Domenico Ferraioli

Is total mesorectal excision mandatory in advanced ovarian cancer patients undergoing posterior pelvic exenteration? Prognostic role of mesorectal space involvement in a prospective ovarian cancer cohort

In advanced epithelial ovarian cancer (AEOC), debulking surgery with posterior pelvic exenteration (PPE) is performed in 35-70 % of the patients to achieve no macroscopic residual disease. This study aims to evaluate the incidence of mesorectal involvement and its prognostic role in AEOC patients undergoing PPE. This prospective study analyzes data from a cohort of AEOC patients who underwent primary debulking surgery (PDS) or interval debulking surgery (IDS) with PPE at the Léon Bérard Cancer Center in Lyon between 2018 and 2022. 73 patients underwent debulking surgery with PPE during the study period. 27 (34 %) underwent PPE during PDS and 46 (66 %) during IDS. 23 patients (31.5 %) had only serosal involvement, 19 (26 %) had bowel involvement up to the muscularis propria, and 7 (9.6 %) had up to the mucosa. Mesorectal involvement was observed in 40 cases (54.7 %) and was significantly associated with positive MLNs and higher liver recurrence rates. Hepatic metastases had an early onset (months, 9.8 vs 28.8; p = 0.0001) and were correlated with poorer OS (months, 20.9 vs 51.5) compared to recurrences in other sites. The persistence of positive mesorectum after neoadjuvant chemotherapy in the IDS group seemed to be linked to poor OS (NR vs 42.7 months). Debulking surgery with PPE in AEOC patients is often needed. Total mesorectal excision should be performed in AEOC to achieve no residual disease because positive mesorectum after neoadjuvant chemotherapy seemed to be linked with poor OS, with early onset and increased incidence of liver metastasis.

Primary ovarian leiomyosarcoma: results from an analysis by the French Sarcoma Group (Ovarian SArcoma MAnagement – OSAMA Study)

Primary ovarian leiomyosarcomas are exceptionally rare, constituting less than 1% of ovarian tumors, and they typically have a poor prognosis. The available data on the management of these tumors are sparse, with limited publications mainly comprising small retrospective series that include multiple histologic types. The aim is to evaluate the clinical, surgical, pathologic characteristics and clinical outcome of patient affected by primary ovarian leiomyosarcomas. Using the national database (NetSarc), we conducted a retrospective study of the outcomes of primary ovarian leiomyosarcomas at 18 French Sarcoma Group centers. Patients with any International Federation of Gynecology and Obstetrics stage of primary ovarian leiomyosarcoma at first diagnosis and available follow-up were included. A total of 39 patients with primary ovarian leiomyosarcomas were included: 35 had localized disease and 4 had metastatic disease. The median tumor size was 134 mm. Radical and wide surgery was performed on 21 (62%) and 13 patients (38%), respectively. Tumor grade 3, presence of necrosis, mitoses ≥20 high-power field, and high Ki-67 expression >30% were reported in 17 of 34 (50%), 29 of 34 (85%), 17 of 34 (50%), and 17 of 27 patients (63%), respectively. Positive estrogen receptor expression was reported in 14 of 27 patients (52%), whereas progesterone receptor expression was observed in 10 of 27 patients (37%). Adjuvant chemotherapy was administered in 12 of 34 patients (35%), whereas pelvic adjuvant radiotherapy in 8 of 34 (23%). Of the early-stage primary ovarian leiomyosarcomas, 9 had isolated pelvic recurrence, whereas 18 had parenchymal distant metastases. A total of 15 patients (44%) died of disease. In early-stage primary ovarian leiomyosarcomas, high mitotic counts and progesterone receptor negativity were variables associated with worse survival. Surgery is the cornerstone of treatment for early-stage primary ovarian leiomyosarcoma, whereas the role of adjuvant treatment remains unclear. Some pathologic features were associated with poorer survival. Owing to the rarity of ovarian leiomyosarcomas, referring patients to expert sarcoma centers is highly recommended.

Ovarian clear cell carcinoma: open questions on the management and treatment algorithm

Abstract Ovarian clear cell carcinoma (OCCC) accounts for ~10% of all epithelial ovarian cancers and is considered a different entity from the more common high-grade serous ovarian carcinoma (HGSC), with distinct clinical presentations, different risk, and prognostic factors, and specific molecular features. Most OCCCs are diagnosed at an early stage and show favorable outcomes, in contrast to those diagnosed at advanced stages, which exhibit intrinsic resistance to platinum-based chemotherapy regimens and a very poor prognosis. The standard treatment of advanced OCCC is currently based on primary debulking surgery followed by platinum-based chemotherapy according to recent international guidelines. However, these recommendations are extrapolated from several trials mainly featuring a large cohort of HGSC, with only a small minority of OCCC. Because of its rarity, many questions remain unanswered regarding the surgical and medical treatment. Lymph node staging, fertility-sparing treatment, the use of targeted therapies and radiotherapy as well as the adjuvant treatment for early-stage disease and second or further lines of chemotherapy are still under debate. This review aims to address these unresolved issues, by providing a comprehensive overview of the current data on this disease, and to suggest possible directions for future research.

