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.

OBJECTIVE:This study aimed to assess the prognostic impact of celiac lymph node involvement in patients with advanced high-grade serous ovarian cancer. METHODS:We conducted a retrospective, single-center study including patients who underwent celiac lymph node resection during either upfront or interval complete cytoreductive surgery as frontline treatment for advanced high-grade serous ovarian cancer between January 2002 and December 2022. Patients were categorized into 2 groups based on celiac lymph node status. Univariable and multi-variable analyses were performed, and survival rates were estimated using the Kaplan-Meier method. RESULTS:Among 820 patients who underwent cytoreductive surgery for ovarian cancer during the study period, 65 (7.9%) had celiac lymph node resection and were included. Celiac lymph node metastases were identified in 42 (64.6%) cases. Celiac lymph node-positive patients had a higher tumor burden (p =.001), more frequent bowel involvement (p =.026), and higher rates of left hemicolectomy (17.1% vs 0.0%) and inguinal lymphadenectomy (16.7% vs 0.0%). Median overall survival was 30.9 months in the celiac lymph node-positive group and 50.6 months in the celiac lymph node-negative group (p =.270); median disease-free survival was 10.8 and 14.6 months (p =.082), respectively. In multi-variable analysis, celiac lymph node involvement was significantly associated with decreased disease-free survival (hazard ratio 2.87 [1.38 to 5.93], p =.005). CONCLUSIONS:Celiac lymph node involvement is associated with a higher tumor burden and significantly associated with a decrease in disease-free survival in cases of advanced high-grade serous ovarian cancer. These results highlight the need to identify celiac lymph node involvement for better risk stratification.

PURPOSE:Platinum-based chemotherapy and surgery are pivotal in managing ovarian cancer (OC), yet prognosis remains poor, and early biomarkers for platinum resistance are needed. The neoadjuvant setting provides an opportunity to evaluate tumor responsiveness to platinum chemotherapy in vivo. This study evaluated whether early measures of platinum response combined with molecular alterations could predict surgical outcomes and survival in patients with OC treated with neoadjuvant chemotherapy (NACT). METHODS:The CHIVA study enrolled stage III/IV OC patients eligible for three cycles NACT with or without nintedanib, followed by interval debulking surgery. Archival samples underwent extensive sequencing to detect clinically relevant variants and copy number alterations and calculate genomic instability (GIS). Early chemotherapy response measures-cancer antigen 125 kinetics by KELIM, major pathologic response, GIS status, tumor infiltrating lymphocytes (TILs) abundance, and genomic alterations-were correlated with surgery completeness and survival. RESULTS:Among 127 patients, the overall response rate was 44%, and the complete cytoreduction (CC0) rate was 54.8%. Homologous recombination deficiency (HRD) was identified in 56% of patients and was associated with better survival. The median progression-free survival was 21.4, 20.5, and 14.4 months in the BRCAmut, BRCAwt/GIS-high, and BRCAwt/GIS-low subgroups, respectively (P = .001). Unfavorable KELIM predicted lower objective response rate, CC0, and shorter survival, while low intraepithelial TILs (ieTILs) correlated with poor outcomes. Multivariate analysis confirmed KELIM, HRD status, and ieTILs as independent biomarkers. CCNE1 amplifications, observed in 20% of patients, were associated with moderate chemotherapy sensitivity. CONCLUSION:HRD status, KELIM, and TILs are key independent biomarkers in advanced OC. CCNE1 amplifications, although typically associated with platinum resistance, were linked to moderate chemotherapy sensitivity, defining an intermediate prognostic subgroup.

High-grade serous ovarian cancer (HGSOC) remains a leading cause of gynecological cancer mortality, with only <15% of patients achieving long-term, relapse-free survival. Using data from the VIVROVAIRE (NCT03418844) and CHIVA (NCT03418844) clinical trials, this study investigated the molecular and immunophenotypic characteristics of long-term recurrence-free survivors (LTS) compared with short-term survivors (STS). Tumor samples from 37 LTS (recurrence-free ≥3 years) and 105 STS were analyzed using next-generation sequencing, BRCA1/RAD51C promoter methylation assays, shallow whole genome and multiplex immunofluorescence. Homologous recombination deficiency (HRD) was defined by BRCA1/2 or RAD51C/D alterations, and genomic instability scores (GIS). Immune profiling included quantification of CD4+, CD8+, CD20+, and FOXP3+ cells. LTS were younger and had a lower prevalence of FIGO stage IV disease. Molecularly, LTS showed fewer TP53 mutations, enrichment of BRCA2 mutations and BRCA1 and RAD51C promoter methylation, and a strong association between RB1 loss co-occurring with a BRCA alteration. Conversely, CCNE1 amplification was underrepresented in LTS. Immune profiling demonstrated increased stromal and intraepithelial CD8+ T-cell infiltration and reduced FOXP3+ regulatory T cells in LTS. Overall, exceptional survival in HGSOC is associated with younger age, enrichment of BRCA2 mutations and BRCA1/RAD51C methylation, reduced CCNE1 amplification, and a competent antitumor immune response. These findings highlight potential biomarkers for refining risk stratification and guiding personalized therapeutic strategies in ovarian cancer management.

