Koji Matsuo

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.

Correspondence on “Sentinel lymph node assessment in patients with atypical endometrial hyperplasia: a systematic review and meta-analysis” by Vieira-Serna et al

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.

Intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer: association for pathological factors and oncologic outcomes

To examine the association between intrauterine manipulator use and pathological factors and oncologic outcomes in patients with endometrial cancer who had laparoscopic hysterectomy in Japan. This was a nationwide retrospective cohort study of the tumor registry of the Japan Society of Obstetrics and Gynecology. Study population was 3846 patients who had laparoscopic hysterectomy for endometrial cancer from January 2015 to December 2017. An automated 1-to-1 propensity score matching with preoperative and intraoperative demographics was performed to assess postoperative pathological factors associated with the intrauterine manipulator. Survival outcomes were assessed by accounting for possible pathological mediators related to intrauterine manipulator use. Most patients had preoperative stage I disease (96.5%) and grade 1-2 endometrioid tumors (81.9%). During the study period, 1607 (41.8%) patients had intrauterine manipulator use and 2239 (58.2%) patients did not. In the matched cohort, the incidences of lymphovascular space invasion in the hysterectomy specimen were 17.8% in the intrauterine manipulator group and 13.3% in the non-manipulator group. Intrauterine manipulator use was associated with a 35% increased odds of lymphovascular space invasion (adjusted odds ratio 1.35, 95% confidence interval (CI) 1.08 to 1.69). The incidences of malignant cells identified in the pelvic peritoneal cytologic sample at hysterectomy were 10.8% for the intrauterine manipulator group and 6.4% for the non-manipulator group. Intrauterine manipulator use was associated with a 77% increased odds of malignant peritoneal cytology (adjusted odds ratio 1.77, 95% Cl 1.29 to 2.31). The 5 year overall survival rates were 94.2% for the intrauterine manipulator group and 96.6% for the non-manipulator group (hazard ratio (HR) 1.64, 95% Cl 1.12 to 2.39). Possible pathological mediators accounted HR was 1.36 (95%Cl 0.93 to 2.00). This nationwide analysis of predominantly early stage, low-grade endometrial cancer in Japan suggested that intrauterine manipulator use during laparoscopic hysterectomy for endometrial cancer may be associated with an increased risk of lymphovascular space invasion and malignant peritoneal cytology. Possible mediator effects of intrauterine manipulator use on survival warrant further investigation, especially with a prospective setting.

Lymph node evaluation for endometrial hyperplasia: a nationwide analysis of minimally invasive hysterectomy in the ambulatory setting

Abstract Background Given the possibility of occult endometrial cancer where nodal status confers important prognostic and therapeutic data, role of lymph node evaluation at hysterectomy for endometrial hyperplasia is currently under active investigation. The objective of the current study was to examine the characteristics related to lymph node evaluation at the time of minimally invasive hysterectomy when performed for endometrial hyperplasia in an ambulatory surgery setting. Methods The Healthcare Cost and Utilization Project's Nationwide Ambulatory Surgery Sample was retrospectively queried to examine 49,698 patients with endometrial hyperplasia who underwent minimally invasive hysterectomy from 1/2016 to 12/2019. A multivariable binary logistic regression model was fitted to assess the characteristics related to lymph node evaluation at hysterectomy and a classification tree model with recursive partitioning analysis was constructed to examine the utilization pattern of lymph node evaluation. Results Lymph node evaluation was performed in 2847 (5.7%) patients. In a multivariable analysis, (i) patient factors with older age, obesity, high census-level household income, and large fringe metropolitan, (ii) surgical factors with total laparoscopic hysterectomy and recent year surgery, (iii) hospital parameters with large bed capacity, urban setting, and Western U.S. region, and (iv) histology factor with presence of atypia were independently associated with increased utilization of lymph node evaluation at hysterectomy (all, P  &lt; 0.05). Among those independent factors, presence of atypia exhibited the largest association for lymph node evaluation (adjusted odds ratio 3.75, 95% confidence interval 3.39–4.16). There were 20 unique patterns of lymph node evaluation based on histology, hysterectomy type, patient age, year of surgery, and hospital bed capacity, ranging from 0 to 20.3% (absolute rate difference, 20.3%). Conclusion Lymph node evaluation at the time of minimally invasive hysterectomy for endometrial hyperplasia in the ambulatory surgery setting appears to be evolving with large variability based on histology type, hysterectomy modality, patient factors, and hospital parameters, warranting a consideration of developing clinical practice guidelines.

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 potential role of GLP-1 receptor agonist targeting in fertility-sparing treatment in obese patients with endometrial malignant pathology: a call for research

Most patients diagnosed with endometrial hyperplasia or cancer are obese. Obesity, along with polycystic ovarian syndrome (PCOS) and type-2 diabetes mellitus (T2DM), may act synergistically to increase risk of malignant endometrial pathology. Incidence of malignant endometrial pathology is increasing, particularly in reproductive aged women. In patients who desire future fertility, the levonorgestrel intrauterine device (LNG-IUD) is often utilized. If the first-line progestin therapy fails, there is not an effective second-line adjunct option. Moreover, pregnancy rates following fertility-sparing treatment are lower-than-expected in these patients. This clinical opinion provides a summary of recent studies exploring risk factors for the development of malignant endometrial pathology including obesity, PCOS, and T2DM. Studies assessing efficacy of fertility-sparing treatment of malignant endometrial pathology are reviewed, and a potential new adjunct treatment approach to LNG-IUD is explored. There is an unmet-need for a personalized treatment approach in cases of first-line progestin treatment failure. Glucagon-like peptide 1 receptor agonists are a class of anti-diabetic agents, but may have a role in fertility-sparing treatment of obese patients with malignant endometrial pathology by reducing weight, decreasing inflammation, and decreasing insulin resistance; these changes may also improve chances of subsequent pregnancy. This hypothesis warrants further exploration.

Trend and characteristics of minimally invasive surgery for patients with endometrial cancer in Japan

Owing to the potential benefits of minimally invasive hysterectomy for endometrial cancer, the practice pattern has recently shifted in Japan. This study examined the trends in minimally invasive surgery (MIS) in patients with endometrial cancer in Japan. This retrospective observational study examined the Japan Society of Obstetrics and Gynecology Tumor Registry database between 2015-2019. This study examined the time-specific proportion change and predictors of MIS use in initial endometrial cancer treatment in Japan, and compared it with the use of abdominal surgery. Additionally, the association between hospital surgical treatment volume and MIS use was examined. A total of 14,059 patients (26.5%) underwent minimally invasive hysterectomy, and 39,070 patients (73.5%) underwent abdominal hysterectomy in the study period. Patients who underwent MIS were more likely to be treated at high-volume centers, younger, central, or western Japan residents, registered in recent years, and had a tumor with stage I disease, type 1 histology, and less myometrial invasion (all adjusted p<0.05). The proportion of MIS treatments increased from 19.1% in 2015 to 34.3% in 2019 (p<0.001). On multivariable analysis, treatment at high-volume centers was a contributing factor for MIS (adjusted odds ratio=3.85; 95% confidence interval=3.44-4.30). MIS at high-volume centers increased significantly from 24.8% to 41.0% (p<0.001) during the study period, whereas MIS at low-volume centers remained at median 8.8%. MIS has increased significantly in recent years, accounting for nearly 34% of surgical management of endometrial cancer in Japan. High-volume treatment centers take the lead in performing MIS.

Cancer Stage-Shifting with Sentinel Lymph Node Biopsy in Low-Grade Endometrial Cancer

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

Malignant peritoneal cytology in endometrial cancer: a contemporary review

In endometrial cancer, malignant peritoneal cytology (MPC) refers to the presence of tumor cells in the peritoneal cytologic specimen obtained at hysterectomy. MPC was once a component of uterine cancer staging criteria, but it is no longer included in the current revision. Multiple societies and organizations, however, continue to recommend peritoneal cytologic testing at the time of hysterectomy for endometrial cancer. This contemporary review provides a clinical summary of recent studies evaluating MPC, including risk factors and prognosis. Compared to prior studies showing a lack of impact on oncologic outcome, recent studies have larger sample sizes, use stricter inclusion criteria, and perform histology/cancer stage-specific analyses to balance risk factors and provide explicit interpretations for oncologic outcomes related to MPC. These newer data provide evidence that MPC does have a prognostic impact. Three key domains related to MPC are followings: First, recognition of MPC as a prognostic factor for endometrial cancer irrespective to stage (early and advanced) and histology (endometrioid and non-endometrioid) is necessary. Second, peritoneal cytologic testing at the beginning of each staging surgery is recommended. Last, incorporation of peritoneal cytology status in adjuvant treatment algorithms is useful and merits further development.

