariates.Main outcome measuresRisk ratios for associations between ovarian cancer (both overall and specifically epithelial ovarian cancer) and PM2.5 levels.ResultsFor the 744 counties included, the average PM2.5 level from 1990 through 2018 was 11.75 μg/m3 (SD = 3.7) and the average PM10 level was 22.7 μg/m3 (SD = 5.7). After adjusting for county‐level covariates, the overall annualised ovarian cancer incidence was significantly associated with increases in 5‐year PM2.5 (RR = 1.11 per 10 units (μg/m3) increase, 95% CI 1.06–1.16). Similarly, when the analysis was limited to epithelial cell tumours and adjusted for county‐level covariates there was a significant association with trailing 5‐year PM2.5 exposure models (RR = 1.12 per 10 units increase, 95% CI 1.08–1.17). Likewise, 10‐year PM2.5 exposure was associated with ovarian cancer overall and with epithelial ovarian cancer.ConclusionsHigher county‐level ambient PM2.5 levels are associated with 5‐ and 10‐year incidences of ovarian cancer, as measurable in an ecological study.

Dostarlimab for recurrent mismatch repair‐deficient endometrial cancer: A cost‐effectiveness study

AbstractObjectivePatients with recurrent endometrial cancer treated with carboplatin and paclitaxel whose disease progresses have few effective treatment options. Based on promising clinical trial data, the anti‐programmed cell death 1 (anti‐PD‐1) antibody dostarlimab was recently granted accelerated approval for endometrial cancer by the US Food and Drug Administration. We developed a decision model to examine the cost‐effectiveness of dostarlimab for patients with progressive/recurrent deficient mismatch repair (dMMR) endometrial cancer whose disease has progressed with first‐line chemotherapy.DesignCost‐effectiveness study.PopulationHypothetical cohort of 6000 women with progressive/recurrent dMMR endometrial cancer.MethodsThe initial decision point in the Markov model was treatment with dostarlimab, pembrolizumab or pegylated liposomal doxorubicin (PLD). Model probabilities, and cost and utility values were derived with assumptions drawn from published literature. Effectiveness was estimated as average quality‐adjusted life years (QALYs) gained. One‐way, two‐way and probabilistic sensitivity analyses were performed to vary the assumptions across a range of plausible values.Main outcome measuresThe primary outcome was the incremental cost‐effectiveness ratio (ICER).ResultsPegylated liposomal doxorubicin (PLD) was the least costly strategy, at $55,732, followed by dostarlimab ($151,533) and pembrolizumab ($154,597). Based on a willingness‐to‐pay threshold of $100,000/QALY, PLD was cost‐effective compared with dostarlimab, with an ICER of $331,913 per QALY gained for dostarlimab, whereas pembrolizumab was ruled out by extended dominance (less effective, more costly), compared with dostarlimab. In one‐way sensitivity analyses, dostarlimab was cost‐effective when its cost was reduced to $4905 (52% reduction). These results were robust in a variety of sensitivity analyses.ConclusionsDostarlimab is associated with greater survival compared with other treatments for women with recurrent dMMR endometrial cancer. Although the agent is substantially more costly, dostarlimab became cost‐effective when its cost was reduced to $5489 per cycle.

Ovarian conservation for grade 2–3 endometrial cancer in premenopausal patients: should they stay or should they go?

Uptake and outcomes of sentinel lymph node mapping in women undergoing minimally invasive surgery for endometrial cancer

