Objective To investigate whether neoadjuvant chemotherapy followed by interval debulking surgery is superior to primary debulking surgery in terms of perioperative complications and progression-free survival, in advanced epithelial ovarian, fallopian tube or primary peritoneal cancer patients with high tumor load. Methods Patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (stage IIIC-IV) underwent laparoscopy. Patients with high tumor load assessed by a standardized laparoscopic predictive index were randomly assigned (1:1 ratio) to undergo either primary debulking surgery followed by adjuvant chemotherapy (arm A), or neoadjuvant chemotherapy followed by interval debulking surgery and adjuvant chemotherapy (arm B). Co-primary outcome measures were progression-free survival and post-operative complications; secondary outcomes were overall survival, and quality of life. Survival analyses were performed on an intention-to-treat population. Results 171 patients were randomly assigned to primary debulking surgery (n=84) versus neoadjuvant chemotherapy (n=87). Rates of complete resection (R0) were different between the arms (47.6% in arm A vs 77.0% in arm B; p=0.001). 53 major postoperative complications were registered, mainly distributed in arm A compared with arm B (25.9% vs 7.6%; p=0.0001). All patients were included in the intent-to-treat analysis. With an overall median follow-up of 59 months (95% CI 53 to 64), 142 (83.0%) disease progressions/recurrences and 103 deaths (60.2%) occurred. Median progression-free and overall survival were 15 and 41 months for patients assigned to primary debulking surgery, compared with 14 and 43 months for patients assigned to neoadjuvant chemotherapy, respectively (HR 1.05, 95% CI 0.77 to 1.44, p=0.73; HR 1.12, 95% CI 0.76 to 1.65, p=0.56). Conclusions Neoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities, but the toxicity profile is different.

Recently, the new 2023 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer (EC) critically integrating new pathological and molecular features was published. The present study evaluated the clinical impact of the new 2023 FIGO staging system by comparing it to the previous 2009 system. This is an international, pooled retrospective study of 519 EC patients who underwent primary treatment (and molecular characterisation) at three European Society of Gynaecological Oncology (ESGO) accredited centres in Austria/Italy. Patients were categorised according to the 2009 and the 2023 FIGO staging systems. Stage shifts were analysed and (sub)stage specific 5-year progression-free (PFS) and overall survival (OS) rates were calculated and compared. Different statistical tests were applied to evaluate the prognostic precision of the two FIGO staging systems and to compare them to each other. (Sub)stage shifts occurred in 143/519 (27.6%) patients: 123 upshifts (23.7%) and 20 (3.9%) downshifts. 2023 FIGO staging system identified a stage I cohort with a notably higher 5-year PFS rate compared to 2009 (93.0% versus 87.4%, respectively). For stage II disease, the 5-year PFS rate was similar in the 2023 and the 2009 FIGO staging systems (70.2% versus 71.2%, respectively). The two new molecularly defined 2023 FIGO substages IAm_POLEmut and IICm_p53abn displayed distinct, particularly favourable and adverse oncologic outcomes within early stage disease, respectively. A remarkably lower 5-year PFS rate for stage III patients was revealed in the 2023 FIGO staging system compared to 2009 (44.4% versus 54.1%, respectively). All applied statistical tests confirmed a more accurate prediction of PFS and OS by the 2023 FIGO staging system compared to 2009. The new 2023 FIGO stating system led to a substantial stage shift in about one quarter of patients leading to a higher prognostic precision. In early stage disease, the new substages added further prognostic granularity and identified treatment relevant subgroups.

Several genes associated with hereditary ovarian cancer have been discovered as a result of the work done with next generation sequencing. It is estimated that approximately 23% of ovarian carcinomas have a hereditary predisposition. The most common hereditary condition is represented by germline mutations in BRCA1 or BRCA2 genes that account for 20–25% of high grade serous ovarian cancer. A number of other hereditary ovarian cancers are associated with different genes, with a crucial role in the DNA damage response pathway, such as the mismatch repair genes in Lynch syndrome, TP53 in Li-Fraumeni syndrome, STK11 in Peutz-Jeghers syndrome, CHEK2, RAD51, BRIP1, and PALB2. The goal of this manuscript is to summarize the published data regarding the molecular pathways involved in the pathogenesis of non-BRCA related hereditary ovarian cancer and to provide a tool that might be useful in discussing risk assessment, genetic testing, prevention strategies, as well as clinical and therapeutic implications for patients with ovarian cancer.