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.

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

Effects of aspirin and statin use on venous thromboembolism prophylaxis and survival in patients with endometrial cancer

Acetylsalicylic acid (aspirin) and statins are commonly used to manage and prevent cardiovascular diseases. Recent studies have suggested the benefits of aspirin or statin use in venous thromboembolism (VTE) prophylaxis and survival outcome improvement in women with endometrial cancer. In this study, we reviewed the effects of aspirin or statin use on VTE prophylaxis and survival outcome in women with endometrial cancer. Among women with endometrial cancer, aspirin use exerted a modest effect on VTE prophylaxis, whereas statin use was associated with a decreased prevalence of VTE, especially in women with obesity and type II cancer, compared with those in non-users. Aspirin use improved cause-specific survival in women with endometrial cancer, aged less than 60 years, who were obese and presented with type I cancer. Statin use was associated with better cause-specific survival in women with type II cancer. The combination of aspirin and statins may be the most effective strategy in improving on VTE prophylaxis and survival outcomes in obese women with type II cancer. Targeting of the appropriate population with endometrial cancer may enhance the efficacy of aspirin or statins on VTE prophylaxis and survival outcomes in women with endometrial cancer.

Predictors of subsequent pregnancy following medical treatment in obese women with complex atypical hyperplasia

Clinico‐pathological significance of suspicious peritoneal cytology in endometrial cancer

AbstractBackground and ObjectivesSuspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer.MethodsA population‐based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I–III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine‐Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology.ResultsSuspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution‐hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29–2.20, p &lt; 0.001) and all‐cause mortality (adjusted‐HR: 1.55, 95% CI: 1.27–1.90, p &lt; 0.001) compared with negative peritoneal cytology. Sensitivity analysis demonstrated that suspicious peritoneal cytology had discrete overall survival improvement compared with malignant peritoneal cytology in a propensity score weighting model (HR: 0.85, 95% CI: 0.72–0.99, p = 0.049).ConclusionOur study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer.

ASO Author Reflections: Malignant Peritoneal Cytology, Adjuvant Therapy Choice, and Survival in Advanced Endometrial Cancer

Association Between Adjuvant Therapy and Survival in Stage II–III Endometrial Cancer: Influence of Malignant Peritoneal Cytology

The aim of this study was to examine the survival effect of adjuvant therapy in stage II-III endometrial cancer based on peritoneal cytology results. The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II-III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results. Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p < 0.05). In a propensity score-weighted model, malignant peritoneal cytology was associated with increased all-cause mortality compared with negative peritoneal cytology (hazard ratio 1.35, 95% confidence interval 1.23-1.48). Adjuvant therapy types varied based on histology and peritoneal cytology results. In non-endometrioid histology, the combination of chemotherapy and whole pelvic radiotherapy (WPRT) was associated with improved overall survival compared with chemotherapy or WPRT alone irrespective of the peritoneal cytology results (p < 0.05). The combination of chemotherapy and WPRT was also associated with improved overall survival in women with endometrioid histology and malignant peritoneal cytology (p = 0.026). Women with endometrioid histology and negative peritoneal cytology represented the most common subpopulation (46.5%), and overall survival was similar regardless of which of the three adjuvant therapy modalities was used (p = 0.319). Malignant peritoneal cytology is prevalent and prognostic in stage II-III endometrial cancer. This study found that the surgeon's choice and benefit of adjuvant therapy for women with stage II-III endometrial cancer differed depending on the status of peritoneal cytology.

Malignant peritoneal cytology in endometrial cancer: Areas of unmet need for evidence

Malignant peritoneal cytology and decreased survival of women with stage I endometrioid endometrial cancer

To examine the association between malignant peritoneal cytology and survival in women with early-stage endometrioid endometrial cancer. This is a retrospective cohort study using the Surveillance, Epidemiology, and End Results Program from 2010 to 2016. Women with stage I endometrioid endometrial cancer who had peritoneal cytology testing at hysterectomy were examined (N = 24,800). Characteristics and survival related to malignant peritoneal cytology were assessed. The propensity score inverse probability of treatment weighting was used to balance the measured covariates. Malignant peritoneal cytology was reported in 1081 (4.4%) women. In multivariable analysis, stage IB disease and moderately/poorly differentiated tumours were associated with an increased likelihood of malignant peritoneal cytology (both P < 0.05). In a weighted model, malignant peritoneal cytology was associated with decreased cause-specific survival (5-year rates, 92.1% versus 96.8%, hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.56-2.52) and overall survival (89.4% versus 93.1%, HR 1.41, 95% CI 1.16-1.72). In sensitivity analyses, malignant peritoneal cytology was associated with decreased overall survival in the high-intermediate-risk group (5-year rates, 77.8% versus 83.6%, HR 1.57, 95% CI 1.20-2.06) and decreased cause-specific survival in the low-risk group (95.4% versus 98.0%, HR 1.64, 95% CI 1.01-2.68). In the high-intermediate-risk group with malignant peritoneal cytology, postoperative chemotherapy was associated with improved overall survival compared to whole pelvic radiotherapy (5-year rates, 82.7% versus 64.6%, HR 0.36, 95% CI 0.14-0.96). This association was not observed in negative cytology cases (81.5% versus 79.7%, HR 0.78, 95% CI 0.53-1.14). Malignant peritoneal cytology may be associated with decreased survival in stage I endometrioid endometrial cancer.

Route-specific association of progestin therapy and concurrent metformin use in obese women with complex atypical hyperplasia

Previous studies have suggested that metformin use may enhance the therapeutic effect of progestin therapy for endometrial hyperplasia or malignancy. However, it is not known how the impact of concurrent metformin may be altered by route of progestin therapy, either locally via an intrauterine device or systemically. This study examined the effectiveness of concurrent metformin use and progestin therapy for women with complex atypical hyperplasia stratified by progestin route (systemic vs local). This single-institution retrospective study examined consecutive women with complex atypical hyperplasia who received progestin therapy from 2003 to 2018. Time-dependent analyses for complete response rate were performed comparing concurrent metformin users versus non-users in the oral progestin group and in the levonorgestrel-releasing intrauterine device group. Across the study cohort (n=245), there were 137 (55.9%) women who responded to progestin therapy. In the oral progestin group (n=176), the median age and body mass index were 36 years and 37.7 kg/m In a predominantly obese population, concurrent metformin may possibly offer treatment benefit when used with the levonorgestrel-releasing intrauterine device.

A cesarean delivery sequela:

Comparing Durvalumab, Olaparib, and Cediranib Monotherapy, Combination Therapy, or Chemotherapy in Patients with Platinum-Resistant Ovarian Cancer with Prior Bevacizumab: The Phase II NRG-GY023 Trial

Abstract Purpose: We assessed the efficacy of anti–PD-L1 durvalumab in combination with olaparib and cediranib (DOC), compared with the standard-of-care chemotherapy (SOC) in patients with platinum-resistant ovarian cancer (PROC), who had prior bevacizumab. Patients and Methods: NRG-GY023 was the first randomized four-arm superiority phase II trial enrolling patients with high-grade serous/endometrioid or clear-cell PROC with prior bevacizumab exposure. Patients were randomized 1:2:2:2 to SOC (weekly paclitaxel, topotecan, or pegylated liposomal doxorubicin), DOC, durvalumab + cediranib (DC), or olaparib + cediranib (OC). The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival, overall response rate, and safety. The design had 80% power to detect an HR of 0.5 using a one-sided, α = 0.1-level test for each comparison with the SOC with a preplanned interim analysis. Experimental arms with HR estimates (vs. SOC) &amp;gt;0.87 could be discontinued. Results: A total of 153 patients were enrolled between April 4, 2021, and February 1, 2023. Accrual was permanently closed on February 1, 2023, due to futility. With a data cutoff of September 9, 2024, the median PFS was 3.4, 2.9, 2.5, and 2.8 months, and median overall survival was 7.5, 8.3, 5.7, and 10.2 months for SOC, DOC, DC, and OC, respectively. The overall response rate was 4.3% [95% confidence interval (CI), 0.00–0.19], 15.9% (95% CI, 0.07–0.29), 11.9% (95% CI, 0.05–0.24), and 9.1% (95% CI, 0.03–0.20) for SOC, DOC, DC, and OC, respectively. Compared with SOC, the PFS HR estimates were 1.003 (95% CI, 0.56–1.80), 1.108 (95% CI, 0.63–1.96), and 1.021 (95% CI, 0.57–1.82) for DOC, DC, and OC, respectively. No new safety signals were observed. Conclusions: In patients with PROC with prior bevacizumab, all experimental arms failed to reach the primary objective of improving PFS compared with SOC.