AbstractObjectiveTo examine the patterns and outcomes of sentinel lymph node (SLN) assessment in women with endometrial cancer.DesignRetrospective cohort study.SettingUnited States inpatient and outpatient hospital services.PopulationWomen with endometrial cancer who underwent a laparoscopic or robotic‐assisted hysterectomy.MethodsThe Perspective Database from 2012 to 2018 was used. Performance of lymph node dissection was classified as SLN mapping, lymph node dissection or no nodal evaluation. Adjusted regression models were developed to examine the association between SLN mapping and morbidity and cost.Main Outcome MeasuresUtilisation rates, morbidity and cost of both lymph node dissection and SLN mapping.ResultsAmong 45 381 patients, SLN mapping was performed for 7768 patients (17.1%), lymph node dissection was performed for 23 214 patients (51.2%) and no lymphatic evaluation was performed for 14 399 patients (31.7%). SLN mapping increased from 1.8% in 2012 to 35.3% in 2018, whereas the rate of lymph node dissection decreased from 63.5% to 39.1% (p &lt; 0.001). Among women who underwent nodal evaluation, residence in the west, White race and use of robotic‐assisted hysterectomy were associated with SLN mapping (p &lt; 0.05 for all). The complication rate was 5.9% for SLN mapping, compared with 7.3% in those that underwent lymph node dissection (aRR 0.85, 95% CI 0.77–0.95). The median hospital costs for women who underwent SLN mapping ($10 479) and lymph node dissection ($10 747) were higher than for those who did not undergo nodal assessment ($9149) (p &lt; 0.001).ConclusionsThe performance of SLN mapping is increasing for endometrial cancer. Compared with lymph node dissection, SLN mapping is associated with lower morbidity. SLN mapping significantly increases the costs compared with hysterectomy alone.Tweetable AbstractSLN mapping is increasing rapidly for endometrial cancer and is associated with decreased perioperative morbidity.

Trends in uterine cancer incidence and mortality: insights from a natural history model

Abstract Background Uterine cancer incidence and mortality are increasing, with concomitant disparities in outcomes between racial groups. Natural history modeling can evaluate risk factors, predict future trends, and simulate approaches to reducing mortality and disparities. Methods We designed a natural history model of uterine cancer using a multistage clonal expansion design. The model is informed by National Health and Nutrition Examination Survey, National Health Examination Survey, age, time period, birth cohort, and birth certificate data on reproductive histories and body mass index (BMI). We fit and calibrated the model to Surveillance, Epidemiology, and End Results data by race and ethnicity as well as histologic subgroup. We projected future incidence and estimated the degree of contribution of BMI, reproductive history, and competing hysterectomy to excess uterine cancer incidence. Results The model accurately replicated Surveillance, Epidemiology, and End Results incidence for endometrioid, nonendometrioid, and sarcoma subgroups for non-Hispanic Black and non-Hispanic White patients. For endometrioid, nonendometrioid, and sarcomas, BMI-attributable risks are greater for non-Hispanic White than for non-Hispanic Black patients; reproductive history–attributable risks are greater for non-Hispanic Black patients. Between 2018 and 2050, endometrioid incidence is projected to rise by 64.9% in non-Hispanic Black individuals and17.5% in non-Hispanic White individuals; the projected rise for the nonendometrioid subgroup is 41.4% in non-Hispanic Black individuals and 22.5% in non-Hispanic White individuals; the sarcoma incidence projected increase is 36% in non-Hispanic Black individuals and 29.2% in non-Hispanic White individuals. Conclusions Uterine cancer risk is substantially explained by reproductive history and BMI, with differences observed between non-Hispanic Black and non-Hispanic White individuals and future projections indicating perpetuation of disparities. Lower rates of hysterectomy and rising obesity rates will likely contribute to continued increases in uterine cancer incidence.

Patterns of pembrolizumab use for recurrent cervical cancer

This study aimed to examine the real-world use of pembrolizumab for recurrent cervical cancer as part of first-line or recurrence treatment, and its associated health care utilization. The Merative MarketScan Research Databases were used to identify newly diagnosed patients with cervical cancer who underwent primary hysterectomy or radiation from 2017 to 2022. Systemic therapy utilization, including pembrolizumab, was assessed at first recurrence. Health care utilization (hospitalization, emergency department visits, and costs) during first-line treatments for recurrence was described for patients treated with and without pembrolizumab. Multivariable regression models explored factors associated with pembrolizumab adoption and differences in health care utilization. A total of 2727 patients were identified, including 1259 (46.2%) who underwent primary hysterectomy and 1468 (53.8%) who received primary radiotherapy. Chemotherapy for recurrence was initiated in 339 patients (12.4%). Recurrence treatment was noted in 9.7% of patients initially treated with hysterectomy and in 14.8% of those receiving primary radiotherapy. Among patients treated for recurrence, 24.8% received platinum alone, 52.5% a platinum-based combination therapy, and 22.7% non-platinum regimens. Forty-one patients (12.1%) received pembrolizumab. The median duration of first-line chemotherapy for recurrence was 2.3 months (interquartile range; 1.0-5.8) overall, and 4.3 months (interquartile range; 2.4-9.8) for patients treated with pembrolizumab. Pembrolizumab utilization was associated with more recent years of recurrence, advanced age, and prior chemotherapy. While pembrolizumab use was not associated with increased inpatient stays or emergency department visits, it was associated with significantly higher total costs and chemotherapy-related expenses. Platinum-based chemotherapy is the predominant treatment for recurrent cervical cancer. Pembrolizumab utilization, although increasing, remains limited, highlighting a significant opportunity to optimize guideline-recommended therapies with proven efficacy in clinical trials.

