BACKGROUND:The therapeutic value of lymphadenectomy in endometrial cancer remains controversial, particularly in high-risk patients as defined by the European Society of Gynaecological Oncology-European Society for Radiotherapy and Oncology 2021 histologic and molecular classification. While pelvic and para-aortic lymphadenectomy is the standard of care for high-risk endometrial cancer, sentinel lymph node (SLN) mapping has emerged as a promising alternative for low-risk patients with reduced post-operative morbidity. Recently, the advent of molecular classification has significantly influenced the diagnosis and management of endometrial cancer. In particular, p53 mutation has been recognized as an important prognostic marker and has been included in the criteria for high-risk classification. PRIMARY OBJECTIVE:To evaluate the impact of SLN mapping versus pelvic and para-aortic lymphadenectomy on disease-free survival at 3 years in high-risk patients with endometrial cancer with p53 mutation and a negative pre-operative positron emission tomography computed tomography scan. STUDY HYPOTHESIS:SLN mapping will provide non-inferior survival outcomes compared with pelvic and para-aortic lymphadenectomy in this population, with reduced post-operative morbidity. TRIAL DESIGN:This is a prospective, multicentre, non-inferiority, open-label, de-escalation, randomized, controlled trial in patients with International Federation of Gynecology and Obstetrics 2023 stage I and II endometrial cancer with p53 mutation and negative pre-operative positron emission tomography computed tomography scans. Patients will be randomized 1:1 to SLN mapping or pelvic and para-aortic lymphadenectomy. MAJOR INCLUSION/EXCLUSION CRITERIA:Eligible participants are aged ≥18 years, with International Federation of Gynecology and Obstetrics 2023 stage I or II endometrial cancer confirmed by magnetic resonance imaging, a p53 mutation verified by biopsy, and planned surgery including total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy if indicated. Exclusion criteria include recurrent endometrial cancer, prior chemotherapy, radiotherapy, endocrine therapy, or contraindications to lymphadenectomy or laparoscopy. PRIMARY ENDPOINT:Disease-free survival at 36 months. SAMPLE SIZE:A total of 374 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS:Estimated completion of recruitment in September 2028, with 36 months of follow-up completed by September 2031. TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT06900582.

OBJECTIVE:To evaluate the impact of secondary cytoreductive surgery (SCS) on overall survival (OS) and progression-free survival (PFS) in patients with recurrent low-grade serous ovarian cancer. METHODS:A multicenter study was conducted, including 152 patients with recurrent low-grade serous ovarian cancer treated across 31 French centers from 2002 to 2024 from the Tumeurs Malignes Rares Gynécologiques network. Patients were analyzed based on SCS status, completeness of cytoreduction (CC0 vs. CC+), and clinical outcomes. Survival analyses were performed using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS:From 478 patients, a total of 152 patients with first recurrent low-grade serous ovarian cancer were included, with 39.5% undergoing SCS. Complete cytoreduction (CC0) was achieved in 92% of cases, with no difference in complication rates based on resection quality. After adjustment on confounding factors, SCS was independently associated with improved OS (adjusted hazard ratio on age [HRa]=0.28; 95% confidence interval [CI]=0.13-0.63; p<0.001) and showed better PFS also not statistically significant (HRa=0.57; 95% CI=0.32-1.03; p=0.06). CONCLUSION:SCS achieving complete resection significantly improves OS and appears to prolong PFS in recurrent low-grade serous ovarian cancer. Proper patient selection is critical to optimizing outcomes. These findings support the integration of SCS into the multidisciplinary management of recurrent low-grade serous ovarian cancer.

INTRODUCTION:In high-grade serous ovarian carcinoma (HGSOC), time to first recurrence is a major prognostic factor guiding therapeutic management. However, this parameter remains poorly studied in low-grade serous ovarian carcinoma (LGSOC), a rare subtype characterized by indolent progression and marked chemoresistance. Moreover, AGO criteria for selecting candidates for secondary cytoreductive surgery appear poorly applicable to LGSOC, highlighting the need for specific prognostic markers. METHODS:We conducted a multicenter retrospective study using the national LGSC database from the French Rare Malignant Gynaecologic Tumor Network. Patients with recurrent LGSOC were included. Associations between time to first recurrence, post-relapse survival (PRS), and post-relapse progression-free survival (PR-PFS) were assessed using Cox proportional hazards models adjusted for established prognostic factors. The association between time to recurrence and completeness of secondary cytoreduction was evaluated using multivariable logistic regression. RESULTS:Among 211 patients, the median time to first recurrence was 32 months (IQR 19-63). Longer recurrence intervals were associated with improved outcomes. In multivariable analysis, patients relapsing at 24-48 months (PRS: HR 0.50; 95% CI 0.25-0.97) and ≥48 months (PRS: HR 0.25; 95% CI 0.11-0.58) had significantly better survival compared with the 12-24 month group. Similar results were observed for PR-PFS, with a significant benefit for ≥48 months (HR 0.36; 95% CI 0.19-0.70). Incorporating time to recurrence improved model discrimination. Time to recurrence was not associated with completeness of secondary cytoreduction. CONCLUSION:Time to first recurrence is an independent prognostic factor in LGSOC. Its integration into prognostic models may improve patient stratification and refine selection for secondary cytoreductive surgery.