Salvage hysterectomy for persistent residual cervical cancer: assessment of prognostic factors

In this multicenter retrospective cohort study of 99 patients who underwent salvage hysterectomy for residual disease in the uterine cervix following the completion of definitive radiotherapy for cervical cancer across 25 Japan Clinical Oncology Group-affiliated centers from 2005-2014, (i) time duration from the completion of definitive radiotherapy to the diagnosis of residual disease in the uterine cervix, (ii) salvage hysterectomy surgical margin status, and (iii) extent of residual disease, were independently associated with progression-free survival (PFS). Specifically, (i) time duration to identify residual disease of >62 days was associated with decreased PFS compared to ≤62 days (4-year rates 21.8% vs. 55.0%, adjusted-hazard ratio [aHR]=2.69, 95% confidence interval [CI]=1.55-4.67); (ii) presence of tumor in the surgical margin of hysterectomy specimen was associated with 4 times increased risk of disease progression compared to tumor-free surgical margin (4-year PFS rates 0% vs. 45.3%, aHR=4.27, 95% CI=2.20-8.29); and (iii) hazards of disease progression was 4.5-fold increased when the residual disease extended beyond the uterine cervix compared to residual disease within the uterine cervix only (4-year PFS rates 11.1% vs. 50.6%, aHR=4.54, 95% CI=2.60-7.95). In the absence of these 3 prognostic factors, 4-year PFS rate reached nearly 80% (78.6%, SAL-HYS criteria). In sum, these data suggested that early detection of persistent, residual disease following definitive radiotherapy for cervical cancer may be the key to improve survival if salvage hysterectomy is considered as a tailored treatment option. Ideal surgical candidate would be uterine cervix-contained disease and assurance of adequate tumor-free surgical margin.

Assessment of postoperative therapy de-escalation for early-stage, intermediate-risk cervical cancer

The objective of this study was to assess the oncologic outcome of surgically-treated patients with early-stage, intermediate-risk cervical cancer according to postoperative therapy modality. This retrospective cohort study queried the Japanese Gynecologic Oncology Group's nationwide surgical data platform. The study population was 1084 patients with stage IB cervical cancer who underwent primary radical hysterectomy and lymphadenectomy from 2004 to 2008. Histology type-incorporated intermediate-risk factor patterns were clustered into three groups based on recurrence risk. Oncologic outcomes were assessed per postoperative therapy: external beam radiotherapy alone, concurrent chemo-radiotherapy, chemotherapy alone, and no treatment. Histology-incorporated intermediate-risk groups included: no lympho-vascular space invasion in any histology, or squamous cell carcinoma with lympho-vascular space invasion but no deep stromal invasion (n=559, 51.6%, group 1); squamous cell carcinoma with both lympho-vascular space invasion and deep cervical stromal invasion (n=281, 25.9%; group 2); and non-squamous histology with lympho-vascular space invasion (n=244, 22.5%; group 3). The 5-year disease-free survival rates were 93.3%, 89.3%, and 82.5% for group 1,-2, and -3, respectively (p0.05). In this retrospective investigation in Japan, active surveillance without postoperative therapy following radical hysterectomy and lymphadenectomy was not associated with oncologic outcome in early-stage, intermediate-risk cervical cancer.

Considerations for route of hysterectomy in low-risk cervical cancer

Intraoperative rupture and chemotherapy use in stage I ovarian cancer

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.

Significance of lymph node ratio on survival of women with borderline ovarian tumors

To assess the qualitative and quantitative measures of the effect of pelvic lymph node involvement on survival of women with borderline ovarian tumors (BOTs). This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program between 1988 and 2003. Women with stage T1-3 BOTs who had results of pelvic lymph node status at surgery were included. The effect of lymph node involvement on cause-specific survival (CSS) was evaluated using multivariable analysis with the following approaches: (1) any involvement, (2) involvement of multiple nodes (≥ 2 nodes), and (3) lymph node ratio (LNR), defined as the ratio of the number of tumor-containing lymph nodes to the total number of harvested lymph nodes. A total of 1524 women were examined for analysis. Median count of sampled nodes was 8 (interquartile range 3-15), and there were 81 (5.3%, 95% confidence interval [CI] 4.2-6.4) women who had lymph node involvement. Median follow-up was 15.8 (interquartile range 13.8-18.9) years, and 83 (5.4%) women died of BOTs. After controlling for age, histology, stage, and tumor size, only LNR remained an independent prognostic factor for decreased CSS (adjusted hazard ratio [HR] per percentage unit 1.015, 95% CI 1.003-1.026, P = 0.014), whereas any involvement (adjusted HR 1.700, 95% CI 0.843-3.430, P = 0.138) and involvement of multiple nodes (adjusted HR 1.644, 95% CI 0.707-3.823, P = 0.249) did not. On cutoff analysis, LNR ≥ 13% had the largest magnitude of significance on multivariable analysis of CSS (adjusted HR 2.399, 95% CI 1.163-4.947, P = 0.018). Our study suggests that high pelvic LNR may be a prognostic factor associated with decreased CSS in women with BOTs.

Temporal trends of subsequent breast cancer among women with ovarian cancer: a population-based study

To examine trends, characteristics and outcomes of women who develop both ovarian and breast cancers. This is a retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1973 to 2013. Among ovarian cancer (n = 133,149) and breast cancer (n = 1,143,219) cohorts, women with both diagnoses were identified and temporal trends, tumor characteristics and survival were examined. There were 6446 women with both malignancies, representing 4.8% of the ovarian cancer cohort and 0.6% of the breast cancer cohort. Women with ovarian cancer who had secondary breast cancer were younger than those without secondary breast cancer early in the study period (52.3 versus 59.2 in 1973) but older in more recent years (68.5 versus 62.1 in 2013, P < 0.001). The number of breast cancer survivors who developed postcedent ovarian cancer decreased from 1.5 to 0.2% from 1979 to 2008 (relative risk reduction 90.0%, P < 0.05). Similarly, the number of ovarian cancer survivors who developed postcedent breast cancer decreased from 7.2 to 2.0% from 1973 to 2008 (relative risk reduction 72.4%, P < 0.05). Tumor characteristics were more likely to be favorable in women with ovarian cancer who developed postcedent breast cancer but unfavorable in those who had antecedent breast cancer (all, P < 0.05). Women with ovarian cancer who had secondary breast cancer had superior cause-specific survival compared to those who did not develop breast cancer regardless of breast cancer timing (P < 0.05). Our study demonstrated that the demographics of women who develop breast cancer and ovarian cancer have changed over time and diagnosis of secondary breast cancer after ovarian cancer has decreased.

Diagnosis-shift between low-grade serous ovarian cancer and serous borderline ovarian tumor: A population-based study

To determine changes in the characteristics of low-grade serous ovarian cancer (LGSOC) and serous borderline ovarian tumor (serous-BOT) in a time-specific manner. We conducted a population-based retrospective study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2000. Trends, demographics, and outcomes of 775 women with well-differentiated serous ovarian cancer, used as a surrogate for LGSOC, were compared to 3937 women with serous-BOT. In the multivariable analysis, women with LGSOC were more likely to be older, have stage II-IV disease, and have undergone hysterectomy at surgery, but less likely to be a Western U.S. resident compared to those with serous-BOT (all, adjusted-P < 0.05). During the study period, the number of LGSOCs decreased by 25.9%, particularly stage I disease (37.6% relative decrease) compared to stage II-IV disease (21.1% relative decrease) (all, P < 0.05). With a median follow-up of 16.9 years, there was a decreasing trend in the 15-year overall survival rates among LGSOC (28.7% relative decrease, P = 0.056) but not in serous-BOT (2.5% relative increase, P = 0.416) as a whole cohort. The magnitude of hazard risk from all-cause death for women with LGSOC compared to those with serous-BOT increased by 68.9% from 1988 to 2000 (P < 0.001). LGSOC remained an independent prognostic factor for decreased overall survival compared to serous-BOT (adjusted-P < 0.05). Our study suggests that the decreasing number and survival of LGSOC over time may be due to a diagnosis-shift from LGSOC to serous-BOT. Given the distinct characteristics and outcomes of LGSOC compared to serous-BOT, our study endorses the importance of making the correct diagnosis upfront. Whether this diagnostic-shift supports a hypothesis that serous-BOT is a precursor lesion of LGSOC merits further investigation.

