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PurposeThe purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma.MethodsThis multicenter, retrospective observational cohort study included patients with FIGO 2009 stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case–control matching was used to adjust the baseline characteristics.ResultsA total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (p = 0.542 and p = 0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (p < 0.001) and had a better 5-year disease-free survival (DFS) than patients who did not receive conization (89.8% vs. 80.0%, respectively; p = 0.010). No difference in 5-year overall survival (OS) (97.1% vs. 91.4%, respectively; p = 0.114) or recurrence pattern (p = 0.115) was reported between the two groups. Factors independently related to higher risk of recurrence were pathologic tumor diameter >20 mm and no conization before radical hysterectomy (p = 0.011 and p = 0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (p = 0.020).ConclusionsConization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.

A European consensus conference on endometrial carcinoma was held in 2014 to produce multidisciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy & Oncology (ESTRO) and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide. ESGO/ESTRO/ESP nominated an international multidisciplinary development group consisting of practicing clinicians and researchers who have demonstrated leadership and expertise in the care and research of endometrial carcinoma (27 experts across Europe). To ensure that the guidelines are evidence-based, the literature published since 2014, identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the development group. The guidelines are thus based on the best available evidence and expert agreement. Prior to publication, the guidelines were reviewed by 191 independent international practitioners in cancer care delivery and patient representatives. The guidelines comprehensively cover endometrial carcinoma staging, definition of prognostic risk groups integrating molecular markers, pre- and intra-operative work-up, fertility preservation, management for early, advanced, metastatic, and recurrent disease and palliative treatment. Principles of radiotherapy and pathological evaluation are also defined.

BackgroundPhase 3 randomized clinical trials have been designed to compare secondary cytoreductive surgery followed by systemic therapy with systemic therapy alone for management of patients with recurrent ovarian cancer. This study aimed to compare differences in clinical outcomes between these two treatment approaches.MethodsThe PRISMA statement was applied. Only phase 3 randomized clinical trials were included in the final analysis.ResultsThree randomized clinical trials (n = 1250 patients) were identified. Secondary cytoreductive surgery was associated with significantly better progression-free survival (PFS) improvement than systemic therapy alone (hazard ratio [HR], 95% CI, 0.61–0.78; p < 0.001). The PFS benefit was greater for the complete resection subpopulation (HR, 0.56; 95% CI, 0.48–0.66; p < 0.001). The HR of overall survival (OS) was similar between the groups (HR, 0.93; 95% CI, 0.78–1.10; p = 0.37), but it was 0.73 (95% CI, 0.59–0.91) in favor of the complete resection subpopulation.ConclusionThis meta-analysis showed secondary cytoreductive surgery as superior to systemic therapy alone in terms of PFS. The PFS and OS benefits were particularly observed for complete surgical resection. The impact on OS in the general population remains to be proven.

BackgroundRecently, it was reported that minimally invasive surgery (MIS) has a negative impact on early-stage cervical cancer (ECC) patient survival. At the same time, advantages of MIS regarding quality of life and low rate of intra- and postoperative complications are well known. Therefore, it is essential to select patients who may benefit from MIS without worsening their oncologic outcomes. The aim of this study is to investigate which pathological factors could guide surgeons’ choice about the best approach in ECC.Patients and MethodsPatients with 2009 FIGO stage from IA1 with lymphovascular space invasion (LVSI) to IB1/IIA1 treated by open or laparoscopic surgery were judged eligible for the study. Disease-free survivals (DFS) of both approaches were tested in subgroups, defined according to histology, tumor size, grading, LVSI, parametrial involvement, and nodal status.ResultsA total of 423 patients were enrolled (217 in the open and 206 in the laparoscopic group). No difference between open surgery and laparoscopy was found among subgroups defined according to histology, grading, LVSI, parametrial involvement, or nodal status. Among patients with tumor > 20 mm, laparoscopy showed a significantly higher relapse risk [hazard ratio (HR): 2.103, p = 0.030]. Among patients with tumor < 20 mm, laparoscopy showed DFS superimposable to open surgery (HR: 0.560, p = 0.128).ConclusionsTumor size of 20 mm appeared as the only independent discrimination criterion in patients whose prognosis is affected by surgical approaches.

PurposeReporting the perioperative and survival outcomes of vaginectomy with respect to a matched series of pelvic exenteration (PE) in women with isolated recurrent cervical cancer.MethodsThe records of vaginal recurrent cervical cancer patients admitted at Fondazione Policlinico “Agostino Gemelli” IRCCS in Rome from January 2010 to June 2019 were retrospectively analyzed. A propensity-matched score analysis was performed by age, clinical stage, disease-free interval, and R0 resection. Postsurgical complications and survival rates were evaluated.ResultsFifteen women underwent vaginectomy, and 30 patients were submitted to PE. No statistical differences were observed between the two groups at baseline characteristics. The vaginectomy procedures were successfully performed in all women, and no case required conversion to PE. Moreover, a higher rate of major postoperative complications after PE with respect to vaginectomy (p = 0.027) was recorded. Among them, three women required reoperation within 30 postoperative days, and four experienced two or more complications. Twenty-five (55.6%) women experienced recurrence: 8 of 25 (32.0%) in the vaginectomy group, and 17 of 25 (68%) in the PE group, with a median progression-free survival of 20 months and 13 months, respectively (p = 0.169). In total, 5 of 15 (33.3%) died of disease in the vaginectomy group and 13/30 (43.3%) in the PE group, with a median overall survival of 39 and 18 months for vaginectomy and PE, respectively (p = 0.161).ConclusionsThe vaginectomy seems to allow for salvage treatment, such as radiotherapy and/or PE, but with a minimal impact on the quality of life in appropriately selected women with local recurrent cervical cancer.