Objectives To evaluate the surgical management and oncologic outcomes of patients with FIGO stage IV ovarian cancer, using data from the French national ESME cohort. Methods This retrospective multicenter study included patients diagnosed with FIGO stage IV ovarian cancer between January 2011 and December 2016, treated in 18 French Comprehensive Cancer Centers participating in the ESME-OVR program. Clinical characteristics, treatment strategies, metastatic site patterns, and survival outcomes (overall survival [OS], progression-free survival [PFS]) were analyzed and compared between FIGO IVA and IVB stages. Results A total of 159 patients were identified, of whom 107 (67.3 ​%) had FIGO stage IVB disease. Regardless of metastatic stage, surgical strategies and were comparable. Complete debulking surgery was achieved in 75 ​% of cases. Most of FIGO stage IVB patients (88.8 ​%) presented a single metastatic site including extra-abdominal lymph nodes (50.5 ​%), liver (20.6 ​%), and lungs (10.3 ​%); 15.9 ​% of patient with distant metastases underwent local treatment and predominantly targeted nodal disease. Complete debulking surgery was significantly associated with improved OS and PFS (p ​= ​0.002 and p ​< ​0.001, respectively), while local treatment of metastases did not provide survival benefit. The number of metastatic sites did not significantly influence prognosis. Conclusions Complete debulking surgery is the critical factor from a progronostic point of view, whether in FIGO stage IVA or IVB. Feasibility of local treatment for distant metastases is observed, its impact on oncologic outcomes remains unclear and we need further prospective investigation. Surgical strategies should be integrated into a personalized approach to optimize management in advanced-stage disease.

OBJECTIVE:The aim of this study was to compare surgical complexity, post-operative complications, and survival outcomes between patients with minimal residual disease (completeness of cytoreduction (CC) score) CC-1 at the time of primary debulking surgery and those with complete cytoreduction (CC-0) at the time of interval debulking surgery. METHODS:A retrospective multicenter study was conducted of patients with advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage IIIC-IV) who underwent cytoreductive surgery achieving either minimal or no residual disease between January 2008 and December 2015. Patients underwent either primary or interval debulking surgery after receiving ≥3 cycles of neoadjuvant chemotherapy. The sub-group of patients with primary debulking surgery/CC-1 was compared with those with interval debulking surgery/CC-0. Overall survival and disease-free survival were estimated using the Kaplan-Meier method. RESULTS:A total of 549 patients were included, with upfront surgery performed in 175 patients (31.9%) and 374 patients (68.1%) undergoing interval debulking surgery. After primary debulking surgery, 157/175 (89.7%) had complete cytoreduction and 18/175 (10.3%) had minimal residual disease (primary debulking surgery/CC-1 group), while after interval debulking surgery, 324/374 (86.6%) had complete cytoreduction (interval debulking surgery/CC-0 group) and 50/374 (13.4%) had minimal residual disease. The rate of patients with peritoneal cancer index >10 was 14/17 (82.4%) for the primary debulking surgery/CC-1 group and 129/322 (40.1%) for the interval debulking surgery/CC-0 (p<0.001). The rate of patients with an Aletti score of ≥8 was 11/18 (61.1%) and 132/324 (40.7%), respectively (p=0.09) and the rate of major post-operative complications was 5/18 (27.8%) and 64/324 (19.8%), respectively (p=0.38). Overall median disease-free and overall survival were 19.4 months (95% CI 18.0 to 20.6) and 56.7 months (95%CI 50.2 to 65.8), respectively. Median disease-free survival for the primary debulking surgery/CC-1 group was 16.7 months (95% CI 13.6 to 20.0) versus 18.2 months (95% CI 16.4 to 20.0) for the interval debulking surgery/CC-0 group (p=0.56). Median overall survival for the primary debulking surgery/CC-1 group was 44.7 months (95% CI 34.3 to not reached) and 49.4 months (95% CI 46.2 to 57.3) for the interval debulking surgery/CC-0 group (p=0.97). CONCLUSIONS:Patients with primary debulking surgery with minimal residual disease and those with interval debulking surgery with no residual disease had similar survival outcomes. Interval surgery should be considered when achieving absence of residual disease is challenging at upfront surgery, given the lower tumor burden found during surgery.