Evolving population-based statistics for rare epithelial ovarian cancers

To describe how population-based statistics for rare epithelial ovarian cancers are evolving. This is a retrospective observational study examining the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Overall survival (OS) of clear cell (OCCC), mucinous (MOC), and low-grade serous (LGSOC) ovarian cancers were compared to high-grade serous ovarian cancer (HGSOC) by fitting a propensity score matching. Among 113,365 ovarian malignancies, 5780 OCCCs (5.1%), 7561 MOCs (6.7%), and 2021 LGSOCs (1.8%) were compared to 38,199 HGSOCs. OCCCs and MOCs were more likely to be diagnosed with stage I disease compared to HGSOC (57.0-59.5% versus 8.6%, P<0.001). For early-stage disease, OCCC (hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.82-1.01) and MOC (HR 0.94, 95%CI 0.85-1.04) had similar OS to HGSOC whereas LGSOC had superior OS (HR 0.93, 95%CI 0.89-0.97) versus HGSOC. Conversely, for advanced-stage disease, OCCC (HR 1.42, 95%CI 1.32-1.53) and MOC (HR 1.11, 95%CI 1.09-1.13) had poorer OS whereas LGSOC (HR 0.86, 95%CI 0.84-0.89) had superior OS compared to HGSOC. OCCC (HR range, 1.92-2.45) and MOC (HR range, 1.73-2.22) had particularly poorer OS in the first three years following diagnosis compared to HGSOC. Population-level statistics for advanced-stage disease showed that 5-year OS rates have increased in HGSOC (16.9% to 36.8%, P<0.001) and LGSOC (50.8% to 66.4%, P=0.010); but remain unchanged for OCCC (21.0% to 28.2%, P=0.174) and MOC (21.4% to 16.5%, P=0.102). OCCC, MOC, and LGSOC comprise 2-7% of ovarian malignancies, have distinct characteristics and survival compared to HGSOC. While these rare tumors have a favorable to comparable prognosis in early-stage disease, disproportionally poor survival in advanced-stage OCCC and MOC highlights the need for further research into novel treatment strategies.

Secondary haematologic malignancies in women with ovarian cancer receiving poly-ADP ribose polymerase inhibitor therapy

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.

CD70 antibody‐drug conjugate: A potential novel therapeutic agent for ovarian cancer

AbstractThis study aimed to investigate the cytotoxicity of a cluster of differentiation 70 antibody‐drug conjugate (CD70‐ADC) against ovarian cancer in in vitro and in vivo xenograft models. CD70 expression was assessed in clinical samples by immunohistochemical analysis. Western blotting and fluorescence‐activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines A2780 and SKOV3, and in the cisplatin‐resistant ovarian cancer cell lines A2780cisR and SKOV3cisR. CD70 expression after cisplatin exposure was determined in A2780 cells transfected with mock‐ or nuclear factor (NF)‐κB‐p65‐small interfering RNA. We developed an ADC with an anti‐CD70 monoclonal antibody linked to monomethyl auristatin F and investigated its cytotoxic effect. We examined 63 ovarian cancer clinical samples; 43 (68.3%) of them expressed CD70. Among patients with advanced stage disease (n = 50), those who received neoadjuvant chemotherapy were more likely to exhibit high CD70 expression compared to those who did not (55.6% [15/27] vs 17.4% [4/23], P &lt; .01). CD70 expression was confirmed in A2780cisR, SKOV3, and SKOV3cisR cells. Notably, CD70 expression was induced after cisplatin treatment in A2780 mock cells but not in A2780‐NF‐κB‐p65‐silenced cells. CD70‐ADC was cytotoxic to A2780cisR, SKOV3, and SKOV3cisR cells, with IC50 values ranging from 0.104 to 0.341 nmol/L. In A2780cisR and SKOV3cisR xenograft models, tumor growth in CD70‐ADC treated mice was significantly inhibited compared to that in the control‐ADC treated mice (A2780cisR: 32.0 vs 1639.0 mm3, P &lt; .01; SKOV3cisR: 232.2 vs 584.9 mm3, P &lt; .01). Platinum treatment induced CD70 expression in ovarian cancer cells. CD70‐ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

Utilization of sentinel lymph node biopsy in the early ovarian cancer surgery

Sentinel lymph node (SLN) biopsy has been incorporated into surgical care for many malignancies; however, the utility has not been examined in ovarian cancer. This study examined population-level trends, characteristics, and outcomes related to SLN biopsy in early stage ovarian cancer. This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2003-2018. The study population consisted of 11,512 women with stage I ovarian cancer who had adnexectomy-based surgical staging including lymph node evaluation. Exposure allocation was based on SLN biopsy use. Main outcomes measured were (i) trends and characteristics associated with SLN biopsy use, assessed by multivariable logistic regression model, and (ii) overall survival assessed with inverse provability of treatment weighting propensity score. SLN biopsy was performed in less than 1% of study population. In a multivariable analysis, recent surgery (2011-2018 versus 2003-2010, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.03-2.59), smaller tumor size (< 10 versus ≥ 10 cm, OR 3.07, 95% CI 1.20-7.84), and East registry area (OR 2.74, 95% CI 1.73-4.36) remained independent characteristics for SLN biopsy use. In a propensity score weighted model, 5-year overall survival rate was 90.5% for the SLN biopsy-incorporated group and 88.6% for the lymphadenectomy group (hazard ratio 0.96, 95% CI 0.53-1.73). SLN biopsy was rarely performed for early ovarian cancer surgery during the study period with insufficient evidence to interpret the survival effect. SLN biopsy in early ovarian cancer appears to be in early development phase, warranting further study and careful evaluation to assess feasibility and oncologic outcome.

Association between hysterectomy wait-time and all-cause mortality for micro-invasive cervical cancer: treatment implications during the coronavirus pandemic

Treatment specialty‐specific characteristics and outcomes in women with vulvo‐vaginal melanoma: A JGOG‐JSCS joint study

Effect of delay in surgical therapy for early-stage cervical cancer: An implication in the coronavirus pandemic

Financial viewpoint of minimally invasive radical hysterectomy for early cervical cancer: another disadvantage?

Association between hospital surgical volume and perioperative outcomes of fertility-sparing trachelectomy for cervical cancer: A national study in the United States

To examine the association between hospital surgical volume and perioperative outcomes for fertility-sparing trachelectomy performed for cervical cancer. This is a population-based retrospective observational study utilizing the Nationwide Inpatient Sample from 2001 to 2011. Women aged ≤45 years with cervical cancer who underwent trachelectomy were included. Annualized hospital surgical volume was defined as the average number of trachelectomies a hospital performed per year in which at least one case was performed. Perioperative outcomes were assessed based on hospital surgical volume in a weighted model, specifically comparing the top-decile centers to the lower volume centers. There were a total of 815 trachelectomies performed at 89 centers, and 76.4% of the trachelectomy-performing centers had a minimum surgical volume of one trachelectomy per year. The top-decile group had a higher rate of lymphadenectomy performance compared to the lower volume group (96.4% versus 82.4%, odds ratio [OR] 5.65, 95% confidence interval [CI] 2.81-11.4, P < 0.001). There was a significant inverse linear association between annualized surgical volume and the number of perioperative complications (P = 0.020). The top-decile group also had a lower rate of perioperative complications (9.7% versus 21.0%, P < 0.001) and prolonged hospital stay ≥7 days (2.0% versus 6.5%, P = 0.006) compared to the lower volume group. In a multivariable analysis, the top-decile group had a 65% relative decrease in perioperative complication risk compared to the lower volume group (adjusted-OR 0.35, 95%CI 0.20-0.59, P < 0.001). Fertility-sparing trachelectomy for young women with cervical cancer is a rare surgical procedure; <90 centers performed this procedure from 2001 to 2011 and most hospitals perform a small number of cases annually. Higher hospital surgical volume for trachelectomy may be associated with reduced perioperative morbidity.

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

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.

Association between hospital treatment volume and survival of women with gynecologic malignancy in Japan: a JSOG tumor registry-based data extraction study

Associations between hospital treatment volume and survival outcomes for women with 3 types of gynecologic malignancies, and the trends and contributing factors for high-volume centers were examined. The Japan Society of Obstetrics and Gynecology tumor registry databased retrospective study examined 206,845 women with 80,741, 73,647, and 52,457 of endometrial, cervical, and ovarian tumor, respectively, who underwent primary treatment in Japan between 2004 and 2015. Associations between the annual treatment volume and overall survival (OS) for each tumor type were examined using a multivariable Cox proportional hazards model with restricted cubic splines. Institutions were categorized into 3 groups (low-, moderate-, and high-volume centers) based on hazard risks. Hazard ratio (HR) for OS each the 3 tumors decreased with hospital treatment volume. The cut-off points of treatment volume were defined for high- (≥50, ≥51, and ≥27), moderate- (20-49, 20-50, and 17-26), and low-volume centers (≤19, ≤19, and ≤16) by cases/year for endometrial, cervical, and ovarian tumors, respectively. Multivariate analysis revealed younger age, rare tumor histology, and initial surgical management as contributing factors for women at high-volume centers (all, p<0.001). The proportion of high-volume center treatments decreased, whereas low-volume center treatments increased (all p<0.001). Treatment at high-volume centers improved OS than that at other centers (adjusted HR [aHR]=0.83, 95% confidence interval [CI]=0.78-0.88; aHR=0.78, 95% CI=0.75-0.83; and aHR=0.90, 95% CI=0.86-0.95 for endometrial, cervical, and ovarian tumors). Hospital treatment volume impacted survival outcomes. Treatments at high-volume centers conferred survival benefits for women with gynecologic malignancies. The proportion of treatments at high-volume centers have been decreasing recently.

