Future of sentinel node biopsy in ovarian cancer.

PURPOSE OF REVIEW: The rationale on the use of sentinel lymph node (SLN) biopsy in the surgical staging of apparent early-stage ovarian cancer (OC) is supported by the fact that diagnostic and prognostic role of systematic staging lymphadenectomy has been determined but its therapeutic significance is still matter of controversy. Moreover, SLN biopsy represents an option to decrease intra- and postoperative morbidity. The present review aims to provide an overview on the current and future role of SLN in OC. RECENT FINDINGS: Most recent evidence shows that the overall mean per patient SLN detection rate in case of indocyanine green (ICG) alone was 58.6% compared with 95% in case of ICG + technetium, and with 52.9% in case of technetium alone or in combination with blue dye ( P  < 0.001). Site of injection has been reported to be in both ovarian ligaments in majority of studies (utero-ovarian ligament and infundibulo-pelvic ligament), before or after ovarian mass removal, at time of primary or re-staging surgery and by minimally invasive or open approach. Cervical injection has been recently proposed to replace utero-ovarian injection. SLN detection rate in patients with confirmed ovarian malignancy varied across different studies ranging between 9.1% and 91.3% for the injection in the utero-ovarian ligament and migration to pelvic lymph nodes and between 27.3% and 100% for the injection in the infundibulo-pelvic ligament and migration to para-aortic lymph nodes. No intra- or postoperative complication could be attributed directly to SLN biopsy. The sensitivity and the accuracy of SLN in detecting lymphatic metastasis ranged between 73.3-100% and 96-100%, respectively. In up to 40% of positive SLNs, largest metastatic deposit was classified as micro-metastasis or isolated tumor cells, which would have been missed without ultrastaging protocol. SUMMARY: SLN biopsy represents a promising tool to assess lymph node status in apparent early-stage OC. The type and volume of injected tracer need to be considered as appear to affect SLN detection rate. Ultrastaging protocol is essential to detect low volume metastasis. Sensitivity and accuracy of SLN biopsy are encouraging, providing tracer injection in both uterine and ovarian ligaments.

Robotic Recto-Sigmoid Resection with Total Intracorporeal Colorectal Anastomosis (TICA) in Recurrent Ovarian Cancer.

BACKGROUND: About 70% of women affected by ovarian cancer experience relapse within 2 years of diagnosis. Traditionally, the standard treatment for recurrent ovarian cancer (ROC) has been represented by systemic chemotherapy.1 Recently, several retrospective studies have suggested that secondary cytoreductive surgery could provide better clinical outcomes than chemotherapy alone, in the case of complete tumor cytoreduction.2,3 About 50% of patients with ROC have a pelvic component of the disease and 22% of patients present isolated pelvic recurrence, often involving the rectum.4,5 Minimally invasive secondary cytoreductive surgery is a feasible option and is associated with favorable perioperative outcomes.6-8 It is crucial to fully explore the peritoneal cavity before starting cytoreductive procedures in order to confirm the absence of carcinomatosis.9 The robotic system facilitates the identification of anatomical structures and makes it easier to perform complex surgical steps in narrow spaces. It also allows the integrated use of surgical tools such as intraoperative ultrasound and indocyanine green application. METHODS: In this video, we present the case of a 64-year-old woman who experienced a rectal recurrence of ovarian cancer after a platinum-free interval of 12 months. We describe, in a step-by-step manner, the surgical procedure of a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis (TICA).10-12 RESULTS: Robotic secondary cytoreduction with complete gross resection was achieved. The patient did not report any intraoperative or postoperative complications. Final histology confirmed ROC. CONCLUSION: Totally robotic rectosigmoid resection is a feasible option in isolated bowel recurrences. Thanks to continuous technical evolution, robot-assisted surgery has the potential to have a central role in the fight against solid tumors. Integration of multiple pre- and intraoperative technologies allows personalized surgery to be performed for each different patient.13,14.

Expanding the Use of HIPEC in Ovarian Cancer at Time of Interval Debulking Surgery to FIGO Stage IV and After 6 Cycles of Neoadjuvant Chemotherapy: A Prospective Analysis on Perioperative and Oncologic Outcomes.