Patterns of use of primary and first-line chemotherapy for recurrence among patients with cervical cancer

Little is known about real-world patterns of chemotherapy use in patients with cervical cancer. To examine the patterns of chemotherapy use in patients with cervical cancer METHODS: We identified patients with cervical cancer in the IBM MarketScan Database who underwent primary hysterectomy or radiation therapy between 2011 and 2020 and described their treatment in the primary setting and at first recurrence. We identified 5390 patients: 2667 (49.5%) underwent primary hysterectomy and 2723 (50.5%) primary radiotherapy. Among patients who underwent primary hysterectomy, 979 (36.7%) received adjuvant radiation, and 617 (23.1%) received primary chemotherapy. The most common chemotherapy regimens were single-agent platinum (51.7%), platinum combination therapy (42.9%), and non-platinum (3.4%). Among patients treated with primary radiation, 73.6% received primary/concurrent chemotherapy, either platinum alone (66.4% of those who received chemotherapy), platinum combinations (32.2%), or non-platinum (1.4%). The median duration of primary chemotherapy was 1.2 months. Therapy for recurrent cervical cancer was initiated in 959 patients. The most common regimens were platinum combination (63.9%), non-platinum cytotoxic agents (16.5%), single-agent platinum (14.9%), targeted therapy with bevacizumab (6.0%), and immunotherapy with pembrolizumab (3.2%). Overall, the proportion of patients treated with single-agent platinum therapy increased from 17.4% in 2011 to 32.1% in 2019, while platinum combinations decreased from 64.1% to 41.5% over the same years. Use of non-platinum agents increased from 18.5% in 2011 to 32.9% in 2018 and 26.4% in 2019. Platinum-based chemotherapy is the most commonly used therapy in patients with cervical cancer in the primary setting and at the time of recurrence. The rate of use of non-platinum agents at first recurrence has increased over time.

Minimally invasive surgery for suspected early‐stage ovarian cancer; a cost‐effectiveness study

ObjectiveWhile there are a number of benefits to minimally invasive surgery (MIS) for women with ovarian cysts, there is an increased risk of ovarian capsule rupture during the procedure, which could potentially seed the abdominal cavity with malignant cells. We developed a decision model to compare the risks, benefits, effectiveness and cost of MIS versus laparotomy in women with ovarian masses.DesignCost‐effectiveness studyPopulationHypothetical cohort of 10 000 women with ovarian masses who were undergoing surgical management.MethodsThe initial decision point in the model was performance of surgery via laparotomy or a MIS approach. Model probabilities, costs and utility values were derived from published literature and administrative data sources. Extensive sensitivity analyses were conducted to assess the robustness of the findings.Main outcome measuresThe primary outcome was the cost‐effectiveness of MIS versus laparotomy for women with a pelvic mass measured by incremental cost‐effectiveness ratios (ICERs).ResultsMIS was the least costly strategy at $7,732 per women on average, compared with $17,899 for laparotomy. In our hypothetical cohort of 10 000 women, there were 64 cases of ovarian rupture in the MIS group and 53 in the laparotomy group, while there were 26 cancer‐related deaths in the MIS group and 25 in the laparotomy group. MIS was more effective than laparotomy (188 462 QALYs for MIS versus 187 631 quality adjusted life years [QALYs] for laparotomy). Thus, MIS was a dominant strategy, being both less costly and more effective than laparotomy. These results were robust in a variety of sensitivity analyses.ConclusionMIS constitutes a cost‐effective management strategy for women with suspicious ovarian masses.Tweetable abstractMIS is a cost‐effective management strategy for women with suspicious ovarian masses.

Lessons from the Failure to Complete a Trial of Denosumab in Women With a Pathogenic BRCA1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy

Abstract Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes.