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

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

Characteristics and outcomes of women with adenocarcinoma versus squamous cell carcinoma of the vulva: A Japanese Gynecologic Oncology Group study

Studies on vulvar adenocarcinoma are lacking. Thus, we aimed to compare the characteristics and survival outcomes between vulvar adenocarcinoma and squamous cell carcinoma (SCC). This was a preplanned sub-analysis of a previously organized nationwide retrospective observational study in Japan conducted between 2001 and 2010 (JGOG-1075S). Surgically treated women with stage I-IV vulvar invasive adenocarcinoma were compared to those with SCC. Multivariable analysis was performed to identify patient and tumor characteristics related to adenocarcinoma. Inverse probability of treatment weighting was used to balance the background differences, and a Cox proportional hazards regression model was fitted to estimate the effect of the histological type on survival. Forty-eight women with adenocarcinoma were compared with 537 women with SCC. On multivariable analysis, women with adenocarcinoma were younger (median age, 64.5 vs. 70 years, adjusted odds ratio [OR] per age 0.975, 95% confidence interval [CI] 0.955-0.995, P = 0.016) and had higher positive surgical margin rates (31.2% vs. 18.4%, adjusted OR 2.376, 95% CI 1.188-4.754, P = 0.014) than those with SCC. However, according to the weighted model, the survival outcomes were comparable (hazard ratio for progression-free survival, 1.088, 95% CI 0.740-1.601, P = 0.667 and hazard ratio for overall survival, 1.008, 95% CI 0.646-1.573, P = 0.973). Similar associations were observed when the cohort was stratified by age (≤70 or >70 years), stage (I-II or III-IV), and surgical margin (negative or positive) (all, P > 0.05). Vulvar adenocarcinoma is characterized by a younger age at diagnosis and higher positive surgical margin rates than SCC, but the survival outcomes are comparable.

Recent changes in demographics and outcomes of cervical cancer in the United States

Wait-time for adjuvant radiotherapy and oncologic outcome in early-stage cervical cancer: A treatment implication during the coronavirus pandemic

Transvaginal cervical tumor-concealing no-look no-touch technique in minimally invasive radical hysterectomy for early-stage cervical cancer: a novel operation technique

The Laparoscopic Approach to Cervical Cancer (LACC) trial demonstrated that minimally invasive radical hysterectomy was inferior to the open approach [1]; this unexpected result could be attributed to the spillage of cancer cells [2]. Following the LACC trial, laparoscopic radical hysterectomy without an intrauterine manipulator upon completion of a vaginal cuff closure became the new standard treatment method [3]. However, the lack of intrauterine manipulator results in poor visualization and inadequate paracervical tissue resection. This study describes the no-look no-touch technique to address this difficulty. The core procedures in our no-look, no-touch laparoscopic radical hysterectomy are: (Step 1) Creation and closure of a vaginal cuff; (Step 2) Manipulation of the uterus without an intra-uterine manipulator; and (Step 3) Exposure of the paracervical tissues by the suspension technique. The patient eligibility for our procedure is as follows: 1) previously untreated cervical cancer (those who underwent diagnostic conization could be included); 2) clinical stage IA2, IB1, IB2, and IIA1 based on the 2018 International Federation of Gynecology and Obstetrics staging system; 3) histologically confirmed cervical cancer, including squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma. The important indication for this procedure is in cases where the tumor is less than 4 cm in diameter. We previously reported that our no-look no-touch technique enables smooth performance of laparoscopic radical hysterectomy without worsening oncologic outcomes [4]. According to a recent systematic review and meta-analysis [5], minimally invasive radical hysterectomy with vaginal cuff closure is a safe treatment option; however, it involves a steep learning curve, which has impeded its increased application. This video will hopefully make minimally invasive radical hysterectomy with protective maneuvers against cancer cell spillage more accessible. Based on our experiences, we propose that our transvaginal cervical tumor-concealing no-look no-touch technique will mitigate the risk of surgical spill of tumor cells during minimally invasive radical hysterectomy. The informed consent for use of this video was taken from the patient.

Utilizations and characteristics of ovarian conservation at hysterectomy for cervical carcinoma in situ

AbstractObjectiveTo examine the trends and characteristics of ovarian conservation at time of hysterectomy in cervical carcinoma in situ.MethodsThis is a retrospective cohort study examining the Healthcare Cost and Utilization Project's National Inpatient Sample, January 2016 to December 2019. The study population included 6605 patients aged less than 65 years with cervical carcinoma in situ who underwent hysterectomy. Exposure allocation was the adnexal procedure status (ovarian conservation vs. oophorectomy). Main outcome measures were temporal trends of ovarian conservation over time and per patient age. A classification‐tree was constructed to examine utilization patterns of ovarian conservation.ResultsOvarian conservation was performed in 57.2% of patients. Ovarian conservation rates were unchanged over time (P‐trend = 0.219). Ovarian conservation rates remained stable until age 40 years, ranging from 88.0% to 78.6% (P‐trend = 0.236), after which time the rate sharply decreased from 78.6% to 19.1% (P‐trend &lt;0.001). In a multivariable analysis, younger age, fewer comorbidities, higher household income, vaginal hysterectomy, and surgery at small bed capacity non‐rural hospitals were associated with ovarian conservation (all, P &lt; 0.05). There were 17 utilization patterns of ovarian conservation for which the rate ranged from 17.2% to 94.4% (absolute rate difference 77.2%, P &lt; 0.001).ConclusionDecrease in the utilization of ovarian conservation at hysterectomy for cervical carcinoma in situ occurred at age 40 years, which is earlier than expected.

Utilization of lymph node evaluation at hysterectomy for cervical carcinoma in situ

AbstractBackground and ObjectivesThis study examined the utilization and characteristics of lymph node evaluation at hysterectomy for carcinoma in situ of the uterine cervix.MethodsThis retrospective cohort study queried the Healthcare Cost and Utilization Project's National Inpatient Sample, evaluating 7395 patients with cervical carcinoma in situ who underwent hysterectomy from 2016 to 2019. A multivariable binary logistic regression model was fitted to identify independent characteristics related to lymph node evaluation. A classification‐tree was constructed with recursive partitioning analysis to examine utilization patterns of lymph node evaluation.ResultsLymph node evaluation at hysterectomy was performed in 4.6%. In amultivariable analysis, older age, higher income, use of robotic‐assisted hysterectomy, and surgery at large bed capacity or urban teaching centers in the northeast US region were associated with increased likelihood of lymph node evaluation (all, p &lt; 0.05). Of those independent factors, robotic‐assisted surgery exhibited the largest effect size (adjusted odds ratio 3.23, 95% confidence interval 2.54–4.10). Utilization pattern analysis identified nine unique characteristics, of which robotic‐assisted surgery was the primary indicator for cohort allocation (12.4% vs. 3.2%, p &lt; 0.001). The difference between the lowest–highest patterns was 33.3% (range, 0%–33.3%).ConclusionLymph node evaluation was rarely performed for cervical carcinoma in situ overall and robotic surgery was associated with increased utilization of lymph node evaluation.

Metastatic extent-specific prognosis of women with stage IVB cervical cancer: multiple versus single distant organ involvement

Despite the heterogeneity of anatomical sites that metastases may affect, within the current cancer staging schematic, stage IVB encompasses all distant metastasis. This study examined survival outcomes based on the extent of distant organ metastasis in stage IVB cervical cancer. This retrospective cohort study utilized the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2010 to 2018. The study population included 1772 women with stage IVB cervical cancer who had tumor metastasis to one or more of the following four organs: bone, brain, liver, or lung. Overall survival was assessed based on the metastatic extent in multivariable analysis. The most common metastatic site was lung (68.3%) followed by bone (35.2%), liver (30.0%), and brain (1.2%). Multiple organ metastases were seen in 26.5% of study population, with lung / liver metastases being the most frequent combination pattern (9.6%) followed by lung / bone (9.4%), and lung / bone / liver (6.4%). A total of 1442 (81.4%) deaths occurred during the follow-up. The cohort-level median overall survival was 7 months, ranging from 3 months in all four organ metastases to 11 months in bone metastasis alone when stratified (absolute difference 8 months, P < 0.001). Multiple organ metastases were independently associated with nearly 50% increased all-cause mortality risk compared to single organ metastasis (adjusted-hazard ratio 1.51, 95% CI 1.34-1.70). Survival outcomes in those with stage IVB cervical cancer with distant organ involvement can vary based on the extent of metastasis. Incorporation of single versus multiple distant organ metastasis into the cancer staging schema may be valuable (IVB1 versus IVB2).