BACKGROUND: Randomized data on patients with FIGO stage III ovarian cancer receiving ≤ 3 cycles of neoadjuvant chemotherapy (NACT) showed that hyperthermic intraperitoneal chemotherapy (HIPEC) after interval debulking surgery (IDS) improved patient's survival. We assessed the perioperative outcomes and PFS of FIGO stage IV and/or patients receiving up to 6 cycles of NACT undergoing IDS+HIPEC. METHODS: Prospectively collected cases from January 1, 2019 to July 31, 2022 were included. Patients underwent HIPEC if: age ≥ 18 years but < 75 years, body mass index ≤ 35 kg/m2, ASA score ≤ 2, FIGO stage III/IV epithelial disease treated with up to 6 cycles of NACT, and residual disease < 2.5 mm. RESULTS: A total of 205 patients were included. No difference was found in baseline characteristics between FIGO Stage III and IV patients, whereas rate of stable disease after NACT (p = 0.004), mean surgical complexity score at IDS (p = 0.001), and bowel resection rate (p = 0.046) were higher in patients undergoing delayed IDS. A lower rate of patients with at least one G3-G5 postoperative complications was observed in FIGO stage IV versus FIGO stage III disease (5.3% vs. 14.0%; p = 0.052). This difference was confirmed at multivariable analysis (odds ratio [OR] 0.24; 95% confidence interval [CI] 0.07-0.80; p = 0.02), whereas age, SCS, bowel resection, and number of cycles did not affect postoperative complications. No difference in PFS was identified neither between FIGO stage III and IV patients (p = 0.44), nor between 3 and 4 versus > 4 cycles of NACT (p = 0.85). CONCLUSIONS: Because of the absence of additional complications and positive survival outcomes, HIPEC administration can be considered in selected FIGO stage IV and patients receiving > 4 cycles of NACT.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) Applied to Platinum-Resistant Recurrence of Ovarian Tumor: A Single-Institution Experience (ID: PARROT Trial).

BACKGROUND: We aimed to investigate the therapeutic efficacy and safety of Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in platinum-resistant recurrence of ovarian cancer and peritoneal carcinomatosis, while our secondary endpoint was to establish any changes in quality of life estimated via the EORTC QLQ-30 and QLQ-OV28 questionnaires. METHODS: In this monocentric, single-arm, phase II trial, women were prospectively recruited and every 28-42 days underwent courses of PIPAC with doxorubicin 2.1 mg/m2 followed by cisplatin 10.5 mg/m2 via sequential laparoscopy. RESULTS: Overall, 98 PIPAC procedures were performed on 43 women from January 2016 to January 2020; three procedures were aborted due to extensive intra-abdominal adhesions. The clinical benefit rate (CBR) was reached in 82% of women. Three cycles of PIPAC were completed in 18 women (45%), and 13 (32.5%) and 9 (22.5%) patients were subjected to one and two cycles, respectively. During two PIPAC procedures, patients experienced an intraoperative intestinal perforation. There were no treatment-related deaths. Nineteen patients showed no response according to the Peritoneal Regression Grading Score (PRGS) and 8 patients showed minor response according to the PRGS. Median time from ovarian cancer relapse to disease progression was 12 months (95% confidence interval [CI] 6.483-17.517), while the median overall survival was 27 months (95% CI 20.337-33.663). The EORTC QLQ-28 and EORTC QLQ-30 scores did not worsen during therapy. CONCLUSIONS: PIPAC seems a feasible approach for the treatment of this subset of patients, without any impact on their quality of life. Since this study had a small sample size and a single-center design, future research is mandatory, such as its application in addition to systemic chemotherapy.

Distribution and prognostic role of BRCA status in elderly ovarian cancer patients.

OBJECTIVE: In the era of target therapy and personalized medicine, BRCA mutational status has a major influence on survival in ovarian cancer patients. Our aim is to verify if the poorer prognosis of elderly ovarian cancer patients can be related to the biology of the tumor beyond their own morbidities and/or suboptimal treatments. METHODS: This is a retrospective single-institution study evaluating prognosis of patients with a diagnosis of ovarian cancer and known BRCA status. We collected clinical and surgical characteristics and the distribution of BRCA mutational status according to age groups. RESULTS: 1840 patients were included in the analysis. The rate of BRCA mutated decreased over age-range from 49.7% in patients aged <50 years to 18.8% in ≥80 years old women. The prognostic role of BRCA status on survival is maintained when focusing on the elderly population, with improved Disease Free Survival (27.2 months vs 16.5 months for BRCA mutated and wild type respectively, p = 0.001) and Cancer Specific Survival (117.6 months vs 43.1 months for BRCA mutated and wild type respectively, p = 0.001) for BRCAmut compared to BRCAwt patients. In the multivariable analysis, among elderly women, upfront surgery and BRCA mutation are independent factors affecting survival. CONCLUSIONS: Elderly patients experiment a poorer prognosis due to multiple factors that include both their medical condition and comorbidities, under-treatment and most importantly disease characteristics. We found that beyond disparities, BRCA mutation is still the strongest independent prognostic factor affecting both the risk of recurrence and death due to disease.

