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Late diagnosis and the lack of screening methods for early detection define high-grade serous ovarian cancer (HGSOC) as the gynecological malignancy with the highest mortality rate. In the work presented here, we investigated a retrospective and multicentric cohort of 250 archival Papanicolaou (Pap) test smears collected during routine gynecological screening. Samples were taken at different time points (from 1 month to 13.5 years before diagnosis) from 113 presymptomatic women who were subsequently diagnosed with HGSOC (pre-HGSOC) and from 77 healthy women. Genome instability was detected through low-pass whole-genome sequencing of DNA derived from Pap test samples in terms of copy number profile abnormality (CPA). CPA values of DNA extracted from Pap test samples from pre-HGSOC women were substantially higher than those in samples from healthy women. Consistently with the longitudinal analysis of clonal pathogenic TP53 mutations, this assay could detect HGSOC presence up to 9 years before diagnosis. This finding confirms the continual shedding of tumor cells from fimbriae toward the endocervical canal, suggesting a new path for the early diagnosis of HGSOC. We integrated the CPA score into the EVA (early ovarian cancer) test, the sensitivity of which was 75% (95% CI, 64.97 to 85.79), the specificity 96% (95% CI, 88.35 to 100.00), and the accuracy 81%. This proof-of-principle study indicates that the early diagnosis of HGSOC is feasible through the analysis of genomic alterations in DNA from endocervical smears.

PURPOSE This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma.METHODSBetween May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL).RESULTSAfter a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) â ‰¥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs â ‰¥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80).CONCLUSIONThis trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.

Item does not contain fulltext, PURPOSE: This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma. METHODS: Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL). RESULTS: After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80). CONCLUSION: This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.

The objective of this work is to assess the 5-year outcomes of patients undergoing conization for high-grade cervical lesions that simultaneously present as risk factors in the persistence of HPV infection and the positivity of surgical resection margins. This is a retrospective study evaluating patients undergoing conization for high-grade cervical lesions. All patients included had both positive surgical margins and experienced HPV persistence at 6 months. Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). The charts of 2966 patients undergoing conization were reviewed. Among the whole population, 163 (5.5%) patients met the inclusion criteria, being at high risk due to the presence of positive surgical margins and experiencing HPV persistence. Of 163 patients included, 17 (10.4%) patients developed a CIN2+ recurrence during the 5-year follow-up. Via univariate analyses, diagnosis of CIN3 instead of CIN2 (HR: 4.88 (95%CI: 1.10, 12.41); p = 0.035) and positive endocervical instead of ectocervical margins (HR: 6.44 (95%CI: 2.80, 9.65); p < 0.001) were associated with increased risk of persistence/recurrence. Via multivariate analyses, only positive endocervical instead of ectocervical margins (HR: 4.56 (95%CI: 1.23, 7.95); p = 0.021) were associated with worse outcomes. In this high-risk group, positive endocervical margins is the main risk factor predicting 5-year recurrence.

INTRODUCTION: The use of routine antithrombotic prophylaxis is not recommended for advanced cancer patients receiving chemotherapy. The effect of bevacizumab-containing therapy on the risk of thromboembolic events remains controversial in ovarian cancer patients. We report on the incidence of thromboembolic events and the prevalence of antithrombotic therapy in patients enrolled in the single arm, phase IV, MITO-16A/MaNGO-OV2A trial. METHODS: In this trial, potential prognostic factors for patients with previously untreated ovarian cancer receiving a combination of platinum-based chemotherapy and bevacizumab were explored and the final analysis has already been reported. In this secondary analysis, the occurrence of thromboembolic events and the use of antithrombotic therapy were described according to the clinical characteristics of the patients. The prognostic role of thromboembolic events for progression-free and overall survival were also evaluated. RESULTS: From October 2012 to November 2014, 398 eligible patients were enrolled. 76 patients (19.1%) were receiving some type of anticoagulant or anti-aggregant treatment at baseline. Overall, 24 thromboembolic events were reported (cumulative incidence of 6.0%). The occurrence of thromboembolic events was not associated with baseline patient characteristics and was not modified by the use of antithrombotic prophylaxis (HR 0.60, 95% CI 0.18 to 2.0). Occurrence of thromboembolic events was not associated with progression-free survival (HR 1.34, 95% CI 0.83 to 2.15) or overall survival (HR 0.78, 95% CI 0.37 to 1.61). CONCLUSIONS: In our study, a 6.0% rate of thromboembolic events was reported during treatment with bevacizumab plus chemotherapy. Thromboembolic events were not associated with the clinical characteristics of the patients or with the use of antithrombotic prophylaxis, nor did they significantly affect the long-term prognosis. TRIAL REGISTRATION NUMBER: NCT01706120.