Immune landscape and potential role of immune checkpoint inhibitors on uterine leiomyosarcoma: a review

Uterine leiomyosarcoma is a rare and aggressive malignancy with limited therapeutic options and poor prognostic outcomes. Immune checkpoint inhibitors have transformed oncology; however, their efficacy in leiomyosarcoma remains uncertain. This review explores the immunological landscape of uterine leiomyosarcoma, focusing on the role of checkpoint blockade and potential strategies to optimize treatment. The tumor microenvironment plays a crucial role in shaping immune responses, with leiomyosarcomas often exhibiting variable programmed death-ligand 1 expression, differential lymphocytic infiltration, and interactions with tumor-associated macrophages. Despite modest response rates in clinical trials, molecular analyses suggest that specific sub-groups may derive greater benefit from checkpoint inhibition. Moreover, dual-checkpoint blockade combining anti-programmed death-1 and anti-cytotoxic T-lymphocyte-associated antigen-4 agents has demonstrated enhanced immune activation in select patients. In addition, chemotherapy-induced immunogenic cell death has been explored as a complementary approach to immunotherapy. These findings support the need for innovative combinatorial strategies aimed at augmenting immune responsiveness in leiomyosarcoma. The integration of checkpoint inhibitors with targeted immunomodulation and personalized therapeutic approaches may improve treatment efficacy. Future research should focus on refining patient selection criteria, enhancing macrophage-targeted therapies, and optimizing immune profiling techniques to maximize therapeutic outcomes for uterine leiomyosarcoma.

Splenectomy in epithelial ovarian cancer surgery

Splenectomy is performed in 4-32% of cytoreductive surgeries for ovarian cancer. The objective of our study was to assess splenectomy and evaluate its impact on overall and disease-free survival. We conducted a retrospective single-center study between January 2000 and December 2016. Patients who underwent a cytoreduction for epithelial ovarian cancer, regardless of stage and surgical approach, were eligible for the study. Patients deemed not operable were excluded from the study. Patients were stratified into two groups, splenectomy or no splenectomy. A univariate analysis followed by a multivariate analysis was conducted to evaluate the postoperative complications after splenectomy and the overall and disease-free survival. This cohort included 464 patients. Disease stages, peritoneal carcinomatosis scores, and the rate of radical surgery (Pomel classification) were significantly higher in the splenectomy group, p=0.04, p<0.0001, and p<0.001, respectively. However, no significant difference was found in the rate of complete cytoreduction between the two groups (p=0.26) after multivariate analysis. In univariate analysis, splenectomy was significantly associated with extensive surgical procedures. In multivariate analysis, the two more prevalent complications in the splenectomy group were the risk of abdominopelvic lymphocele (overall response (OR) =4.2; p=0.01) and blood transfusion (OR=2.4; p=0.008). The average length of hospital stay was significantly longer in the splenectomy group, 17.4 vs 14.6 days (p<0.0001). The delay in adjuvant chemotherapy was longer in the splenectomy group (p=0.001). There was no significant difference in overall and disease-free survival (p=0.09) and (p=0.79), respectively. Splenectomy may be considered an acceptable and safe procedure; however, with no impact on overall or disease-free survival. In addition, it is associated with longer hospital stay and longer time to chemotherapy.

Impact of multidisciplinary tumour board in the management of ovarian carcinoma in the first‐line setting. Exhaustive analysis from the Rhone‐Alpes region

Epithelial ovarian cancer (EOC) is a poor prognosis disease partly linked to diagnosis at an advanced stage. The quality of care management is a factor that needs to be explored, more specifically optimal organisation of first-line treatment. A retrospective study, dealing with all patients diagnosed within the Rhone-Alpes region with initial diagnosis EOC in 2012, was performed. The aim was to describe the impact of multidisciplinary tumour boards (MTB) in the organisation of care and the consequence on the patient's outcomes. 271 EOC were analysed. 206 patients had an advanced EOC. Median progression-free survival (PFS) is 17.8 months (CI95%, 14.6-21.2) for AOC. 157 patients (57.9%) had a front-line surgery versus 114 patients (42.1%) interval debulking surgery. PFS for AOC patients with no residual disease is 24.3 months compared with 15.3 months for patients with residual disease (p = .01). No macroscopic residual disease is more frequent in the patients discussed before surgery in MTB compared with patients not submitted before surgery (73% vs. 56.2%, p < .001). These results highlight the heterogeneity of medical practices in terms of front-line surgery versus interval surgery, in the administration of neoadjuvant chemotherapy and in the setting of MTB discussion.