Raffaella Ergasti

Failure of early interval debulking surgery after standard neoadjuvant chemotherapy: May bevacizumab add something? A large retrospective study

Data are limited on the use of bevacizumab in neoadjuvant setting for High-Grade Serous ovarian Cancer (HGSC) patients. This study explores the effect of adding bevacizumab to standard neoadjuvant chemotherapy (NACT) following the failure of early Interval Debulking Surgery (eIDS). This monocentric study retrospectively enrolled FIGO stage IIIC-IV HGSC patients (2017-2021), persisting unresectable after three NACT cycles. Eligible patients had an ECOG performance status ≤2, were aged 40-75 years, and had no contraindications to bevacizumab administration. Patients were stratified whether they added bevacizumab from cycles 4 to 6 (CPB group) or not (CP group). The primary endpoint was the cytoreduction rate after six cycles (delayed IDS, dIDS). Overall, 58(23 %) patients received neoadjuvant bevacizumab(CPB), and 190 (77 %) did not (CP). Delayed IDS was performed in 117(47.6 %) patients (CPB:31-53.4 %; CP:86-45.8 %; p = 0.38), with complete gross resection rates of 83.9 % and 88.5 %, respectively (p = 0.72). Severe postoperative complications were comparable (CP: 8 %, CPB: 9.7 %, p = 0.069). Median overall survival (OS) for dIDS patients showed no significant difference (CPB: not reached, CP:38 months, p = 0.55), nor did progression-free survival (PFS; CPB:14 months, CP:12 months, p = 0.830). Conversely, among 130(52 %) patients persisting unresectable, bevacizumab significantly improved OS in the CPB group (not reached vs.18 months, p = 0.015), although PFS remained similar (CPB: 6 months, CP: 7 months, p = 0.741). While adding bevacizumab to NACT does not seem to increase the dIDS rate, it significantly extends OS in unresectable patients. Its use may be a valuable option in selected cases after eIDS' failure.

Risk reducing surgery with peritoneal staging in BRCA1-2 mutation carriers. A prospective study

International guidelines recommend risk-reducing salpingo-oophorectomy (RRSO) in BRCA1-2 mutations carriers to decrease ovarian cancer occurrence. In this prospective study, we describe the incidence of occult malignancies and the surgical outcomes in asymptomatic BRCA mutation carriers submitted to RRSO. Data on BRCA1-2 carriers undergoing RRSO with peritoneal washing and peritoneal/omental biopsies (PeS), between January 2019 until March 2021, were prospectively collected. A total of 132 patients were enrolled: 74 BRCA1 and 58 BRCA2 mutation carriers. 31.1% women underwent RRSO and PeS (16.2% of BRCA1 and 50% of BRCA2 carriers), while 68.9% patients were submitted also to concomitant hysterectomy. Almost all the procedures (99.2%) were performed by minimally invasive surgery. Postoperative complications occurred in twelve patients (9.1%): 10 in the concomitant hysterectomy group and two complications in the RRSO group. At the final pathological examination, 6 (4.5%) occult carcinomas were diagnosed: 3 fallopian tube carcinomas, one ovarian carcinoma and two serous tubal intraepithelial carcinomas (STICs), with negative PeS. Median age of occult carcinomas patients at RRSO was 54 (range: 48-79) years. The mean follow up was 20 (range: 7-34) months. During the follow up, no primary peritoneal cancer has been diagnosed. Occult pathologic findings in RRSO occurred in 4.5% (3% invasive carcinomas, STIC 1.5%) among our patients. The routine use of peritoneal biopsies does not improve the detection of occult malignancies. Our data confirm the importance of timely performing RRSO in BRCA1-2 carriers.

Lymph node staging in grade 1–2 endometrioid ovarian carcinoma apparently confined to the ovary: Is it worth?

The aim of this study was to assess the disease-free survival (DFS) and overall survival (OS) of patients with grade 1-2 endometrioid ovarian carcinoma apparently confined to the ovary, according to surgical staging. Multicenter, retrospective, observational cohort study. Patients with endometrioid ovarian carcinoma, surgical procedure performed between May 1985 and December 2019, stage pT1 N0/N1/Nx, grade 1-2 were included. Patients were stratified according to lymphadenectomy (defined as removal of any lymph node versus no lymph node assessment), and subgroup analyses according to tumor grade were performed. Kaplan-Meier curves and cox regression analyses were used to perform survival analyses. 298 patients were included. 199 (66.8 %) patients underwent lymph node assessment. Of these, 166 (83.4 %) had unilateral/bilateral pelvic and para-aortic/caval lymphadenectomy. Eleven (5.5 %) patients of those who underwent lymph node assessment showed pathologic metastatic lymph nodes (FIGO stage IIIA1). Twenty-seven patients (9.1 %) had synchronous endometrioid endometrial cancer. After a median follow up of 45 months (95 %CI:37.5-52.5), 5-year DFS and OS of the entire cohort were 89.8 % and 96.2 %, respectively. Age ≤ 51 years (HR=0.24, 95 %CI:0.06-0.91; p = 0.036) and performance of lymphadenectomy (HR=0.25, 95 %CI: 0.07-0.82; p = 0.022) represented independent protective factors toward risk of death. Patients undergoing lymphadenectomy had better 5-year DFS and OS compared to those not receiving lymphadenectomy, 92.0 % versus 85.6 % (p = 0.016) and 97.7 % versus 92.8 % (p = 0.013), respectively. This result was confirmed after exclusion of node-positive patients. When stratifying according to tumor grade (node-positive excluded), patients with grade 2 who underwent lymphadenectomy had better 5-year DFS and OS than those without lymphadenectomy (93.0 % versus 83.1 %, p = 0.040 % and 96.5 % versus 90.6 %, p = 0.037, respectively). Staging lymphadenectomy in grade 2 endometrioid ovarian carcinoma patients was associated with improved DFS and OS. Grade 1 and grade 2 might be considered as two different entities, which could benefit from different approach in terms of surgical staging. Prospective studies, including molecular profiles are needed to confirm the survival drivers in this rare setting.