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ObjectiveTo evaluate the role of different specific types of germline breast cancer susceptibility BRCA mutations on the age of onset of high grade serous ovarian cancer. MethodsThis was a multicenter, international, retrospective cohort of 474 patients diagnosed with recurrent or newly diagnosed high grade serous ovarian cancer, with known germline mutations in BRCA1/2 genes, treated between January 2011 and December 2020 in three academic centers in Europe. Patients were classified into four groups related to the type of BRCA1/2 genes mutation: frameshift, missense, nonsense, and splicing. Data from patients with splicing mutations were removed from the analysis because of the small numbers. The other three groups were compared. ResultsExcluding the 29 patients with a splicing mutation, 474 patients were enrolled: 309 (65.2%) with frameshift mutations, 102 (21.5%) with nonsense mutations, and 63 (13.3%) with missense mutations. The BRCA1 gene was affected in 324 (68.4%) cases, while BRCA2 was involved in 150 (31.6%) women (p=0.06). We found a difference of more than 5 years in the age of onset of high grade serous ovarian cancer between BRCA1 and BRCA2 patients (mean 53.3 years vs 58.4 years; p=0.001), with a mean age of 55.1 years. Patients with nonsense germline mutations had the youngest age of onset, while women with frameshift mutations had the oldest age of onset of high grade serous ovarian cancer (mean 52.2 years vs mean 55.9 years), both in the BRCA1 and BRCA2 subgroups. There was no statistically significant difference in age of onset between early and advanced groups (mean 55.8 years vs 55.0 years; p=0.55). ConclusionDifferent types of germline BRCA mutations could determine different ages for onset of high grade serous ovarian cancer. If confirmed in larger series, this finding might have a clinical impact, potentially leading to a more tailored approach for risk reducing surgery for the prevention of high grade serous ovarian cancer.

Background: Few studies analyzed the prognostic role of systemic inflammatory markers in early-stage ovarian cancer. The primary endpoint of the present study was to assess the prognostic impact of baseline inflammatory markers in early-stage ovarian cancer. The secondary endpoints were to compare the disease-free survival (DFS) of inflammatory markers with standard risk factors and to correlate these with BRCA mutational status. Methods: Retrospective, single-center, observational study. Patients with FIGO-stage I-II and IIIA1 epithelial ovarian cancer undergoing primary surgery between 10/2012 and 12/2019 were included. Inflammatory markers were evaluated on the results of the complete blood count and coagulation tests, performed before ovarian cancer surgery. The Receiver Operating Characteristic curve was used to determine the optimal cut-off value of different baseline inflammatory biomarkers for the DFS analysis. Results: Three hundred fifty-nine patients were included in the study period. Baseline neutrophil-lymphocyte ratio (NLR) ≥ 3 and systemic immune inflammation index (SII, defined as platelet x neutrophil-lymphocyte ratio) ≥ 1000 were associated with worse 3 year DFS and baseline SII ≥ 1000 was associated with worse 3 year OS. BRCA-mutated patients with SII ≥ 1000 and with NLR ≥ 3 had significantly worse DFS compared to SII < 1000 and with NLR < 3. FIGO stage > I was the only independent risk factor for higher risk of recurrence. Conclusion: SII ≥ 1000 and NLR ≥ 3 were associated with worse 3 year DFS and SII ≥ 1000 was associated with worse 3 year OS. The subgroups of BRCA-mutated patients with higher inflammation markers (SII ≥ 1000 and NLR ≥ 3) were associated with worse DFS. These findings might be helpful to design personalized treatment and more intensive surveillance.

Background and Objective: This study aims to investigate the surgical outcomes observed in robotic transperitoneal aortic lymphadenectomy (AL) in gynecological cancer patients. Methods: Retrospective data were collected and analyzed on 71 patients undergoing robotic surgical procedures for gynecological cancers, including transperitoneal AL, between December 2014 and February 2018 at the Catholic University of the Sacred Heart, Rome, Italy. Results: Median age of the sample population was 50 years (range, 26-76 years). The median operative time was 210 minutes (range, 75-480 minutes), the median estimated blood loss was 50 ml (range, 20-300 ml). The number of para-aortic nodes removed was 12 (range, 7-43). In the whole series, 13 patients (18.3%) had at least one metastatic node. Overall, 10 patients (14.1%) experienced any grade early postoperative complications. Three patients experienced more than one complication. Three intraoperative complications occurred with two cases of vascular injury. Conversion to laparotomy was necessary for one patient (1.4%). Conclusions: The present study shows the safety and adequacy of robotic transperitoneal AL as surgical staging step for gynecological cancers in terms of perioperative and postoperative outcomes.

Objectives: To compare survival outcomes and peri-operative complications in patients with advanced ovarian cancer with 1–10 mm residual disease (RD) at primary debulking surgery (PDS) versus those achieving no gross residual disease (NGR) at interval debulking surgery (IDS). Methods: Patients operated with the intent of complete cytoreduction for epithelial ovarian/fallopian tube/primary peritoneal cancer, FIGO stage IIIC-IV, RD 1–10 mm at PDS and NGR at IDS, between 01/2010 and 12/2016, were retrospectively included. All patients had at least 2-years of follow-up completed. Results: 207 patients were included (59 PDS and 148 IDS). Patients in PDS group were younger and had a higher surgical complexity score. There was a higher rate of intra- and major early post-operative complications in the group of PDS vs IDS (16.9% vs 1.3% and 28.8% vs 2.0%, p < 0.0001 respectively). After a median follow up of 56.4 months (range 59.2–65.4), 117 (56.5%) patients died of disease in the whole population. Forty-eight (81.4%) patients had progression/recurrent disease in the PDS group and 120 (81.1%) in the IDS group. Median PFS was 16.2 months and 18.9 months for PDS and IDS group, respectively (p = 0.111). Median OS was 41.4 months and 52.4 months for PDS and IDS group, respectively (p = 0.022). Conclusions: IDS should be considered the preferred treatment in case millimetric residual disease is expected at PDS in view of the superimposable PFS and the reduced number of perioperative complications.