OBJECTIVE:To assess the knowledge, practices, and referral patterns of health care professionals and fertility preservation specialists regarding fertility preservation in gynecologic oncology in France. METHODS:In this cross sectional study, an electronic questionnaire was distributed between June 2023 and January 2024 to health care professionals in metropolitan and overseas territories. It included sections on demographics, fertility preservation practices, and technical knowledge, with tailored sections for physicians who are specialists and non-specialists in reproductive medicine. RESULTS:Sixty-four professionals participated (mean experience: 12 years); 65.6% (42/64) were gynecologic surgeons, and 18.8% (12/64) were specialists in reproductive medicine. Among non-specialists (52/64), 82.7% (43/52) routinely discussed fertility with patients of childbearing age, and 94.2% (49/52) had referred patients for fertility preservation. The mean knowledge score was 1.4/6. Only 23.1% (12/52) reported having written materials for patients, and 65.4% (34/52) indicated that no fertility specialist was present at multidisciplinary meetings. All reproductive medicine specialists (n = 12) reported access to oocyte and ovarian tissue cryopreservation, but 83.3% (10/12) believed patients were under-referred. They emphasized the need for systematic discussions of fertility preservation in multidisciplinary settings and highlighted risks associated with ovarian stimulation and tissue reimplantation. The upper age limit for oocyte cryopreservation was generally under 40 years. Pregnancy outcomes following fertility preservation were limited, primarily in cases of borderline ovarian tumors. CONCLUSIONS:Fertility preservation is recognized as a critical component of gynecologic oncology care, but significant gaps remain in knowledge, referrals, and integration into multidisciplinary care. Strengthening collaboration between oncology and fertility teams, standardizing care pathways, and enhancing education for health care providers are essential steps to improving access and outcomes for patients.

OBJECTIVE:Approximately 70 % of patients with epithelial ovarian cancer (EOC) will relapse. Beyond the platinum-free interval (PFI), predictive factors for efficacy of subsequent therapies are poorly understood. We evaluated the impact of the PFI on progression-free survival (PFS), overall survival (OS) and the role of therapies used at relapse. METHODS:This retrospective study using the French ESME Ovarian Database included patients with first relapse of EOC after front-line platinum-based chemotherapy (PBCT). The impact of prognostic factors on survival was analyzed using multivariate Cox regression, with results expressed as hazard ratios, adjusted for patient and tumor characteristics, including a subgroup analysis of high-grade serous cancer. RESULTS:5558 patients, treated between 2010 and 2019 were included (median age 65 IQR 57-71). Median second- and third line PFS and OS were proportionally higher with PFI prolongation. Other factors influencing PFS and OS were BRCA mutation, FIGO stage, chemotherapy and maintenance regimens, and PS. PBCT was more effective than single-agent chemotherapy, even with a PFI < 6 months (PFSn2: adjusted HR = 0.48 95 %IC [0.43;0.53], OSn2: HR = 0.51 95 %IC [0.46;0.57]). Use of PARP inhibitors (PARPi) in second line seems to reduce outcomes in the third line. Findings were consistent in the HGSC subgroup. CONCLUSION:PFI remains an important prognostic factor but should no longer be the sole consideration for treatment selection at relapse in EOC, particularly in HGSC. The potential impact of prior PARPi maintenance on subsequent PBCT warrants investigation in prospective trials.

A laparoscopic approach has been incorporated into the surgical management of a great variety of gynecologic pathologies during the decades following the first description of the method. As knowledge and experience about the use of laparoscopy is accumulating, it is gradually being recognized as an oncologically safe and effective option for the surgical management of various types of gynecological cancer, and the indications for its applications are increasing, as controversial topics are resolved through research. Endometrial cancer is the gynecological malignancy with the most straightforward indications of laparoscopy in its treatment, since a minimally invasive approach is considered the standard of care for both the surgical treatment of early-stage disease and surgical staging through sentinel lymph node biopsy. The role of laparoscopy was significantly decreased in the surgical management of cervical cancer after the publication of the LACC trial which reported worse survival outcomes for patients treated with laparoscopy, and laparotomy has emerged as the preferred approach. However, laparoscopy can be acceptable for carefully selected cases of early-stage cervical cancer and has also been introduced as an effective method for the surgical staging of the disease. The use of laparoscopy in the diagnostic and therapeutic management of ovarian cancer is not fully established but is receiving growing attention, as increasing evidence supports the safety of this approach, especially in the treatment of early-stage disease, where it is considered an acceptable alternative approach to laparotomy. Finally, as laparoscopic advancements are continuously achieved, new indications for laparoscopy have been explored for both vulvar and breast cancer. Future research will identify and highlight new ways to further integrate laparoscopy into the diagnostic and therapeutic management of gynecological malignancies.

