Alexandre de Nonneville

Endometrioid ovarian carcinoma landscape: pathological and molecular characterization

Endometrioid ovarian cancers (EOvC) are usually managed as serous tumors. In this study, we conducted a comprehensive molecular investigation to uncover the distinct biological characteristics of EOvC. This retrospective multicenter study involved patients from three European centers. We collected clinical data and formalin‐fixed paraffin‐embedded (FFPE) samples for analysis at the DNA level using panel‐based next‐generation sequencing and array‐comparative genomic hybridization. Additionally, we examined mRNA expression using NanoString nCounter® and protein expression through tissue microarray. We compared EOvC with other ovarian subtypes and uterine endometrioid tumors. Furthermore, we assessed the impact of molecular alterations on patient outcomes, including progression‐free survival (PFS) and overall survival (OS). Preliminary analysis of clinical data from 668 patients, including 86 (12.9%) EOvC, revealed more favorable prognosis for EOvC compared with serous ovarian carcinoma (5‐year OS of 60% versus 45%; P  = 0.001) driven by diagnosis at an earlier stage. Immunohistochemistry and copy number alteration (CNA) profiles of 43 cases with clinical data and FFPE samples available indicated that EOvC protein expression and CNA profiles were more similar to endometrioid endometrial tumors than to serous ovarian carcinomas. EOvC exhibited specific alterations, such as lower rates of PTEN loss, mutations in DNA repair genes, and P53 abnormalities. Survival analysis showed that patients with tumors harboring loss of PTEN expression had worse outcomes (median PFS 19.6 months vs. not reached; P  = 0.034). Gene expression profile analysis confirmed that EOvC differed from serous tumors. However, comparison to other rare subtypes of ovarian cancer suggested that the EOvC transcriptomic profile was close to that of ovarian clear cell carcinoma. Downregulation of genes involved in the PI3K pathway and DNA methylation was observed in EOvC. In conclusion, EOvC represents a distinct biological entity and should be regarded as such in the development of specific clinical approaches.

Posterior pelvic exenteration for ovarian cancer: surgical and oncological outcomes

Posterior pelvic exenteration (PPE) can be required to achieve complete resection in ovarian cancer (OC) patients with large pelvic disease. This study aimed to analyze morbidity, complete resection rate, and survival of PPE. Ninety patients who underwent PPE in our Comprehensive Cancer Center between January 2010 and February 2021 were retrospectively identified. To analyze practice evolution, 2 periods were determined: P1 from 2010 to 2017 and P2 from 2018 to 2021. A 82.2% complete resection rate after PPE was obtained, with rectal anastomosis in 96.7% of patients. Complication rate was at 30% (grade 3 in 9 patients), without significant difference according to periods or quality of resection. In a binary logistic regression adjusted on age and stoma, only age of 51-74 years old was associated with a lower rate of complication (odds ratio=0.223; p=0.026). Median overall and disease-free survivals (OS and DFS) from initial diagnosis were 75.21 and 29.84 months, respectively. A negative impact on OS and DFS was observed in case of incomplete resection, and on DFS in case of final cytoreductive surgery (FCS: after ≥6 chemotherapy cycles). Age ≥75-years had a negative impact on DFS for new OC surgery. For patients with complete resection, OS and DFS were decreased in case of interval cytoreductive surgery and FCS in comparison with primary cytoreductive surgery. PPE is an effective surgical measure to achieve complete resection for a majority of patients. High rate of colorectal anastomosis was achieved without any mortality, with acceptable morbidity and high protective stoma rate.