Background: This study aims at evaluating the feasibility, surgical outcome and oncological results observed after robotic radical hysterectomy (RH) compared to laparoscopy for patients with early stage cervical cancer (ECC) patients. Methods: Between January 2010 and October 2016, 210 patients underwent RH for treatment of ECC: 70 underwent robotic approach (Cases), and 140 underwent laparoscopic approach (Controls). Results: There was no statistically significant difference between the two approaches with regard to clinical patient characteristics and in terms of extent of RH and rate of pelvic and aortic lymphadenectomy. Operative time was significantly longer in the robotic versus laparoscopic group (median = 243 min, range 90–612 versus median = 210 min, range 80–660; p value = 0.008). Conversion to laparotomy was necessary in 4 patients (1.9%) in the whole series. No difference was found in terms of intraoperative and postoperative complications between the two groups. Overall, during the observation period, 34 (16.2%) patients experienced any grade postoperative complications, and 21 (10.0%) had >G2 complications. The 3-yr DFS was 88.0% versus 84.0% in robotic and laparoscopic group, respectively (p value = 0.866). Central and/or lateral pelvic disease represented the most common site of relapse. The 3-yr OS was 90.8% in patients underwent robotic RH versus 94.0% in patients underwent laparoscopic RH (p value = 0.924). Conclusions: The present study shows the equivalence of robotic and laparoscopic approaches to radical surgery of ECC patients, in terms of perioperative and postoperative outcomes with equivalent survival figures, and thus the choice of approach can be tailored to the choice of patient and surgeon.

Study Objective: To demonstrate management of a rare case of an isolated intraparenchymal splenic metastasis of endometrial cancer with robotic-assisted surgery. Design: Case report (Canadian Task Force Classification III). Setting: A 55-year-old patient with a history of endometrial cancer was found to have a splenic lesion on a follow-up examination. She underwent surgical staging, involving total hysterectomy, bilateral salpingo-oopherectomy, pelvic lymphadenectomy, and peritoneal washing, in 2014, and the final pathological findings showed an endometrioid endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics stage IB G2. Multidisciplinary counseling was provided, and the patient opted for strict medical surveillance. At 20 months after the primary treatment, the patient experienced a vaginal cuff recurrence and refused radiation therapy. She instead underwent robotic surgery, followed by 6 cycles of carboplatin 6 AUC and paclitaxel 175 mg/m2. Seventeen months later, a positron emission tomography/computed tomography scan revealed a 3-cm intraparenchymal lesion of the spleen, and robotic splenectomy was scheduled. The Institutional Review Board approved this study. Intervention: The operative time was 90 minutes, and blood loss was <50 mL. The operation was performed successfully, with no intraoperative and postoperative complications. Histopathological analysis showed a 3-cm intraparenchymal splenic lesion. The patient was discharged on day +2, and 46 days later started adjuvant chemotherapy based on carboplatin 6 AUC and doxorubicin (Caelyx) 30 mg/m2. At a 2-month follow-up, the patient was disease-free and in good general condition. Conclusion: This case demonstrates the successful robotic management of recurrent endometrial cancer.

ObjectiveTo evaluate the role of different specific types of germline breast cancer susceptibility BRCA mutations on the age of onset of high grade serous ovarian cancer. MethodsThis was a multicenter, international, retrospective cohort of 474 patients diagnosed with recurrent or newly diagnosed high grade serous ovarian cancer, with known germline mutations in BRCA1/2 genes, treated between January 2011 and December 2020 in three academic centers in Europe. Patients were classified into four groups related to the type of BRCA1/2 genes mutation: frameshift, missense, nonsense, and splicing. Data from patients with splicing mutations were removed from the analysis because of the small numbers. The other three groups were compared. ResultsExcluding the 29 patients with a splicing mutation, 474 patients were enrolled: 309 (65.2%) with frameshift mutations, 102 (21.5%) with nonsense mutations, and 63 (13.3%) with missense mutations. The BRCA1 gene was affected in 324 (68.4%) cases, while BRCA2 was involved in 150 (31.6%) women (p=0.06). We found a difference of more than 5 years in the age of onset of high grade serous ovarian cancer between BRCA1 and BRCA2 patients (mean 53.3 years vs 58.4 years; p=0.001), with a mean age of 55.1 years. Patients with nonsense germline mutations had the youngest age of onset, while women with frameshift mutations had the oldest age of onset of high grade serous ovarian cancer (mean 52.2 years vs mean 55.9 years), both in the BRCA1 and BRCA2 subgroups. There was no statistically significant difference in age of onset between early and advanced groups (mean 55.8 years vs 55.0 years; p=0.55). ConclusionDifferent types of germline BRCA mutations could determine different ages for onset of high grade serous ovarian cancer. If confirmed in larger series, this finding might have a clinical impact, potentially leading to a more tailored approach for risk reducing surgery for the prevention of high grade serous ovarian cancer.