Objective: To assess predictors of recurrence following laparoscopic radical hysterectomy (LRH) for apparent early stage cervical cancer (CC). Methods: This is a retrospective multi-institutional study reviewing data of consecutive patients who underwent LRH for FIGO 2009 stage IA1 (with lymphovascular space invasion (LVSI)), IA2 and IB1(≤4 cm) CC, between January 2006 and December 2017. The following histotypes were included: squamous, adenosquamous, and adenocarcinoma. Multivariable models were used to estimate adjusted odds ratio (OR) and corresponding 95% CI. Factors influencing disease-free survival (DFS) and disease-specific survival (DSS) were also explored. Results: 428 patients were included in the analysis. With a median follow-up of 56 months (1–162) 54 patients recurred (12.6%). At multivariable analysis, tumor size (OR:1.04, 95%CI:1.01–1.09, p = .02), and presence of cervical residual tumor at final pathology (OR: 5.29, 95%CI:1.34–20.76, p = .02) were found as predictors of recurrence; conversely preoperative conization reduced the risk (OR:0.32, 95%CI:0.11–0.90, p = .03). These predictors remained significant also in the IB1 subgroup: tumor size: OR:1.05, 95%CI:1.01–1.09, p = .01; residual tumor at final pathology: OR: 6.26, 95%CI:1.58–24.83, p = .01; preoperative conization: OR:0.33, 95%CI:0.12–0.95, p = .04. Preoperative conization (HR: 0.29, 95%CI: 0.13–0.91; p = .03) and the presence of residual tumor on the cervix at the time of surgery (HR: 8.89; 95%CI: 1.39–17.23; p = .01) independently correlated with DFS. No independent factors were associated with DSS. Conclusions: In women with early stage CC the presence of high-volume disease at time of surgery represent an independent predictor of recurrence after LRH. Conversely, preoperative conization and the absence of residual disease at the time of surgery might play a protective role.

Objective: The European Society of Gynaecological Oncology (ESGO)-quality indicators (QIs) for advanced ovarian cancer (AOC) have been assessed only by few Italian centers, and data are not available on the proportion of centers reaching the score considered for a satisfactory surgical management. There is great consensus that the Enhanced Recovery After Surgery (ERAS) approach is beneficial, but there is paucity of data concerning its application in AOC. This survey was aimed at gathering detailed information on perioperative management of AOC patients within MITO-MaNGO Groups. Methods: A 66-item questionnaire, covering ESGO-QIs for AOC and ERAS items, was sent to MITO/MaNGO centers reporting to operate >20 AOC/year. Results: Thirty/34 questionnaires were analyzed. The median ESGO-QIs score was 31.5, with 50% of centers resulting with a score ≥32 which provides satisfactory surgical management. The rates of concordance with ERAS guidelines were 46.6%, 74.1%, and 60.7%, respectively, for pre-operative, intra-operative, and post-operative items. The proportion of overall agreement was 61.3%, and with strong recommendations was 63.1%. Pre-operative diet, fasting/bowel preparation, correction of anaemia, post-operative feeding and early mobilization were the most controversial. A significant positive correlation was found between ESGO-QIs score and adherence to ERAS recommendations. Conclusion: This survey reveals a satisfactory surgical management in only half of the centers, and an at least sufficient adherence to ERAS recommendations. Higher the ESGO-QIs score stronger the adherence to ERAS recommendations, underlining the correlations between case volume, appropriate peri-operative management and quality of surgery. The present study is a first step to build a structured platform for harmonization within MITO-MaNGO networks.