Patterns of use and outcomes of adjuvant bevacizumab therapy prior to regulatory approval in women with newly diagnosed ovarian cancer

We used real-world claims data to assess the utility of the relatively novel therapeutic bevacizumab in patients with newly diagnosed ovarian cancer in the United States after release of clinical data but prior to FDA approval. We used the IQVIA Pharmetrics Plus commercial claims database to identify women with a new diagnosis of ovarian cancer who underwent primary surgery or neoadjuvant chemotherapy followed by interval surgery from 2006 to 2018. We calculated the rate of use of bevacizumab, and the relative frequency of hospital and emergency department (ED) admissions. Treatment-related toxicities, and time to second line chemotherapy were calculated. Among 8923 women who met study parameters, 533 (6.0%) received bevacizumab. The rate of use increased over time from 1.5% in 2006 to 7.0% in 2017 (P < 0.001), with a peak of 8.6% in 2011. The use was lowest in those ≥ 70 years old (2.8%), and in the West (4.5%), and was unaffected by number of comorbidities. Over one third (35.1%) received bevacizumab for less than 3 months, and 15.9% remained on it for greater than 13 months. Bevacizumab use was not associated with hospitalization or ED admission. Toxicities included hypertension (15.0%), kidney damage (6.8%), bleeding (3.8%), venous thrombo-embolism (2.3%) and fistula (1.1%). Time from initiation of first line chemotherapy to initiation of second line therapy was 19.9 months without bevacizumab and 22.6 months with bevacizumab use. Real-world patterns of upfront bevacizumab use prior to FDA approval in 2018 differed significantly from trial data.

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.

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

Patterns of cervical cancer screening among Medicaid beneficiaries

AbstractObjectiveCervical cancer screening guidelines have evolved over time with the incorporation of human papillomavirus (HPV) testing along with cytology. Current screening guidelines recommend cytological screening every 3 years or HPV testing with or without cytology every 5 years in women age 30–65 years. We examined the use of cervical cancer screening among average‐risk Medicaid beneficiaries.DesignRetrospective cohort study.PopulationWomen age 30–64 years at average risk for cervical cancer who underwent cervical cancer screening with cytology, co‐testing or primary HPV testing from 2013 to 2016.MethodsThe IBM Watson Health Multi‐State Medicaid MarketScan Database was used. Subsequent screening rates within 3 years of the index test were examined.Main outcome measureThe rate of repeat cervical cancer screening was analysed using a cumulative incidence function.ResultsA total of 265 083 patients were identified. Overall, 43.1% (n = 114 312) had index co‐testing, 55.2% (n = 146 309) had cytology and 1.7% (n = 4462) had primary HPV testing. The cumulative incidence of early, repeat cervical cancer screening was 3.9% at 12 months, 22.7% at 24 months and 33.3% at 36 months. During the period from 12 to 24 months after follow up, 20.9% of women underwent repeat screening while 19.4% underwent repeat screening 24–36 months after the index test. Among women who did not undergo repeat cervical cancer screening, a yearly gynaecological examination was performed in only 16 627 (10.7%) during year 2 and in 11 116 (8.8%) during year 3.ConclusionAmong average‐risk Medicaid beneficiaries, cervical cancer screening is frequently overused. Women who do not undergo cervical cancer screening are unlikely to undergo routine gynaecological examination.Tweetable AbstractAmong average‐risk Medicaid beneficiaries, cervical cancer screening is frequently overused.

The Effect of a Web-Based Cervical Cancer Survivor’s Story on Parents' Behavior and Willingness to Consider Human Papillomavirus Vaccination for Daughters: Randomized Controlled Trial