Significance of histology and nodal status on the survival of women with early-stage cervical cancer: validation of the 2018 FIGO cervical cancer staging system

To assess the efficacy of the FIGO 2018 classification system for nodal-specific classifications for early-stage cervical cancer; specifically, to examine the impact of nodal metastasis on survival and the effect of postoperative treatments, according to histological subtypes. This society-based retrospective observational study in Japan examined 16,539 women with the 2009 FIGO stage IB1 cervical cancer who underwent primary surgical treatment from 2004 to 2015. Associations of cause-specific survival (CSS) with nodal metastasis and postoperative adjuvant therapy were examined according to histology type (squamous cell carcinoma [SCC], n=10,315; and non-SCC, n=6,224). The nodal metastasis rate for SCC was higher than that for non-SCC (10.7% vs. 8.3%, p<0.001). In multivariable analysis, the impact of nodal metastasis on CSS was greater for non-SCC tumors (adjusted-hazard ratio [HR], 3.11; 95% confidence interval [CI], 2.40-4.02) than for SCC tumors (adjusted-HR, 2.20; 95% CI, 1.70-2.84; p<0.001). Propensity score matching analysis showed significantly lower CSS rates for women with pelvic nodal metastasis from non-SCC tumors than from SCC tumors (5-year CSS rate, 75.4% vs. 90.3%, p<0.001). The CSS rates for women with nodal metastasis in SCC histology were similar between the postoperative concurrent chemoradiotherapy/radiotherapy and chemotherapy groups (89.2% vs. 86.1%, p=0.42), whereas those in non-SCC histology who received postoperative chemotherapy improved the CSS (74.1% vs. 67.7%, p=0.043). The node-specific staging system in the 2018 FIGO cervical cancer classification is applicable to both non-SCC tumors and SCC tumors; however, the prognostic significance of nodal metastases and efficacy of postoperative therapies vary according to histology.

Contraception and sterilization selection at delivery among pregnant patients with malignancy

AbstractIntroductionSince malignancy during pregnancy is uncommon, information regarding contraception selection or sterilization at delivery is limited. The objective of this study was to examine the type of long‐acting reversible contraception or surgical sterilization procedure chosen by pregnant patients with malignancy at delivery.Material and methodsThis cross‐sectional study queried the Healthcare Cost and Utilization Project's National Inpatient Sample in the USA. The study population was vaginal and cesarean deliveries in a hospital setting from January 2017 to December 2020. Pregnant patients with breast cancer (n = 1605), leukemia (n = 1190), lymphoma (n = 1120), thyroid cancer (n = 715), cervical cancer (n = 425) and melanoma (n = 400) were compared with 14 265 319 pregnant patients without malignancy. The main outcome measures were utilization of long‐acting reversible contraception (subdermal implant or intrauterine device) and performance of permanent surgical sterilization (bilateral tubal ligation or bilateral salpingectomy) during the index hospital admission for delivery, assessed with a multinomial regression model controlling for clinical, pregnancy and delivery characteristics.ResultsWhen compared with pregnant patients without malignancy, pregnant patients with breast cancer were more likely to proceed with bilateral salpingectomy (adjusted odds ratio [aOR] 2.30) or intrauterine device (aOR 1.91); none received the subdermal implant. Pregnant patients with leukemia were more likely to choose a subdermal implant (aOR 2.22), whereas those with lymphoma were more likely to proceed with bilateral salpingectomy (aOR 1.93) and bilateral tubal ligation (aOR 1.76). Pregnant patients with thyroid cancer were more likely to proceed with bilateral tubal ligation (aOR 2.21) and none received the subdermal implant. No patients in the cervical cancer group selected long‐acting reversible contraception, and they were more likely to proceed with bilateral salpingectomy (aOR 2.08). None in the melanoma group chose long‐acting reversible contraception. Among pregnant patients aged &lt;30, the odds of proceeding with bilateral salpingectomy were increased in patients with breast cancer (aOR 3.01), cervical cancer (aOR 2.26) or lymphoma (aOR 2.08). The odds of proceeding with bilateral tubal ligation in pregnant patients aged &lt;30 with melanoma (aOR 5.36) was also increased.ConclusionsThe results of this nationwide assessment in the United States suggest that among pregnant patients with malignancy, the preferred contraceptive option or method of sterilization at time of hospital delivery differs by malignancy type.

Clinical and pathological characteristics and outcomes of small cell neuroendocrine carcinoma of the uterine cervix

To describe the clinical and pathological characteristics and outcomes of small cell neuroendocrine carcinoma of the uterine cervix at the population level in the United States. The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried. The study population included 54,987 patients with cervical cancer from 2004 to 2021. Descriptive analysis was performed based on histology. Histology types included squamous cell carcinoma (n = 38,145, 69.4%), adenocarcinoma (n = 14,333, 26.1%), adenosquamous carcinoma (n = 1,970, 3.6%), and small cell neuroendocrine carcinoma (n = 539, 1.0%). Over the 18-year study period, the incidence rate of small cell neuroendocrine carcinoma increased by 3.2% per year (95% CI 1.2 to 5.7, p = .003). Based on this trajectory, the incidence of small cell neuroendocrine carcinoma is estimated to reach 2.0% by 2035. Small cell neuroendocrine carcinoma was associated with larger cervical tumors (60 mm versus 27-40 mm), a higher lymph node metastasis ratio (25.0% versus 14.3%-15.4%), higher distant metastasis rate even in small tumor (10 mm, 10.3% versus 0.5-2.6%; and 20 mm, 14.8% versus 3.9-5.3%), and stage IV disease (40.1% versus 11.9%-15.2%) than other histologies (p < .001). Among distant metastasis cases, small cell neuroendocrine carcinoma was more likely to spread to the liver (36.1% versus 14.3%-15.4%) or bone (28.8% versus 17.3%-19.1%) and to involve multiple distant organ metastases (≥2 organs: 37.3% vs 27.8%-30.2%; and ≥3 organs: 18.1% vs 9.2%-10.1%) compared with other histologies (p < .001). Across stages I to IV, small cell neuroendocrine carcinoma had lower 5-year overall survival rates than other histologies: stage I, 58.0% versus 82.5% to 91.3%; stage II, 38.4% versus 60.7% to 64.6%; stage III, 31.3% versus 49.5% to 51.4%; and stage IV, 8.1% versus 18.2% (p < .05). Early-death rates within two months from diagnosis of small cell neuroendocrine carcinoma were substantially higher than other histologies (9.0% vs 2.2%, p < .001). This population-based assessment suggests that, although rare, the incidence of small cell neuroendocrine carcinoma of the uterine cervix is gradually increasing in the United States. Multiple distant organ metastases, especially to the liver and bone, and poor survival outcomes characterize small cell neuroendocrine carcinoma of the uterine cervix.

Modified radical hysterectomy for stage IB1 (≤2 cm) cervical cancer: assessment of temporal trends and oncologic outcomes in the United States

The oncologic safety of less-radical surgery for early-stage cervical cancer is currently being actively investigated. Given the paucity of data, this study assessed the temporal trends and oncologic outcomes associated with modified radical hysterectomy for stage IB1 (≤2 cm) cervical cancer in the United States. This retrospective cohort study used data from the Commission-on-Cancer's National Cancer Database. The study population was 2902 patients with clinical stage IB1 (≤2 cm) cervical cancer from 2010 to 2020. Temporal trends based on hysterectomy modality (radical hysterectomy, modified radical hysterectomy, and simple hysterectomy) were assessed using linear segmented regression with log-transformation, and the overall survival was assessed using a multivariable Cox proportional hazard regression model. There was a statistically significant increase in modified radical hysterectomy from 2013 to 2020 (annual percentage rate increase 4.4, 95% CI 0.7 to 16.0, p=.040) and a decrease in simple hysterectomy from 2012 to 2020 (-2.3, 95% CI -3.7 to -1.3, p<.001). The lymphovascular space invasion rates (26.8%, 26.8%, and 23.1% for the radical, modified radical, and simple hysterectomy groups, respectively, p=.10) and pathological nodal metastasis rates (5.0%, 4.4%, and 4.0%, respectively, p=.54) were similar among the 3 groups. The use of adjuvant radiotherapy was higher in the simple hysterectomy group (13.0%, 13.0%, and 18.2% in the radical, modified radical, and simple hysterectomy groups, respectively, p<.001). The 5-year overall survival rates for radical hysterectomy, modified radical hysterectomy, and simple hysterectomy were 96.6%, 96.3%, and 95.8%, respectively (p=.66). In multivariable analysis, modified radical hysterectomy (adjusted HR 1.23, 95% CI 0.73 to 2.06) and simple hysterectomy (adjusted HR 1.02, 95% CI 0.70 to 1.48) were not associated with decreased overall survival compared with radical hysterectomy. The results of this cohort study in the United States suggest that modified radical hysterectomy for stage IB1 (≤2 cm) may not be associated with overall survival. This observed survival association warrants further investigation for stage IB1 (≤2 cm) cervical cancer that does not meet the low-risk criteria.