Surgery is the mainstay of treatment in the management of early-stage cervical cancer. Until the publication of the Laparoscopic Approach to Cervical Cancer (LACC) trial, minimally invasive radical hysterectomy was the recommended approach to treat patients with early-stage disease. The results of the LACC trial questioned the adoption of minimally invasive surgery in cervical cancer. In comparison with the open approach, minimally invasive surgery correlated with worse disease-free and cancer-specific survival. Similarly, other retrospective studies highlighted this correlation, thus corroborating the results of the LACC trials. In the present review, we evaluated current evidence and further prospective of the adoption of minimally invasive radical hysterectomy in cervical cancer. Moreover, we sought to assess some unsolved issues regarding the role of minimally invasive surgery in early-stage cervical cancer patients.

Objective: Only 10–15% of serous borderline ovarian tumors (BOTs) with extra-ovarian disease have invasive implants, and conservative treatments have been rarely reported. The MITO14 is a multi-institutional retrospective study conducted with the aim of systematically collecting data from consecutive BOT patients. The present analysis reports the oncological and reproductive outcomes of women with serous BOT and invasive implants registered into the MITO14 database and conservatively treated between August 2002 and May 2019. Methods: Thirteen patients (FIGO2014 stage II–III serous BOT with invasive implants) were recruited. Primary and secondary endpoints were, respectively, recurrence and death rates, and pregnancy and live birth rates. Only patients undergoing fertility-sparing surgery (FSS) were included, while patients were excluded in case of: age > 45 years; second tumor(s) requiring therapy interfering with the treatment of BOT. Results: Median follow-up time from primary cytoreduction was 146 months (range 27–213 months). Eleven patients (84.6%) experienced at least one recurrence (median time to first relapse 17 months, range 4–190 months), all of these undergoing secondary surgery (FSS in 7). Five patients attempted to conceive: 3 achieved at least one pregnancy and 2 gave birth at least to a healthy child. At the end of the observation period, all patients were alive with no evidence of disease. Conclusions: Fertility-sparing treatment should be considered in a context of serous BOT with invasive implants. Despite the high rate of recurrence, FSS provides good chances of reproductive success without a negative impact on overall survival.

Introduction The role of cytoreductive surgery in the poly-ADP ribose polymerase inhibitors era is not fully investigated. We evaluated the impact of surgery performed prior to platinum-based chemotherapy followed by olaparib maintenance in platinum-sensitive BRCA-mutated recurrent ovarian cancer. Methods This retrospective study included platinum-sensitive recurrent ovarian cancer BRCA-mutated patients from 13 Multicenter Italian Trials in Ovarian cancer and gynecological malignancies centers treated between September 2015 and May 2019. The primary outcomes were progression-free survival and overall survival. Data on post-progression treatment was also assessed. Results Among 209 patients, 72 patients (34.5%) underwent cytoreductive surgery followed by platinum-based chemotherapy and olaparib maintenance, while 137 patients (65.5%) underwent chemotherapy treatment alone. After a median follow-up of 37.3 months (95% CI: 33.4 to 40.8), median progression-free survival in the surgery group was not reached, compared with 11 months in patients receiving chemotherapy alone (P<0.001). Median overall survival was nearly double in patients undergoing surgery before chemotherapy (55 vs 28 months, P<0.001). Post-progression therapy was assessed in 127 patients: response rate to chemotherapy was 29.2%, 8.8%, and 9.0% in patients with platinum-free interval >12 months, between 6 and 12 months, and <6 months, respectively. Conclusion Cytoreductive surgery performed before platinum therapy and olaparib maintenance was associated with longer progression-free survival and overall survival in BRCA-mutated platinum-sensitive relapsed ovarian cancer patients. In accordance with our preliminary results, the response rate to chemotherapy given after progression during olaparib was associated with platinum-free interval.