Background Providing adequate information to parents who have children eligible for human papillomavirus (HPV) vaccination is essential to overcoming vaccine hesitancy in Japan, where the government recommendation has been suspended. However, prior trials assessing the effect of brief educational tools have shown only limited effects on increasing the willingness of parents to vaccinate their daughters. Objective The aim of this trial is to assess the effect of a cervical cancer survivor’s story on the willingness of parents to get HPV vaccination for their daughters. Methods In this double-blinded, randomized controlled trial (RCT) implemented online, we enrolled 2175 participants aged 30-59 years in March 2020 via a webpage and provided them with a questionnaire related to the following aspects: awareness regarding HPV infection and HPV vaccination, and willingness for HPV vaccination. Participants were randomly assigned (1:1) to see a short film on a cervical cancer survivor or nothing, stratified by sex (male vs female) and willingness for HPV vaccination prior to randomization (yes vs no). The primary endpoint was the rate of parents who agreed for HPV vaccination for their daughters. The secondary endpoint was the rate of parents who agreed for HPV vaccination for their daughters and the HPV vaccination rate at 3 months. The risk ratio (RR) was used to assess the interventional effect. Results Of 2175 participants, 1266 (58.2%) were men and 909 (41.8%) were women. A total of 191 (8.8%) participants were willing to consider HPV vaccination prior to randomization. Only 339 (15.6%) participants were aware of the benefits of HPV vaccination. In contrast, 562 (25.8%) participants were aware of the adverse events of HPV vaccination. Although only 476 (21.9%) of the respondents displayed a willingness to vaccinate their daughters for HPV, there were 7.5% more respondents in the intervention group with this willingness immediately after watching the short film (RR 1.41, 95% CI 1.20-1.66). In a subanalysis, the willingness in males to vaccinate daughters was significantly higher in the intervention group (RR 1.50, 95% CI 1.25-1.81); however, such a difference was not observed among females (RR 1.21, 95% CI 0.88-1.66). In the follow-up survey at 3 months, 1807 (83.1%) participants responded. Of these, 149 (8.2%) responded that they had had their daughters receive vaccination during the 3 months, even though we could not see the effect of the intervention: 77 (7.9%) in the intervention group and 72 (8.7%) in the control group. Conclusions A cervical cancer survivor’s story increases immediate willingness to consider HPV vaccination, but the effect does not last for 3 months. Furthermore, this narrative approach to parents does not increase vaccination rates in children eligible for HPV vaccination. Trial Registration UMIN Clinical Trials Registry UMIN000039273; https://tinyurl.com/bdzjp4yf

Neoadjuvant Chemotherapy Versus Primary Cytoreductive Surgery for Metastatic Endometrial Cancer

ABSTRACT Objective To evaluate the pattern of use and clinical outcomes associated with neoadjuvant chemotherapy (NACT) compared with primary debulking surgery (PDS) in patients with stage IV endometrial cancer. Methods We utilized the National Cancer Database to identify individuals diagnosed with stage IV endometrial cancer, and categorized them according to receipt of NACT or PDS. Propensity score weighting using inverse probability of treatment weighting was applied. Survival outcomes were evaluated using both an intention‐to‐treat (ITT) analysis, which included all eligible patients, and a per‐protocol (PP) analysis restricted to those who underwent chemotherapy and surgery. Results Among 18,205 patients, NACT utilization rose from 30.3% in 2010 to 73.8% in 2021 ( p  &lt; 0.0001). In the multivariable analysis, patients diagnosed in more recent years, Black and Hispanic race and ethnicity, Medicaid insurance, serous histology, and greater comorbidities were associated with NACT ( p  &lt; 0.05). In the ITT analysis, there was no mortality difference within 4 months after diagnosis between NACT patients and PDS patients (aHR = 1.03; 95% CI: 0.96–1.11); however, after 4 months, patients treated with NACT experienced higher mortality than those undergoing PDS (aHR = 1.58; 95% CI: 1.51–1.64). In the PP analysis, NACT patients had lower mortality compared to PDS patients within 24 months after diagnosis (aHR = 0.93; 95% CI, 0.88–0.99) but a 34% higher mortality after 24 months (aHR = 1.34; 95% CI, 1.23–1.47). Conclusion Utilization of NACT has expanded among patients with metastatic endometrial cancer. Primary debulking surgery with postoperative chemotherapy is linked to higher early mortality but improved long‐term outcomes relative to treatment strategies beginning with NACT followed by surgery.

Use and outcomes of hormonal therapy for advanced-stage, low-grade serous ovarian cancer.