Relative survival of large cell to small cell neuroendocrine carcinoma of the uterine cervix.

This retrospective study compared clinico-pathological characteristics and survival of large cell to small cell neuroendocrine carcinomas of the uterine cervix identified in the Commission-on-Cancer's National Cancer Database from 2004 to 2022 (n = 2051). Large cell neuroendocrine carcinoma, reported in 16.3%, was more likely to be T1 classification (37.1% vs 29.5%) and have smaller cervical tumor (median size, 47 and 59 mm) but less likely to be T3 classification (15.6% vs 22.4%) and N1 classification (36.8% vs 45.1%) than small cell neuroendocrine carcinoma (all, p < .05). In propensity score inverse probability of treatment weighting, large cell neuroendocrine carcinoma had overall survival comparable to small cell neuroendocrine carcinoma (5-year rates, 33.8% vs 30.9%, hazard ratio 1.02, 95% confidence interval 0.86 to 1.20). This survival association was consistent across stage I, II, III, and IV diseases. In the secondary cohort of the National Cancer Institute's Surveillance, Epidemiology, and End Results Program, cause-specific survival from cervical cancer was similar between large cell and small cell neuroendocrine carcinomas (5-year rates, 36.1% vs 39.1%, hazard ratio 1.25, 95% confidence interval 0.88 to 1.76). In conclusion, these data suggest that large cell neuroendocrine carcinoma represents less than 20% of neuroendocrine carcinomas of the uterine cervix, and although tumor characteristics appear to be less aggressive, oncologic outcomes are dismal and similar to small cell neuroendocrine carcinoma.

Clinico-pathological characteristics and survival outcome associated with uterine leiomyosarcoma variants: epithelioid and myxoid types

Epithelioid and myxoid types represent uterine leiomyosarcoma variants, and their clinico-pathologic characteristics and survival outcomes have been under-studied because of their rarity. The objective of this study was to assess clinico-pathologic characteristics and survival associated with uterine leiomyosarcoma variants. This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. The study population included 7410 patients with uterine leiomyosarcoma, including conventional, epithelioid, and myxoid types, who had primary hysterectomy from 2010 to 2022. Demographic characteristics were assessed using descriptive analysis; overall survival was assessed using a multivariable Cox proportional hazards regression model. Epithelioid and myxoid types were reported in 478 (6.5%) and 327 (4.4%) patients, respectively. The proportion of the epithelioid variant increased from 5.5% in 2010-2014 to 7.8% in 2019-2022 (p = .005). The epithelioid type was associated with higher rates of lympho-vascular space invasion (33.1% vs 22.0%-23.7%) and nodal metastasis (6.9% vs 3.4%-3.6%), whereas the myxoid type was associated with a higher rate of stage I disease (64.5% vs 56.1%-58.7%) (all, p < .05). Compared with the conventional type, the epithelioid type was associated with improved overall survival (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.75 to 0.99) including stage I (aHR 0.75, 95%CI 0.60 to 0.93) and stage III (aHR 0.59, 95% CI 0.39 to 0.91) disease; the myxoid type was also associated with improved overall survival (aHR 0.68, 95%CI 0.57 to 0.82) including stage I (aHR 0.62, 95% CI 0.47 to 0.82) and stage IV (aHR 0.60, 95% CI 0.41 to 0.88) disease. Across all three types, larger tumor size, lympho-vascular invasion, and higher stage were associated with decreased overall survival, with the survival impact of larger tumor size being more prominent in variants. For stage II to IV epithelioid type, adjuvant chemotherapy was associated with improved overall survival (aHR 0.43, 95% CI 0.29 to 0.64). The results of this cohort study suggest that uterine leiomyosarcoma variants (epithelioid and myxoid) exhibit distinct histopathologic characteristics and survival compared with the conventional type. These data also endorse the importance of accurate diagnosis, research inclusion criteria, and development of collaborative networks.

Assessment of overall survival in reproductive-age patients with 2023 International Federation of Gynecology and Obstetrics stage IA1 grade 1 endometrioid endometrial cancer

This study aimed to assess the overall survival of reproductive-age patients with non-myoinvasive stage IA1 grade 1 endometrioid endometrial cancer. This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database. The study population included 21,248 patients with grade 1 endometrioid endometrial cancer with the 2023 International Federation of Gynecology and Obstetrics stage IA1 (tumor with no myoinvasion; n = 6249), IA2 (tumor with inner-half myoinvasion; n = 11,113), and IB (tumor with outer-half myoinvasion; n = 3886), who had primary hysterectomy from 2010 to 2015. The main outcome measures were 5- and 10-year overall survival rates according to patient age (<40, 40-49, and ≥50 years) and cancer stage (IA1, IA2, and IB) stratifications. Stage IA1 was the most frequent sub-stage until age 45 years. The median follow-up was 8.3 (interquartile range; 6.8-10.0) years. Among patients aged <40 years, the 5- and 10-year overall survival rates were 100% and 98.7% (95% confidence interval [CI] 94.7 to 99.7) for stage IA1, 97.6% (95% Cl 94.7 to 98.9) and 94.4% (95% CI 88.1 to 97.4) for stage IA2, and 100% and 95.2% (95% CI 82.3 to 98.8) for stage IB, respectively (p-overall = .009). Among patients aged 40 to 49 years, the 5- and 10-year overall survival rates were 99.3% (95% CI 98.4 to 99.7) and 96.5% (95% CI 94.4 to 97.8) for stage IA1, 98.1% (95% Cl 96.9 to 98.8) and 94.4% (95% CI 92.1 to 96.0) for stage IA2 and 96.0% (95% CI 90.6 to 98.3) and 86.5% (95% CI 77.5 to 92.0) for stage IB, respectively (p-overall < .001). Among patients aged ≥50 years, the 5- and 10-year overall survival rates were 96.2% (95% CI 85.6 to 96.7) and 88.5% (95% CI 87.3 to 89.6) for stage IA1, 94.9% (95% CI 94.4 to 95.3) and 85.7% (95% CI 84.8 to 86.6) for stage IA2, and 92.1% (95% CI 91.2 to 93.0) and 78.0% (95% CI 76.3 to 79.6) for stage IB, respectively (p-overall < .001). This cohort study found that reproductive-age patients, particularly, adolescent and young adults, with non-myoinvasive stage IA1 grade 1 endometrioid endometrial cancer have favorable prognosis. These data may be used as the benchmark setting the foundation for future investigation on fertility-sparing options.

Identifying the possible candidate population for adjuvant radiotherapy de-escalation for intermediate-risk cervical cancer.