A pregnancy related cancer is defined as a neoplasm diagnosed in a woman during gestation or within 12 months following childbirth or abortion. Breast, thyroidal, melanoma, cervical and hematological malignancies are those most commonly diagnosed during pregnancy, with a reported incidence considered lower than those estimated of 1 case on 1000 pregnancies. The clinical complexity is generated by the co-presence of mother and fetus, and the consequent conflict represented by the need to identify a therapeutic strategy that is effective for the maternal prognosis and, at the same time, safeguards the fetal well-being. Moreover, the counseling, diagnosis, staging and management of these cases are further complicated because most of the scientific literature consists in case reports or small retrospective studies and lacks in guidelines and prospective clinical trials. On that basis, the Study Group on Cancer in Pregnancy (members of S.I.G.O.-Italian Society of Gynecology and Obstetrics) presents the TIGRE Trial, an Italian multicenter observational study aimed at establishing a shared database for the collection of epidemiological and clinical data of the patients affected by pregnancy related cancer in Italy, with the final objective to improve the outcome of a mother and a child involved in a such pathology.

Ovarian cancer (OC) remains relatively rare, although it is among the top 4 causes of cancer death for women younger than 50. The aggressive nature of the disease and its often late diagnosis with peritoneal involvement have an impact on prognosis. The current scientific literature presents ambiguous or uncertain indications for management of peritoneal carcinosis (PC) from OC, both owing to the lack of sufficient scientific data and their heterogeneity or lack of consistency. Therefore, the Italian Society of Surgical Oncology (SICO), the Italian Society of Obstetrics and Gynaecology, the Italian Association of Hospital Obstetricians and Gynaecologists, and the Italian Association of Medical Oncology conducted a multidisciplinary consensus conference (CC) on management of advanced OC presenting with PC during the SICO annual meeting in Naples Italy, on September 10-11, 2015. An expert committee developed questions on diagnosis and staging work-up, indications, and procedural aspects for peritonectomy, systemic chemotherapy, and hyperthermic intraperitoneal chemotherapy for PC from OC. These questions were provided to 6 invited speakers who answered with an evidence-based report. Each report was submitted to a jury panel, representative of Italian experts in the fields of surgical oncology, gynecology, and medical oncology. The jury panel revised the reports before and after the open discussion during the CC. This article is the final document containing the clinical evidence reports and statements, revised and approved by all the authors before submission.

Background Few data are available on the outcome of surgery after a bevacizumab-containing regimen. The MITO 16A- MaNGO OV2A phase 4 trial evaluates the outcomes of first-line CPB in a clinical-practice-like setting. Here we present the results of the subgroup of patients undergoing IDS after neoadjuvant treatment or suboptimal primary surgery. Methods 400 chemonaïve epithelial ovarian cancer patients, age ≥ 18, ECOG PS 0–2 were eligible to receive C (AUC 5 d1, q21) plus P (175 mg/m2 d1, q21) and B (15 mg/kg d1 q21) for 6 cycles followed by B maintenance until cycle 22nd. Results 79 patients (20%) underwent IDS. Overall, 74 patients received at least one administration of B before IDS. Median age was 61.2, 70% of the patients had FIGO IIIC disease. The median number of cycles before IDS was 3 both for chemotherapy and bevacizumab respectively. A residual disease ≤ 1 cm was achieved in 64 patients (86.5%). Four percent of the patients experienced fever and 4% required blood transfusion after surgery. Surgical wound infection and/or dehiscence, pelvic abscess, intestinal sub-occlusion and fistula were experienced by one patient each. Conclusions In the MITO16A-MaNGO OV2A phase 4 trial, combined chemotherapy and bevacizumab did not hamper IDS and the rate of perioperative complications was similar to what expected without bevacizumab. These data support the hypothesis that adding bevacizumab to first line chemotherapy for ovarian cancer might not be denied to patients for whom IDS is planned.