Clinical characteristics and survival outcome of early-stage, high-grade, serous tubo-ovarian carcinoma according to BRCA mutational status.

OBJECTIVE: To investigate the role of BRCA1/2 mutations in early ovarian cancer (eOC) (International Federation of Gynecology and Obstetrics FIGO 2014 stage I-II), and its impact on prognosis after relapse. METHODS: In this multicenter retrospective study, clinical and survival data from high-grade serous (HGS)-eOC patients at presentation and recurrence were compared according to BRCA status: BRCA-mutated (BRCAmut) vs. BRCA wild-type (BRCAwt). RESULTS: Among 191 HGS-eOC patients, 89 were BRCAmut and 102 BRCAwt. There was no significant difference according to the BRCA status in terms of Progression-Free Survival (PFS). A longer Overall Survival (OS) was found in BRCAmut patients. Stage I patients had significantly improved PFS vs stage II, regardless of BRCA status. At multivariate analysis, stage at diagnosis was the only variable with a significant effect on PFS. No factors were significantly relevant on OS, albeit younger age and BRCA mutation showed a slight impact. Post-Recurrence Survival (PRS) in the BRCAmut population was significantly improved compared with BRCAwt. At multivariate analysis, Secondary Cytoreductive Surgery was the strongest predictor for longer PRS, followed by PARPi maintenance at recurrence. CONCLUSIONS: BRCA-status is not a prognostic factor in early ovarian cancer regarding PFS. However, our data suggest a better prognosis after relapse in BRCAm population.

Feasibility and operative outcomes of surgery in the liver area in advanced ovarian cancer.

OBJECTIVE: The study aimed to characterize intra-and postoperative complications according to a standardized anatomo-surgical classification for ovarian cancer metastases in the liver area. METHODS: Data from all patients with advanced ovarian cancer undergoing primary or secondary surgery with perihepatic liver involvement (May-2016 to May-2022), were retrospectively retrieved and classified according to a standardized anatomo-surgical classification, and clustered into four Classes: Class I "Peritoneal", Class II "Hepatoceliac-lymph-nodes", Class III "Parenchymal" and Class IV Mixed (≥ 2 classes). RESULTS: Data from 615 patients were collected. Intraoperative complications were observed in 15%, and severe postoperative complications in 17.6% of cases. While surgical complexity scores were similar, Class IV had longer operative times, higher blood loss, and a 30.4% intraoperative transfusion rate. Class II showed a higher prevalence of vascular injuries (8%). Classes II and IV were significantly associated with severe postoperative complications. Specific complications varied among classes, such as perihepatic collection and intrahepatic hematoma/abscess in Class III (p = 0.003, p < 0.001, respectively), and pleuric effusion, sepsis, anemia, and "other complications" in Class IV (p = 0.002, p = 0.004, p = 0.03, p = 0.03, respectively). Multivariable analysis identified Class II and IV (Class II: OR 4.991, p = 0.045; Class IV: OR 5.331, p = 0.030), Surgical Complexity Score group 3 (OR:3.922, p = 0.003), and the presence of residual tumor (OR:1.748, p = 0.048) as independent risk factors for severe postoperative complications. CONCLUSIONS: Liver procedures during advanced ovarian cancer surgery are feasible with acceptable complication rates According to the anatomo-surgical classification, metastatic patterns are related to both different surgical outcomes and postoperative complication profiles.

The prognosis of stage IA cervical cancer: Subgroup analysis of the SCCAN study.

OBJECTIVE: Patients with TNM T1a cervical cancer have excellent prognosis; however, the risk for recurrence remains an issue of concern and management guidelines are based on limited data. Here we performed subgroup analysis of the Surveillance in Cervical Cancer (SCCAN) consortium with the objective of defining the prognosis of T1a cervical cancer patients. METHODS: SCCAN was an international, multicentric, retrospective cohort study of patients with cervical cancer undergoing surgical treatment in tertiary centers. Inclusion criteria included: histologically confirmed cervical cancer treated between 2007 and 2016; TNM T1a; primary surgical management; and at least 1-year of follow-up data availability. Exclusion criteria included treatment with primary chemo-radiation, and missing treatment-related or clinical data. RESULTS: Out of 975 patients included, 554 (57 %) were T1a1 and 421 (43 %) T1a2. The majority had squamous-cell carcinoma (78 %). 79 patients (8.1 %) had lymphovascular space invasion (LVSI). 455 patients (47 %) underwent radical hysterectomy/ parametrectomy. Laparoscopic and open surgery was performed in 401 (41 %) and in 361 (37 %) patients, respectively. Adjuvant treatment was administered to 56 patients (5.7 %). Assessment of lymph nodes (LN) was performed in 524 patients (54 %), with LN involvement found in 15 (2.9 %). There were 40 (4.1 %) recurrences, occurring at a median of 26 months (4-106), out of which 33 (82.5 %) occurred in pelvis. Among T1a1 cases, there were 10 recurrences (2.0 %) if LVSI was negative, and 3 recurrences (6.7 %) if LVSI was positive. Among T1a2 cases, there were 23 recurrences (6.7 %) if LVSI was negative, and 4 recurrences (5.1 %) if LVSI was positive. There were 3 recurrences in the LN+ group (recurrence rate 20 %). CONCLUSIONS: The risk of recurrence in T1a cervical cancer was 4.1 % corresponding to the rates seen in patients with FIGO 1B cancer in recently published prospective trials. LN involvement represents a risk factor for disease recurrence. Our results indicate that stage T1a cervical cancer, apart from T1a1 LVSI negative disease, should follow the same principles in the management as that of FIGO stage 1B cancer.