Background Observational studies have supported the practice of offering minimally invasive interval debulking surgery after neoadjuvant chemotherapy for well-selected patients with advanced epithelial ovarian cancer. However, there are no prospective randomized data comparing the oncologic efficacy of minimally invasive and open interval debulking surgery in epithelial ovarian cancer. Primary objective The primary objective of this study is to examine whether minimally invasive surgery is non-inferior to laparotomy in terms of disease-free survival in women with advanced stage epithelial ovarian cancer that responded to three or four cycles of neoadjuvant chemotherapy. Study hypothesis We hypothesize that in patients who had a complete or partial response to neoadjuvant chemotherapy, minimally invasive interval debulking surgery is not inferior to laparotomy. Trial design The Laparoscopic cytoreduction After Neoadjuvant ChEmotherapy (LANCE) trial is an international, prospective, randomized, multicenter, non-inferiority phase III trial to compare minimally invasive surgery vs laparotomy in women with advanced stage high-grade epithelial ovarian cancer that had a complete or partial response to three or four cycles of neoadjuvant chemotherapy and normalization of CA-125. The first 100 participants will be enrolled into a pilot lead-in to determine feasibility. The study will be considered feasible and will continue to Phase III under the following conditions: the accrual rate reaches at least 80% of the target rate after all pilot sites are open; the crossover rate in the minimally invasive group is less than 25%; and the difference of complete gross resection between the minimally invasive and open group is less than 20%. If the study is determined to be feasible, all remaining participants will be enrolled into the Phase III stage. Major inclusion/exclusion criteria Patients with stage IIIC or IV high-grade epithelial ovarian, primary peritoneal or fallopian tube carcinoma who had a complete or partial response to three or four cycles of neoadjuvant chemotherapy based on imaging and normalization of CA-125 will be enrolled. Patients with evidence of tumor not amenable to minimally invasive resection on pre-operative imaging will be excluded. Primary endpoint The primary endpoint is non-inferiority of disease-free survival in minimally invasive vs laparotomic interval debulking surgery. Sample size To demonstrate non-inferiority with a margin of 33% in the hazard ratio (HR=1.33), 549 patients will be randomized.

Purpose: Build predictive radiomic models for early relapse and BRCA mutation based on a multicentric database of high-grade serous ovarian cancer (HGSOC) and validate them in a test set coming from different institutions. Methods: Preoperative CTs of patients with HGSOC treated at four referral centers were retrospectively acquired and manually segmented. Hand-crafted features and deep radiomics features were extracted respectively by dedicated software (MODDICOM) and a dedicated convolutional neural network (CNN). Features were selected with and without prior harmonization (ComBat harmonization), and models were built using different machine learning algorithms, including clinical variables. Results: We included 218 patients. Radiomic models showed low performance in predicting both BRCA mutation (AUC in test set between 0.46 and 0.59) and 1-year relapse (AUC in test set between 0.46 and 0.56); deep learning models demonstrated similar results (AUC in the test of 0.48 for BRCA and 0.50 for relapse). The inclusion of clinical variables improved the performance of the radiomic models to predict BRCA mutation (AUC in the test set of 0.74). Conclusions: In our multicentric dataset, representative of a real-life clinical scenario, we could not find a good radiomic predicting model for PFS and BRCA mutational status, with both traditional radiomics and deep learning, but the combination of clinical and radiomic models improved model performance for the prediction of BRCA mutation. These findings highlight the need for standardization through the whole radiomic pipelines and robust multicentric external validations of results.

Cervical cancer continues to have a significant incidence, despite global efforts in HPV vaccination campaigns. Managing this condition involves a diverse team of healthcare professionals. Research in this field is undergoing a period of great revolution in multiple areas, and international guidelines will soon have to adapt to new scientific evidence. This could be true mainly in locally advanced stages, and it could also be true for minimal invasive surgery. This paper aims to summarize and compare the most recent recommendations published by international gynecological oncological societies for patients with cervical cancer. From their comparison, common aspects and disagreements emerged, especially in the diagnostic pathway and follow-up strategies. Several issues that remain to be debated in the literature were addressed and compared, highlighting similarities and differences, from the role of the sentinel lymph node in early stages to that of the adjuvant hysterectomy in locally advanced tumors. On the surgical side, for this last subset of patients, currently, a laparotomic approach is recommended. At the same time, the advent of immunotherapy has just opened up new and promising scenarios in systemic treatment for locally advanced cervical cancer, and international guidelines will soon introduce it into their algorithms.