To explore whether there is a possible candidate population for treatment de-escalation with active surveillance without adjuvant radiotherapy for patients with stage IB cervical cancer meeting the intermediate-risk criteria. This retrospective cohort study queried the Commission-on-Cancer's National Cancer Database in the United States. The study population included 1133 patients with node-negative, parametria-free, surgical margin-uninvolved, stage IB intermediate-risk cervical cancer (tumor size 2-4 cm with lymphovascular space invasion, or tumor size of >4 cm regardless of lymphovascular space invasion) who had primary radical hysterectomy and lymph node evaluation from 2010 to 2022. Exposure was adjuvant radiotherapy status: external beam radiotherapy with or without chemotherapy (n = 642) or active surveillance without radiotherapy (n = 491). The main outcome measure was overall survival, assessed in a propensity score inverse probability of treatment weighting cohort. At the whole-cohort level, hazard ratio (HR) for all-cause mortality comparing adjuvant radiotherapy de-escalation to adjuvant radiotherapy was 1.31 (95% confidence interval [CI] 0.92 to 1.86, p = .13). When stratified by histology type, adjuvant radiotherapy de-escalation was associated with increased all-cause mortality risk in squamous cell carcinoma (HR 1.55, 95% CI 1.02 to 2.34, p = .038) but not in adenocarcinoma or adenosquamous carcinoma (HR, 0.90; 95% CI 0.46 to 1.75, p = .75). When stratified by tumor differentiation, adjuvant radiotherapy de-escalation was associated with increased all-cause mortality risk in poorly-differentiated tumors (HR, 2.11; 95% CI 1.29 to 3.42, p =.003) but not in well- to moderately-differentiated tumors (HR, 0.83; 95% CI 0.50 to 1.37, p = .47). The results of this cohort study in the United States suggest that overall survival benefits of adjuvant radiotherapy for study-defined intermediate-risk stage IB cervical cancer may vary based on histology type and tumor differentiation. Specifically, patients with squamous cell carcinoma or poorly-differentiated tumors benefited from receiving adjuvant radiotherapy, while those with adenocarcinoma/adenosquamous carcinoma or well- to moderately-differentiated tumors did not. Whether there may be candidates for treatment de-escalation in intermediate-risk cervical cancer warrants further investigation with a prospective design.

Validation of the 2023 FIGO staging system and its concordance with the JSGO guidelines in endometrial cancer: A multi‐institutional retrospective study in Japan

Abstract Aim To validate the prognostic accuracy of the 2023 FIGO staging system and assess its alignment with the Japan Society of Gynecologic Oncology (JSGO) guidelines for endometrial cancer treatment. Methods This retrospective cohort study included 1207 patients with endometrial cancer treated at four academic hospitals in Kanagawa, Japan, between 2018 and 2022. Patients were reclassified according to the FIGO 2023 system and the JSGO recurrence risk categories. Primary endpoints included stage migration, recurrence risk (RR), overall survival (OS), and concordance between the two classification systems. Results Under FIGO 2023, the stage distribution was: I, 741 (61.4%); II, 203 (16.8%); III, 149 (12.3%); and IV, 114 (9.4%), with stage migration observed in 36.3% of cases. The FIGO 2023 system provided clearer stratification of 3‐year RR than FIGO 2009, with the RR gap widening from 80.0% to 90.1%. Sixteen patients (3.5%) with stage IA3 were classified as high risk by JSGO criteria, while 14.4% of patients considered high risk by JSGO were downstaged under FIGO 2023. Additionally, 46 patients (19.6%) with FIGO stage IA were reclassified as intermediate risk owing to focal lymphovascular space invasion (LVSI). Substantial LVSI was significantly associated with recurrence and poor prognosis (3‐year OS rates: none 94.3%, focal 89.9%, and substantial 40.7%; p  &lt; 0.05). Molecular testing was limited: p53 in 30.2%, MSI in 5.9%, and POLE was not available. Conclusions FIGO 2023 improves prognostic precision. Incorporating LVSI extent and molecular data may refine JSGO classifications and support more individualized adjuvant therapy strategies.

International Federation of Gynecology and Obstetrics 2023 stage IIIB2 endometrial cancer with pelvic peritoneal metastasis: assessment of adjuvant therapy effect on survival

The 2023 International Federation of Gynecology and Obstetrics (FIGO) endometrial cancer staging schema classifies pelvic peritoneum only metastasis as stage IIIB2 disease. In this retrospective cohort study of 193 patients with FIGO 2023 stage IIIB2 endometrial cancer who underwent primary hysterectomy from 2006 to 2015 identified in the Commission-on-Cancer's National Cancer Database, systemic chemotherapy without external beam radiotherapy was the most frequent adjuvant therapy type (48.7%), followed by combination systemic chemotherapy and external beam radiotherapy (42.0%) and external beam radiotherapy without systemic chemotherapy (9.3%). After controlling for patient age, race and ethnicity, co-morbidity, and histology, combination systemic chemotherapy and external beam radiotherapy was associated with 40% reduction of all-cause mortality compared with systemic chemotherapy without external beam radiotherapy (5-year rates: 63.1% vs 45.7%, adjusted-hazard ratio 0.60, 95% confidence interval 0.40-0.92). This reduction of all-cause mortality for combination systemic chemotherapy and external beam radiotherapy compared with systemic chemotherapy without external beam radiotherapy increased to 55% among non-endometrioid histology (5-year overall survival rates: 52.0% vs 33.4%, adjusted-hazard ratio 0.45, 95% confidence interval 0.23-0.88). In conclusion, the results of this investigation suggest that, despite peritoneal disease spread, multi-modal treatment with combination systemic and local therapies may improve survival in FIGO 2023 stage IIIB2 endometrial cancer, especially in non-endometrioid histology.

Estimating high-grade serous fallopian tubal carcinoma in the era of tubal hypothesis

In the era of the serous tubal intraepithelial carcinoma hypothesis, investigation continues as to what proportions of high-grade serous tubo-ovarian carcinomas originate in the distal fallopian tube versus in the ovary. In this retrospective cohort study of 118,619 patients with high-grade serous tubo-ovarian carcinoma identified in the Commission-on-Cancer's National Cancer Database from 2004 to 2021, a diagnosis shift from high-grade serous ovarian carcinoma to high-grade serous fallopian tubal carcinoma occurred from 2004 to 2018 that the proportional distribution of high-grade serous fallopian tubal carcinoma increased 6.1-fold from 4.5% in 2004 to 27.6% in 2018 (p-trend < .001). This rapid diagnosis shift from high-grade serous ovarian carcinoma to high-grade serous fallopian tubal carcinoma reached a plateau at 2018, followed by steady proportional distribution of high-grade serous fallopian tubal carcinoma among the high-grade serous tubo-ovarian carcinomas for 4 consecutive years (27.6% in 2018 to 28.0% in 2021, p-trend = .801). The average rate of tubal carcinomas during this post-plateau period was 27.7%. In conclusion, the diagnosis shift in the primary site of high-grade serous tubo-ovarian carcinoma from the ovary to the fallopian tube may have ended in the late 2010s. After the implementation of College of American Pathologists diagnosis criteria, 1 in 3 to 4 high-grade serous tubo-ovarian carcinomas were classified as of fallopian tube origin.

Cost-effectiveness analysis of hospital treatment volume and survival outcomes in endometrial cancer in Japan

Hospital treatment volume affects survival in patients with endometrial cancer; notably, initial treatment at high-volume centers improves survival outcomes. Our study assessed the effect of hospital treatment volume on cost-effectiveness and survival outcomes in patients with endometrial cancer in Japan. A decision-analytic model was evaluated using the following variables and their impact on cost-effectiveness: 1) hospital treatment volume (low-, intermediate-, and high-volume centers) and 2) postoperative recurrent risk factors based on pathological findings (high- and intermediate-risk or low-risk). Data were obtained from the Japan Society of Obstetrics and Gynecology database, systematic literature searches, and the Japanese Diagnosis Procedure Combination database. Quality-adjusted life years (QALY) was used as a measure of effectiveness. The model was built from a public healthcare perspective and the impact of uncertainty was assessed using sensitivity analyses. A base-case analysis showed that the incremental cost-effectiveness ratio at high-volume centers was below a willingness-to-pay (WTP) threshold of ¥5,000,000 with a maximum of ¥3,777,830/4.28 QALY for the high- and intermediate-risk group, and ¥2,316,695/4.57 QALY for the low-risk group. Treatment at the high-volume centers showed better efficiency and cost-effectiveness in both strategies compared to intermediate- or low-volume centers. Sensitivity analyses showed that the model outcome was robust to changes in input values. With the WTP threshold, treatment at high-volume centers remained cost-effective in at least 73.6% and 78.2% of iterations for high- and intermediate-risk, and low-risk groups, respectively. Treatment at high-volume centers is the most cost-effective strategy for guiding treatment centralization in patients with endometrial cancer.

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.

Endometrial Cancer Screening in High-risk Populations

Endometrial cancer is one of the most common malignancies of the reproductive system. The incidence of endometrial cancer has increased in recent years. No effective, low-cost screening method for populations at high risk exists. The traditional methods of endometrial cancer screening and diagnosis (segmented scraping and hysteroscopic biopsy) are invasive examinations with high medical costs. It is urgent to establish a reasonable, effective, economical, and non-invasive endometrial cancer screening strategy. This study aims to evaluate the effectiveness and feasibility of transvaginal ultrasound and microscale endometrial sampling biopsy in screening for endometrial precancerous lesions and endometrial cancer among high-risk populations in China, and to conduct cost-effectiveness analysis of different screening strategy, ultimately guiding the development of screening strategies that are suitable for high-risk populations in China.