Prediction of non-resectability in tubo-ovarian cancer patients using Peritoneal Cancer Index - A prospective multicentric study using imaging (ISAAC study).

BACKGROUND: The aim was to evaluate the performance of the Peritoneal Cancer Index (PCI) using imaging (ultrasound, contrast-enhanced computed tomography (CT), and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI/MRI) in assessing peritoneal carcinomatosis and predicting non-resectability in tubo-ovarian carcinoma patients. METHODS: This was a prospective multicenter observational study. We considered all patients with suspected primary ovarian/tubal/peritoneal cancer who underwent preoperative ultrasound, CT, and WB-DWI/MRI (if available). The optimal cut off value for assessing the performance of the methods in predicting non-resectability was identified at the point at which the sensitivity and specificity were most similar. The reference standard to predict non-resectability was surgical outcome in terms of residual disease >1 cm or surgery not feasible. Agreement between imaging methods and surgical exploration in assessing sites included in the PCI score was evaluated using the Intraclass Correlation Coefficient (ICC). RESULTS: 242 patients were included from January 2020 until November 2022. The optimal PCI cut-off for predicting non-resectability for surgical exploration was >12, which achieved the best AUC of 0.87, followed by ultrasound with a cut-off of >10 and AUC of 0.81, WB-DWI/MRI with a cut-off of >12 and AUC of 0.81, and CT with a cut-off of >11 and AUC of 0.74. Using ICC, ultrasound had very high agreement (0.94) with surgical PCI, while CT and WB-DWI/MRI had high agreement (0.86 and 0.87, respectively). CONCLUSION: Ultrasound performed by an expert operator had the best agreement with surgical findings compared to WB-DWI/MRI and CT in assessing radiological PCI. In predicting non-resectability, ultrasound was non-inferior to CT, while its non-inferiority to WB-DWI/MRI was not demonstrated.

International expert consensus on the surgical anatomic classification of radical hysterectomies.

BACKGROUND: The anatomic descriptions and extents of radical hysterectomy often vary across the literature and operative reports worldwide. The same nomenclature is often used to describe varying procedures, and different nomenclature is often used to describe the same procedure despite the availability of guideline and classification systems. This makes it difficult to interpret retrospective surgical reports, analyze surgical databases, understand technique descriptions, and interpret the findings of surgical studies. OBJECTIVE: In collaboration with international experts in gynecologic oncology, the purpose of this study was to establish a consensus in defining and interpreting the 2017 updated Querleu-Morrow classification of radical hysterectomies. STUDY DESIGN: The anatomic templates of type A, B, and C radical hysterectomy were documented through a set of 13 images taken at the time of cadaver dissection. An online survey related to radical hysterectomy nomenclature and definitions or descriptions of the associated procedures was circulated among international experts in radical hysterectomy. A 3-step modified Delphi method was used to establish consensus. Image legends were amended according to the experts' responses and then redistributed as part of a second round of the survey. Consensus was defined by a yes response to a question concerning a specific image. Anyone who responded no to a question was welcome to comment and provide justification. A final set of images and legends were compiled to anatomically illustrate and define or describe a lateral, ventral, and dorsal excision of the tissues surrounding the cervix. RESULTS: In total, there were 13 questions to review, and 29 experts completed the whole process. Final consensus exceeded 90% for all questions except 1 (86%). Questions with relatively lower consensus rates concerned the definitions of types A and B2 radical hysterectomy, which were the main innovations of the 2017 updated version of the 2008 Querleu-Morrow classification. Questions with the highest consensus rates concerned the definitions of types B1 and C, which are the most frequently performed radical hysterectomies. CONCLUSION: The 2017 version of the Querleu-Morrow classification proved to be a robust tool for defining and describing the extent of radical hysterectomies with a high level of consensus among international experts in gynecologic oncology. Knowledge and implementation of the exact definitions of hysterectomy radicality are imperative in clinical practice and clinical research.