To examine trends in the use of hormonal therapy for advanced-stage, low-grade serous ovarian carcinoma and to compare survival outcomes of patients who received traditional chemotherapy, hormonal therapy alone, or the combination of both. Women with stage II to IV low-grade serous ovarian cancer diagnosed between 2011 and 2020 were identified from the National Cancer Data Base. Patients undergoing primary surgery followed by adjuvant chemotherapy, hormonal therapy, or both were included. A multinomial logistic regression model was used to examine factors associated with treatment. Propensity score-weighted Cox proportional hazards models (via inverse probability of treatment weighting) were applied to compare overall survival across the treatment groups. Among 1532 women, 68.0% received chemotherapy alone, 12.3% received hormonal therapy alone, and 19.8% received combination therapy. Use of hormonal monotherapy increased from 0.8% in 2011 to 27.4% in 2020, and use of combination therapy increased from 0.8% to 32.6% (p 70 years) (p = .001) and those with Medicare insurance (p < .001), while combination therapy was more common in women with stage III to IV disease (p = .001). After applying propensity score weighing, 5-year survival was 76.6% (95% CI 73.2% to 79.7%) for chemotherapy alone, 85.5% (95% CI 66.1% to 94.3%) for hormonal therapy alone, and 75.8% (95% CI 59.7% to 86.2%) for combination therapy. Compared to chemotherapy alone, the HR for all-cause mortality was 0.74 (95% CI 0.46 to 1.19) for hormonal therapy alone and 0.88 (95% CI 0.63 to 1.24) for combination therapy. In advanced-stage low-grade serous ovarian cancer, the use of hormonal therapy increased substantially over time. Comparable survival outcomes across modalities suggest hormonal therapy may be a viable treatment option, particularly for patients who will not tolerate the side effects of cytotoxic chemotherapy.

Projected Trends in the Incidence and Mortality of Uterine Cancer in the United States

Abstract Background: To develop a natural history model for uterine cancer calibrated to population-based incidence and mortality data to project future trends in the disease through 2050. Methods: We developed a state-transition microsimulation model of uterine cancer. The model begins at 18 years of age and simulates Black and White patients, includes transition states for precursor lesions, and separately models endometrioid and nonendometrioid tumors. The model was calibrated to population-based incidence and mortality data using parameter extrapolation. Results: The model closely fit population-based incidence and mortality data of uterine cancer. From 2020 to 2050, the incidence of uterine cancer is projected to increase in White women to 74.2 cases per 100,000 (compared with 57.7 cases per 100,000 in 2018) and increase to 86.9 per 100,000 (compared with 56.8 cases per 100,000 in 2018) in Black women. Among White women, incidence-based mortality will increase from 6.1 per 100,000 in 2018 to 11.2 per 100,000 in 2050, whereas incidence-based mortality in Black women will increase from 14.1 per 100,000 to 27.9 per 100,000. Endometrioid tumors are expected to increase considerably in both White and Black women; White women will experience only a slight increase in nonendometrioid tumors, whereas the incidence of these tumors will increase substantially in Black women. Conclusions: The incidence and mortality of uterine cancer are projected to increase substantially over the next three decades. Black women will experience a disproportionate increase in the disease. Impact: Projecting the incidence and mortality of uterine cancer can facilitate future cancer control efforts.

Association of sentinel lymph node biopsy and isolated tumor cells in cervical cancer.

This retrospective cohort study examined 4991 patients with the American Joint Commission on Cancer T1-2 classification who underwent primary anti-cancer surgery, including lymph node evaluation (sentinel lymph node biopsy n = 976, and lymphadenectomy n = 4015), identified in the National Cancer Database from 2018 to 2022. In propensity score inverse probability of treatment weighting, the sentinel lymph node biopsy group had a 2-fold higher rate of low-volume metastasis (isolated tumor cells or micro-metastasis) than the lymphadenectomy group (2.7% vs 1.3%, OR 2.03, 95% CI 1.26 to 3.27). When the low-volume metastasis was further stratified, sentinel lymph node biopsy was associated with increased odds of isolated tumor cells (OR 2.33, 95% CI 1.30 to 4.17) compared with micro-metastasis (OR 1.58, 95% CI 0.70 to 3.57). This association was consistent in the Surveillance, Epidemiology, and End Results Program data from 2018 to 2022 (n = 2973), and sentinel lymph node biopsy was associated with increased odds of isolated tumor cells (OR 3.31, 95% CI 1.65 to 6.64) compared with micro-metastasis (OR 1.12, 95% CI 0.58 to 2.16) compared with lymphadenectomy. In conclusion, these data suggest that sentinel lymph node mapping and biopsy with ultra-staging can identify more isolated tumor cells in cervical cancer.

Comparison of Two-Position and Four-Position Cervical Injection Techniques for Sentinel Lymph Node Mapping in Endometrial Cancer Using Methylene Blue

This clinical trial evaluates lymph node mapping in newly diagnosed endometrial cancer patients undergoing surgery. The standard technique uses a 2-point methylene blue cervical injection. The study aims to determine if increasing injection points improves mapping success.