BACKGROUND/AIM:The aim of this study was to investigate the efficacy of indocyanine green (ICG) fluorescence angiography in preventing anastomotic leaks and reducing the need for ostomies during cytoreductive surgery in ovarian cancer. PATIENTS AND METHODS:This was a retrospective study of patients with 2014 International Federation of Obstetrics and Gynecology stage IIB-IVB ovarian cancer requiring a bowel resection during primary or secondary cytoreductive surgery at our institution between July 2021 to April 2023. Rates of ostomy performance and anastomotic leak were assessed in the ICG angiography group and the non-ICG angiography group. Frequency distributions between categorical variables were compared using Fisher's exact or Chi-squared test. Wilcoxon rank-sum test and t-test were used to compare continuous variables. RESULTS:During the study period, we reviewed the data of 59 consecutive patients with ovarian cancer with bowel resection; in 30 (50.85%) patients, bowel anastomosis was assessed using ICG angiography and in 29 (49.15%) patients, bowel anastomosis was not assessed using ICG angiography. Anastomotic leak rate was found to be 6.9% (n=2) in the non-ICG angiography group, and 3.33% in the ICG angiography group (n=1) (p=0.612). More diverting ostomies were performed in the non-ICG angiography group (n=6, 20.69%) compared to the ICG angiography group in which no ostomies were performed (p=0.011). CONCLUSION:ICG angiography is not associated with a decrease in anastomotic leak rates, but it may avoid ostomy formation.

BACKGROUND/OBJECTIVES:Cervical cancer (CC) is the fourth most common gynecologic malignancy, disproportionately affecting women in low- and middle-income countries. Despite the effectiveness of HPV vaccination and screening strategies, CC poses a major global health issue, accounting for approximately 94% of annual deaths. Τhis review aims to summarize the current evidence regarding adjuvant treatment indications for surgically treated cervical cancer patients and identify areas where further research is required. METHODS:After a literature search, a comprehensive review of the existing guidelines, clinical trials, and cohort studies related to cervical cancer treatment was conducted, focusing on the role of adjuvant therapy in patients classified as at low, intermediate, and high risk for recurrence, who may require no further treatment. RESULTS:Adjuvant therapy is generally unnecessary for low-risk patients, while high-risk patients with lymph node invasion, parametrial involvement, or large tumor size require chemoradiation (CRT). Ιntermediate-risk patients fall into a grey zone, where the necessity of adjuvant therapy is still debatable. Guidelines emphasize the need for individualization in treatment strategies, since, based on the published studies, careful surgery alone and observation can provide similar outcomes to adjuvant therapy. CONCLUSIONS:This review emphasizes that achieving monotherapy remains pivotal to optimize outcomes and minimize overtreatment. Definitive adjuvant treatment is indicated for high-risk cases, and intermediate-risk patients may benefit from careful observation following adequate surgical intervention, pointing out the necessity of well-designed clinical trials.

(Abstracted from Lancet Oncol 2024;25(12):1551–1562) The leading cause of death due to gynecological cancer is from ovarian cancer. Long-term survival is associated with complete surgical resection and a prolonged platinum-free interval.

Smooth muscle tumors of uncertain malignant potential (STUMP) of the gynecologic tract are a heterogeneous group of tumors, with ambiguous or worrisome features, whose biological behavior is difficult to predict. Several ancillary techniques have been used to try to predict their prognosis, with limited success. This study aimed to explore whether deep learning (DL)-based features can be used to predict progression-free survival (PFS) in STUMP and identify high-risk patients, directly from histological slides. A cohort of 95 STUMP was collected from 7 academic centers (79 for training and 16 for external validation). Nonoverlapping tiles were extracted from the tumor area and used to train a DL model to predict PFS. Python's scikit-learn library and the R software environment were used for data analysis. After 4-fold cross-validation, mean C-indexes of 0.7052 (95% CI, 0.4951-0.9152) and 1.0 (95% CI, 1.0-1.0) were achieved, in the training and external validation cohorts, respectively. The predicted PFS probabilities were used to classify the patients into low-risk and high-risk groups, based on the thresholds of the median and the first quartile of predicted PFS probabilities. Significant differences between both groups were observed, at 10 years, with both thresholds. Cox regression analysis showed that the output of the DL model was associated with a worse prognosis (P = .0356). Both STUMP groups were compared with a cohort of leiomyomas (n = 160) and leiomyosarcomas (n = 58). The lowest hazard ratio was observed in leiomyomas, followed, consecutively, by low-risk STUMP, high-risk STUMP, and leiomyosarcomas. The Cox model showed good discriminatory potential between the 4 groups (all pairwise comparisons were statistically significant). These findings suggest that DL-based features can be used for outcome prediction of STUMP. Additional work is needed to establish whether this "high-risk" group can be identified via molecular markers and used to tailor patient surveillance.