Prediction of nonresectability using the updated Predictive Index value model assessed by imaging and surgery in tubo-ovarian cancer: a prospective multicenter ISAAC study.

BACKGROUND: A laparoscopy-based scoring system was developed by Fagotti et al (Fagotti or Predictive Index value (PIV)score) based on the intraoperative presence or absence of carcinomatosis on predefined sites. Later, the authors updated the PIV score calculated only in the absence of one or both absolute criteria of nonresectability (mesenteric retraction and miliary carcinomatosis of the small bowel) (updated PIV model). OBJECTIVE: The aim was to demonstrate the noninferiority of ultrasound to other imaging methods (contrast enhanced computed tomography (CT) and whole-body diffusion-weighted magnetic resonance imaging (WB-DWI)/MRI) in predicting nonresectable tumor (defined as residual disease >1 cm) using the updated PIV model in patients with tubo-ovarian cancer. The agreement between imaging and intraoperative findings as a reference was also calculated. STUDY DESIGN: This was a European prospective multicenter observational study. We included patients with suspected tubo-ovarian carcinoma who underwent preoperative staging and prediction of nonresectability at ultrasound, CT, WB-DWI/MRI, and surgical exploration. Ultrasound and CT were mandatory index tests, while WB-DWI/MRI was an optional test (non-available in all centers). The predictors of nonresectability were suspicious mesenteric retraction and/or miliary carcinomatosis of the small bowel or if absent, a PIV >8 (updated PIV model). The PIV score ranges from 0 to 12 according to the presence of disease in 6 predefined intra-abdominal sites (great omentum, liver surface, lesser omentum/stomach/spleen, parietal peritoneum, diaphragms, bowel serosa/mesentery). The reference standard was surgical outcome, in terms of residual disease >1 cm, assessed by laparoscopy and/or laparotomy. The area under the receiver operating characteristic curve (AUC) to assess the performance of the methods in predicting nonresectability was reported. Concordance between index tests at the detection of disease at 6 predefined sites and intraoperative exploration as reference standard was also calculated using Cohen's kappa. RESULTS: The study was between 2018 and 2022 in 5 European gynecological oncology centers. Data from 242 patients having both mandatory index tests (ultrasound and CT) were analyzed. 145/242 (59.9%) patients had no macroscopic residual tumor after surgery (R0) (5/145 laparoscopy and 140/145 laparotomy) and 17/242 (7.0%) had residual tumor ≤1 cm (R1) (laparotomy). In 80/242 patients (33.1%), the residual tumor was>1 cm (R2), 30 of them underwent laparotomy and maximum surgery was carried out, and 50/80 underwent laparoscopy only, because cytoreduction was not feasible in all of them. After excluding 18/242 (7.4%) patients operated on but not eligible for extensive surgery, the predictive performance of 3 imaging methods was analyzed in 167 women. The AUCs of all methods in discriminating between resectable and nonresectable tumor was 0.80 for ultrasound, 0.76 for CT, 0.71 for WB-DWI/MRI, and 0.90 for surgical exploration. Ultrasound had the highest agreement (Cohen's kappa ranging from 0.59 to 0.79) than CT and WB-DWI/MRI to assess all parameters included in the updated PIV model. CONCLUSION: Ultrasound showed noninferiority to CT and to WB-DWI/MRI in discriminating between resectable and nonresectable tumor using the updated PIV model. Ultrasound had the best agreement between imaging and intraoperative findings in the assessment of parameters included in the updated PIV model. Ultrasound is an acceptable method to assess abdominal disease and predict nonresectability in patients with tubo-ovarian cancer in the hands of specially trained ultrasound examiners.

Origin of Residual Tumor Masses in BRCA1/2-Driven Ovarian Carcinomas Treated by Neoadjuvant Chemotherapy: Selection of Preexisting BRCA1/2-Proficient Tumor Cells but Not the Gain of Second ORF-Restoring Mutation.