BackgroundFew 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.MethodsRetrospective, 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. ResultsThree 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.ConclusionSII ≥ 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.

Radiogenomics is a specific application of radiomics where imaging features are linked to genomic profiles. We aim to develop a radiogenomics model based on ovarian US images for predicting germline BRCA1/2 gene status in women with healthy ovaries. From January 2013 to December 2017 a total of 255 patients addressed to germline BRCA1/2 testing and pelvic US documenting normal ovaries, were retrospectively included. Feature selection for univariate analysis was carried out via correlation analysis. Multivariable analysis for classification of germline BRCA1/2 status was then carried out via logistic regression, support vector machine, ensemble of decision trees and automated machine learning pipelines. Data were split into a training (75%) and a testing (25%) set. The four strategies obtained a similar performance in terms of accuracy on the testing set (from 0.54 of logistic regression to 0.64 of the auto-machine learning pipeline). Data coming from one of the tested US machine showed generally higher performances, particularly with the auto-machine learning pipeline (testing set specificity 0.87, negative predictive value 0.73, accuracy value 0.72 and 0.79 on training set). The study shows that a radiogenomics model on machine learning techniques is feasible and potentially useful for predicting g BRCA1/2 status in women with healthy ovaries.

ObjectiveThe aim of this study was to assess the correlation between BRCA mutation status and disease presentation, treatment strategy, and survival in a multicenter series of recurrent high-grade serous ovarian cancer (HGSOC) women.MethodsA consecutive series of recurrent HGSOC patients with partially or fully platinum-sensitive disease admitted to the Gynecologic Oncology Units of the Catholic University of the Sacred Heart and Sapienza University of Rome. Main eligibility criteria were known BRCA 1/2 germline mutation status and a minimum follow-up period from recurrence of at least 6 months.ResultsOverall, 126 patients met the eligibility criteria, of whom 76 (60%) were BRCA wild-type (BRCAwt) and 50 (40%) were BRCA 1/2 germline mutation carriers (BRCAmut). Among the latter, 37 (74%) patients presented with BRCA1 mutation, and 13 (26%) presented with BRCA2. No differences were found regarding patterns of disease presentation between BRCAwt and BRCAmut women. BRCAmut patients had the best post-recurrence survival (PRS) regardless of having received secondary cytoreductive surgery (SCS) or not, with a 5-year PRS of 73% in non-resected women versus 78% in resected women (p = 0.558). Conversely, BRCAwt patients who underwent complete SCS had a significantly longer PRS compared with BRCAwt patients who did not receive surgery (5-year PRS of 54% vs. 42%; p = 0.048).ConclusionsRecurrent ovarian cancer BRCAmut patients have the best prognosis regardless of SCS, whereas PRS in BRCAwt women can improve when complete SCS is performed. The identification and incorporation of predictive biomarkers such as BRCA status to tailor the medical and surgical approach is paramount to the success of recurrent HGSOC treatments.

BackgroundAdditional prognostic factors and personalized therapeutic alternatives for vulvar squamous cell carcinoma (VSCC), especially for advanced stages with poor prognosis, are urgently needed.ObjectivesTo review and assess literature regarding underlying molecular mechanisms of VSCC target therapeutic and prognostic approaches.MethodsWe performed a narrative literature review from the inception of the database up to January 2020 limited to English language, organizing knowledge in five main fields: extracellular and intracellular cell cycle deregulation, tumor immune microenvironment, tumor angiogenesis and hormones.ResultsEGFR immunohistochemical overexpression/gene amplification, representing early events in VSCC carcinogenesis, have been correlated with a worse prognosis and led to inclusion of erlotinib in cancer guidelines. p16 expression and HPV positivity are linked to a better prognosis, while p53 overexpression is linked to a worse prognosis; thus, biomarkers could help tailoring conventional treatment and follow-up. The implications of PD-L1 positivity in reference to HPV status and prognosis are still not clear, even though pembrolizumab is part of available systemic therapies. The role of tumor angiogenesis emerges through data on microvessel density, immunohistochemical VEGF staining and evaluation of serum VEGF concentrations. Few data exist on hormonal receptor expression, even though hormonal therapy showed great manageability.ConclusionsWe suggest adding p16, p53 and HPV status to routine hystopathological examination of vulvar biopsies or surgical specimens. Predictive biomarkers for anti-EGFR and anti-PD-1/PD-L1 drugs are needed. Enough preclinical data supporting anti-angiogenic target therapies in clinical trials are existing. Hormonal receptor expression deserves further investigation.