Complete macroscopic resection is the key objective of cytoreductive surgery for peritoneal malignancy. However, heterogeneity in terminology and operative technique persists across centres and between surgical and gynaecological disciplines. This study sought to establish international consensus on the nomenclature of cytoreductive surgery procedures, key technical principles of peritonectomy procedures and visceral resections, and management of regional lymph nodes in the context of peritoneal malignancy. A modified Delphi process was undertaken involving 148 surgical and gynaecological oncologists across six continents. Cytoreductive surgery was endorsed as the preferred term for potentially curative surgery for peritoneal malignancy. Agreement was reached on core principles guiding peritonectomy, including the extent of peritoneal resection around tumour deposits. For visceral resections, the panel favoured a conservative, tumour biology-informed strategy that considers disease distribution and patient-specific factors. The group recommended selective removal of clinically enlarged nodes only. This global consensus defines foundational principles for cytoreductive surgery in patients with peritoneal malignancy and provides standardised terminology and operative guidance that can be integrated into routine surgical practice across various surgical oncology disciplines. Adoption of these recommendations has the potential to reduce variability in cytoreductive surgery techniques, facilitate comparison between studies by increasing standardisation, and facilitate the design and conduct of high-quality surgical trials in peritoneal malignancy.

5505 Background: In patients treated for advanced ovarian cancer not suitable for complete primary surgery, interval surgery after three courses of neoadjuvant chemotherapy (NAC) has been considered standard management since the EORTC randomized trial published in 2010 (NCT00003636, DOI: 10.1056/NEJMoa090880). Delaying surgery after six courses of NAC in highly chemosensitive patients amenable to complete surgery after 3 cycles remains controversial. CHRONO is a multicenter, randomized phase II trial addressing this question (NCT03579394). Methods: Patients treated for a stage IIIB-IVA high grade epithelial ovarian cancer by NAC and amenable to complete surgery after 3 cycles were randomized (1:1) to either complete surgery followed by 5 cycles of chemotherapy (control arm: C) or an additional 3 cycles of NAC followed by complete surgery then 2 cycles of chemotherapy (experimental arm: E). Maintenance treatment was administered according to standard of care. Primary endpoint was disease free survival (DFS) defined as the time from randomization until the date of disease progression or second cancer or death from any cause. The study was designed to detect an improvement in median (m) DFS from 10 months to 17 months (HR=0.59) with a 85% power and 2-sided α=0.05. Main secondary endpoints were Pathological complete response (CC0) rate, post operative morbidity and mortality, quality of life (QOL) and overall survival (OS). Results: Between 18/10/2018 and 23/04/2024, 209 patients (median age: 69 years) were randomized to arm C (n=103) or E (n=106). Median total number of cycles of NAC was 7 (5-9) and 8 (3-9) in arm C and E .CC0 rate was 83.2% vs 90%. After a median follow up of 40.4 months, mDFS was 20.2 months (95%CI: 18.2-23.6) in arm C vs 23.4 (19.0-30.4) in arm E (Log-rank test p=0.48, HR: 0.88 (95%CI: 0.63-1.24). The longitudinal analysis of QoL found no significant differences between the two arms, however, social functioning, insomnia, and sexuality showed a trend toward further improvement (≥5 points) in arm E. Major postoperative complication rates within 30 days were 5% and 11% in arm C and E, (p=0.11) , with no death within 30 days after surgery. Conclusions: CHRONO is the first randomized trial addressing the clinical impact of delayed surgery after 6 courses of NAC in first line treatment of advanced ovarian cancer. No statistically significant difference was shown between the two arms of the study considering DFS, severe morbidity, mortality or QoL. New trials are needed for a better understanding of this alternative to interval surgery in highly chemosensitive advanced ovarian cancer patients. Clinical trial information: NCT03579394 .