INTRODUCTION: Tubo-ovarian carcinomas (OCs) are highly sensitive to platinum-based neoadjuvant chemotherapy (NACT) but almost never demonstrate complete pathologic response. METHODS: We analyzed paired primary and residual tumor tissues from 30 patients with hereditary BRCA1/2-driven OCs (BRCA1: 17; BRCA2: 13), who were treated by carboplatin/paclitaxel NACT (median number of cycles: 3, range: 3-6). BRCA1/2 and TP53 genes were analyzed by the next-generation sequencing. The ratio between TP53 mutation-specific versus wild-type reads was considered to monitor the proportion of tumor and non-tumor cells in the tissue sample, and the ratio between BRCA1/2-mutated and wild-type reads was used to estimate the presence of cells with the loss or retention of heterozygosity (LOH or ROH, respectively). RESULTS: All 30 OCs had BRCA1/2 LOH in primary tumor and carried somatic TP53 mutation. Twenty-eight OCs had sufficient tumor cell cellularity in the post-NACT tissue to evaluate the ratio between mutated and wild-type BRCA1/2 alleles. Five (18%) out of 28 informative tumor pairs showed transition from LOH to ROH during NACT presumably affecting all or the vast majority of residual tumor cells. There were no signals of the emergence of a second open reading frame-restoring BRCA1/2 mutation. CONCLUSION: Chemonaive BRCA1/2-driven carcinomas may contain a fraction of tumor cells with preserved BRCA1/2 heterozygosity. NACT can cause a selection of pre-existing BRCA1/2-proficient tumor cells, without gaining secondary reversal BRCA1/2 mutations.

New windows of surgical opportunity for gynecological cancers in the era of targeted therapies.

Precision medicine through molecular profiling has taken a prominent role in the treatment of solid tumors and it is widely expected that this will continue to expand. With respect to gynecological cancers, a major change has particularly been observed in the treatment landscape of epithelial ovarian, endometrial, and cervical cancers. Regarding the former, maintenance therapy with either poly(ADP-ribose) polymerase inhibitors (PARPi) and/or bevacizumab has become an indispensable treatment option following the traditional combination of cytoreductive surgery and platinum-based chemotherapy. Considering endometrial cancer, the molecular classification system has now been incorporated into virtually every guideline available and molecular-directed treatment strategies are currently being researched, presumably leading to a further transformation of its treatment paradigm. After all, treatment with immune-checkpoint inhibitors that target the programmed cell death 1 (PD-1) receptor has already been shown to significantly improve disease outcomes in these patients, especially in those with mismatch repair deficient, microsatellite stability-high (MMRd-MSI-H) disease. Similarly, in recurrent/metastatic cervical cancer patients, these agents elicited improved survival rates when being added to platinum-based chemotherapy with or without bevacizumab. Interestingly, implications of these targeted therapies for surgical management have been touched on to a minor extent, but are at least as intriguing. This review therefore aims to address the wide-ranging opportunities the molecular tumor characteristics and their corresponding targeted therapies have to offer for the surgical management of epithelial ovarian, endometrial, and cervical cancers, both in the primary and recurrent setting.

Medicolegal and insurance issues regarding BRCA1 and BRCA2 gene tests in high income countries.

Hereditary breast and ovarian cancer syndrome is an autosomal dominant cancer susceptibility syndrome mainly due to variants in BRCA1 or BRCA2 genes. Patients presenting with BRCA1 or BRCA2 gene mutations have a lifetime risk of developing breast or ovarian cancer (80% and 40%, respectively). Genetic testing to explore the predisposition to develop cancer represents a pivotal factor in such cases, and this review wants to explore the main implications in terms of medicolegal liability and insurance issues. Medicolegal issues related to these diagnostic processes include: (a) failure to recommend the test; (b) failure to properly interpret the test; (c) failure to correctly translate results into clinical practice; (d) lack of informed consent; and (e) failure to refer patients to specialized genetic counseling. Such errors may lead to compensation since the legal burden inherent in the efficacy of prophylactic interventions is a proof that requires the so-called 'preponderance of the evidence'. Concerning insurance issues, the carriers of such alleles without cancer are healthy because the genetic predisposition is not a disease per se but represents a (relevant) health risk. However, disclosure of these conditions can be impelled by insurers. It can lead to so-called 'genetic discrimination' because insurance companies might use genetic information to limit insurance options or increase their costs. Many private and public healthcare funders do not cover risk reducing surgeries, even when recommended as part of a risk reduction management plan for BRCA gene mutation carriers. Here, positions on these matters from different high income countries are discussed, stressing the importance of a common supranational or international regulatory framework to reach a trade-off between the economic interests of insurers and the rights of carriers not to disclose extremely sensitive information.

Early non-compliance to ERAS in gynecological open surgery for malignancies, and post-operative complications: a multicenter, prospective, observational, cohort study.

BACKGROUND: Open surgical procedures for gynecological malignancies have a potential risk of post-operative complications and hence prolonged hospitalization, despite adherence to an Enhanced Recovery After Surgery (ERAS) protocol. PRIMARY OBJECTIVE: To investigate the relationship between non-compliance to an ERAS protocol in the post-operative setting and the rate of post-operative complications, in women who underwent open surgery for gynecological malignancies. STUDY HYPOTHESIS: Early non-compliance with the ERAS protocol increases the risk of post-operative complications. TRIAL DESIGN: Multicenter, prospective, observational, cohort study. MAJOR INCLUSION CRITERIA: Patients with histologically proven gynecological cancer (endometrial, uterine, tubo-ovarian, and cervical) undergoing elective open surgery and managed according to ERAS guidelines. EXCLUSION CRITERIA: Patients with post-operative recovery in an intensive care unit, undergoing anterior or total pelvic exenteration or intraperitoneal chemotherapy. Previous radiotherapy or previous non-gynecological major abdominal surgery. PRIMARY ENDPOINT: Association of non-compliance with the ERAS protocol using five selected indicators on post-operative day 2 with the rate of 30-day post-operative complications. SAMPLE SIZE: 600 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: At present, 106 patients have been recruited. Based on this, the accrual should be completed in 2025. Results should be presented at the end of 2025. TRIAL REGISTRATION: NCT05738902.

Assessing minimally invasive simple hysterectomy in low risk cervical cancer: set up for the LASH trial.

After the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, open surgery has become the standard approach for radical hysterectomy in early stage cervical cancer. Recent studies assessed the role of a non-radical approach in low risk cervical cancer and showed no survival difference compared with radical hysterectomy. However, there is a gap in knowledge regarding the oncologic outcomes of minimally invasive simple hysterectomy in low risk cervical cancer. This review offers an overview of the current evidence on the role of the minimally invasive approach in low risk cervical cancer and raises the need for a new clinical trial in this setting.

Effects of niraparib dose reduction on short-term outcomes in ovarian cancer patients.

OBJECTIVES: Despite the individualized starting dose for maintenance therapy in ovarian cancer, the niraparib dose reduction rate remains high. The aim of this study was to evaluate the impact of niraparib dose reduction on progression-free survival in newly diagnosed primary advanced ovarian cancer and recurrent ovarian cancer patients. We also aimed to compare the reduction rates and the safety of niraparib on primary and relapse groups, and identify which factors may predict dose reduction. METHODS: Patients with primary or recurrent ovarian cancer in maintenance who received niraparib between 2019 and 2022 were retrospectively evaluated. Niraparib dosing was based on individualized starting dose of 300 or 200 mg/day. The impact of niraparib dose reductions was focused on patients treated with 200 or 100 mg in both groups. Reduction rates, adverse events and predictive factors of reduction were assessed in each study group. The primary endpoint was progression-free survival in primary and relapse groups; the secondary endpoints were the reduction rates, the safety and tolerability of niraparib in both groups. RESULTS: Of 215 patients identified, 124 (57.7%) primary and 91 (42.3%) recurrent ovarian cancer patients were included. The majority of patients started niraparib at 200 mg/day (92.7% primary and 80.2% relapse group); dose reductions from 300 or 200 mg/day to 200 or 100 mg/day occurred more frequently within cycles 1-3 (67% primary and 45% relapse group, p=0.001). Grade≥3 adverse events were lower in the relapse group (54.8% primary and 35.1% relapse, p=0.001). In both groups, dose modifications over the treatment did not significantly impair median progression-free survival. Univariate and multivariate analysis demonstrated that weight and platinum-doublets were possible risk factors for dose reduction. CONCLUSIONS: Niraparib dose reduction occurs in almost half of patients within cycles 1-3, although it is significantly more common in the first-line setting. Survival outcomes seem not to be impaired by dose reduction.

ESGE/ESGO/SERGS consensus statement on surgical steps in minimally invasive surgery in gynecologic oncology: transperitoneal and extraperitioneal approach for paraaortic lymphadenectomy.

INTRODUCTION: Assessment of retroperitoneal nodes is an important part of the surgical staging of gynecologic cancers. Although pelvic and paraaortic lymphadenectomy have been widely described by different authors, there is little consensus on the description of the different surgical steps for each procedure. An Intergroup Committee on Onco-Gyn Minimally Invasive Surgery has been established with members of the European Society for Gynecological Endoscopy (ESGE), European Society of Gynaecological Oncology (ESGO) and the Society of European Robotic Gynaecological Surgery (SERGS). The Intergroup Committee has various objectives: writing down a surgical description of the technique, which will be assessed by a group of experts following a formal consensus method and developing a specific Objective Structured Assessment of Technical Skills (OSATS) scale for each procedure. METHODS: A hierarchical task analysis was conducted by a working group of eight experts from the three societies in order to identify the surgical steps of transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy. The selection of the definitive surgical steps was confirmed by a group of 19 experts from the different societies, following a formal consensus method. Two rounds of Delphi panel rating were considered necessary for achieving an agreement. The consensus agreement identified 29 surgical steps in transperitoneal and 17 surgical steps in extraperitoneal approach to complete a paraaortic lymphadenectomy. Once the description of the procedure and the consensus were established, an Objective specific Scale for the Assessment of Technical Skills for Paraaortic lymphadenectomy (PA-OSATS) in the transperitoneal and extraperitoneal approach was developed. RESULTS: In the first round of rating we found that 28 steps out of 29 in the transperitoneal approach and 13 out of 17 in the extraperitoneal approach did not reach a strong degree of agreement. They were reformulated based on comments made by the experts, and submitted to a second round of rating and this finally achieved an agreement. CONCLUSION: We defined a list of surgical steps in transperitoneal and extraperitoneal approach in paraaortic lymphadenectomy and a specific PA-OSATS scale for these procedures. This tool will be useful for teaching, assessing and standardizing this surgical procedure.

Robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese).

BACKGROUND: Nearly 65% of patients with endometrial cancer who undergo primary hysterectomy have concurrent obesity. Retrospective data show advantages in using robotic surgery in these patients compared with conventional laparoscopy, namely lower conversion rate, increased rate of same-day discharge, and reduced blood loss. Nevertheless, to date no prospective randomized controlled trials have compared laparoscopic surgery versus robotic-assisted surgery in morbidly obese patients. PRIMARY OBJECTIVE: The robotic-assisted versus conventional laparoscopic surgery in the management of obese patients with early endometrial cancer in the sentinel lymph node era: a randomized controlled study (RObese) trial aims to find the most appropriate minimally invasive surgical approach in morbidly obese patients with endometrial carcinoma. STUDY HYPOTHESIS: Robotic surgery will reduce conversions to laparotomy in endometrial cancer patients with obesity compared with those who undergo surgery with conventional laparoscopy. TRIAL DESIGN: This phase III multi-institutional study will randomize consecutive obese women with apparent early-stage endometrial cancer to either laparoscopic or robot-assisted surgery. MAJOR INCLUSION/EXCLUSION RITERIA: The RObese trial will include obese (BMI≥30 kg/m2) patients aged over 18 years with apparent 2009 Federation of Gynecology and Obstetrics (FIGO) stage IA-IB endometriod endometrial cancer. PRIMARY ENDPOINT: Conversion rate to laparotomy between laparoscopic surgery versus robot-assisted surgery. SAMPLE SIZE: RObese is a superiority trial. The clinical superiority margin for this study is defined as a difference in conversion rate of -6%. Assuming a significance level of 0.05 and a power of 80%, the study plans to randomize 566 patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Patient recruitment will be completed by 2026, and follow-up will be completed by 2029 with presentation of data shortly thereafter. Two interim analyses are planned: one after the first 188 and the second after 376 randomized patients. TRIAL REGISTRATION: NCT05974995.

Obesity paradox: is a high body mass index positively influencing survival outcomes in gynecological cancers? A systematic review and meta-analysis.

OBJECTIVE: Obesity represents an exponentially growing preventable disease leading to different health complications, particularly when associated with cancer. In recent years, however, an 'obesity paradox' has been hypothesized where obese individuals affected by cancer counterintuitively show better survival rates. The aim of this systematic review and meta-analysis is to assess whether the prognosis in gynecological malignancies is positively influenced by obesity. METHODS: This study adheres to PRISMA guidelines and is registered with PROSPERO. Studies reporting the impact of a body mass index (BMI) of >30 kg/m2 compared with <30 kg/m2 in patients with gynecological cancers listed in PubMed, Google Scholar and ClinicalTrials.gov were included in the analysis. The Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2) was used for quality assessment of the selected articles. RESULTS: Twenty-one studies were identified for the meta-analysis, including 14 108 patients with cervical, ovarian, or endometrial cancer. There was no benefit in 5-year overall survival for obese patients compared with non-obese patients (OR 1.2, 95% CI 1.00 to 1.44, p=0.05; I2=71%). When pooling for cancer sub-groups, there were no statistically significant differences in 5-year overall survival in patients with cervical cancer and 5-year overall survival and progression-free survival in patients with ovarian cancer. For obese women diagnosed with endometrial cancer, a significant decrease of 44% in 5-year overall survival (p=0.01) was found, with no significant difference in 5-year disease-free survival (p=0.78). CONCLUSION: According to the results of the present meta-analysis, a BMI of ≥30 kg/m2 does not have a positive prognostic effect on survival compared with a BMI of <30 kg/m2 in women diagnosed with gynecological cancers. The existence of the 'obesity paradox' in other fields, however, suggests the importance of further investigations with prospective studies.