Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994.

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.

Clinical characteristics and molecular aspects of low-grade serous ovarian and peritoneal cancer: a multicenter, observational, retrospective analysis of MITO Group (MITO 22).

BACKGROUND: Low-grade serous ovarian and peritoneal cancer (LGSC) is a rare disease and few data on the clinical and genomic landscape have been published. METHODS: A retrospective analysis of patients diagnosed with LGSC between 1996 and 2019 was conducted in MITO centers. Objective Response Rate (ORR) to treatments, progression-free survival (PFS) and overall survival (OS) were assessed. Additionally, the tumor molecular profile of 56 patients was evaluated using the Next Generation Sequencing (NGS) FoundationOne CDX (Foundation Medicine®). RESULTS: A total of 128 patients with complete clinical data and pathologically confirmed diagnosis of LGSC were identified. ORR to first and subsequent therapies were 23.7% and 33.7%, respectively. PFS was 43.9 months (95% CI:32.4-53.1) and OS was 105.4 months (95% CI: 82.7-not reached). The most common gene alterations were: KRAS (n = 12, 21%), CDKN2A/B (n = 11, 20%), NRAS (n = 8, 14%), FANCA (n = 8, 14%), NF1 (n = 7, 13%) and BRAF (n = 6, 11%). Unexpectedly, pathogenetic BRCA1 (n = 2, 4%), BRCA2 (n = 1, 2%) and PALB2 (n = 1, 2%) mutations were found. CONCLUSIONS: MITO 22 suggests that LGSC is an heterogenous disease for both its clinical behavior in response to standard therapies and its molecular alterations. Future prospective studies should test treatments according to biological and molecular tumor's characteristics. CLINICAL TRIAL REGISTRATION: This study is registered under NCT02408536 on ClinicalTrials.gov .

Evaluation of perioperative management of advanced ovarian (tubal/peritoneal) cancer patients: a survey from MITO-MaNGO Groups.

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.

Assessing the role of minimally invasive radical hysterectomy for early-stage cervical cancer.

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.

Olaparib beyond progression compared with platinum chemotherapy after secondary cytoreductive surgery in patients with recurrent ovarian cancer: phase III randomized, open-label MITO 35b study, a project of the MITO-MANGO groups.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors have transformed the management landscape for patients with ovarian cancer, demonstrating remarkable improvements in progression-free survival and overall survival. Unfortunately, most relapses are due to an acquired mechanism of resistance to these agents. We hypothesize that secondary cytoreductive surgery, removing resistant clones, might help to overcome the development of resistance to poly (ADP-ribose) polymerase inhibitors, prolonging their therapeutic effect. PRIMARY OBJECTIVE: To determine the efficacy of olaparib beyond progression compared with standard platinum-based chemotherapy in patients with recurrent ovarian cancer progressed during or after poly (ADP-ribose) polymerase inhibitor maintenance therapy after secondary cytoreductive surgery. STUDY HYPOTHESIS: Olaparib administered beyond progression is more effective in increasing progression-free survival and progression-free survival 2 compared with second-line platinum-based chemotherapy in patients after secondary cytoreductive surgery. TRIAL DESIGN: Phase III, randomized, open-label, multicenter trial. Eligible patients will be randomized in a 1:1 ratio to receive olaparib or platinum-based chemotherapy of the investigator's choice. MAJOR ELIGIBILITY CRITERIA: Eligible patients must have high-grade serous or endometrioid ovarian cancer progressed during or after first-line poly (ADP-ribose) polymerase inhibitor maintenance therapy and must have undergone secondary cytoreductive surgery. PRIMARY ENDPOINT: The dual primary endpoints will include progression-free survival and progression-free survival 2. Progression-free survival is defined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as the time between randomization and progression or death from any cause. Progression-free survival 2 is defined by the investigator using RECIST version 1.1 as the time frame from randomization to the second progression or death from any cause after subsequent treatment. SAMPLE SIZE: Approximately 200 patients will be enrolled in this study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Enrollment will be completed in 2024. Results will be presented in 2026. TRIAL REGISTRATION: EudraCT 2021-000245-41 NCT05255471.

Fertility-sparing treatment for serous borderline ovarian tumors with extra-ovarian invasive implants: Analysis from the MITO14 study database.

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.

Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer.

BACKGROUND: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear. METHODS: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival. RESULTS: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery. CONCLUSIONS: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.).

Thromboembolic events and antithrombotic prophylaxis in advanced ovarian cancer patients treated with bevacizumab: secondary analysis of the phase IV MITO-16A/MaNGO-OV2A trial.

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.

Bevacizumab, carboplatin, and paclitaxel in the first line treatment of advanced ovarian cancer patients: the phase IV MITO-16A/MaNGO-OV2A study.

OBJECTIVE: To explore the clinical and biological prognostic factors for advanced ovarian cancer patients receiving first-line treatment with carboplatin, paclitaxel, and bevacizumab. METHODS: A multicenter, phase IV, single arm trial was performed. Patients with advanced (FIGO (International Federation of Gynecology and Obstetrics) stage IIIB-IV) or recurrent, previously untreated, ovarian cancer received carboplatin (AUC (area under the curve) 5), paclitaxel (175 mg/m2) plus bevacizumab (15 mg/kg) on day 1 for six 3-weekly cycles followed by bevacizumab single agent (15 mg/kg) until progression or unacceptable toxicity up to a maximum of 22 total cycles. Here we report the final analysis on the role of clinical prognostic factors. The study had 80% power with a two-tailed 0.01 α error to detect a 0.60 hazard ratio with a factor expressed in at least 20% of the population. Both progression-free and overall survival were used as endpoints. RESULTS: From October 2012 to November 2014, 398 eligible patients were treated. After a median follow-up of 32.3 months (IQR 24.1-40.4), median progression-free survival was 20.8 months (95% CI 19.1 to 22.0) and median overall survival was 41.1 months (95% CI 39.1 to 43.5). Clinical factors significantly predicting progression-free and overall survival were performance status, stage, and residual disease after primary surgery. Neither baseline blood pressure/antihypertensive treatment nor the development of hypertension during bevacizumab were prognostic. There were two deaths possibly related to treatment, but no unexpected safety signal was reported. CONCLUSIONS: Efficacy and safety of bevacizumab in combination with carboplatin and paclitaxel and as maintenance were comparable to previous data. Hypertension, either at baseline or developed during treatment, was not prognostic. Performance status, stage, and residual disease after primary surgery remain the most important clinical prognostic factors. TRIAL REGISTRATION NUMBER: EudraCT 2012-003043-29; NCT01706120.

Cytoreductive surgery followed by chemotherapy and olaparib maintenance in BRCA 1/2 mutated recurrent ovarian cancer: a retrospective MITO group study.

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.

Fertility-sparing treatment in advanced-stage serous borderline ovarian tumors. An analysis from the MITO14 study database.

OBJECTIVES: To evaluate oncological and reproductive outcomes of women undergoing fertility-sparing surgery (FSS) for stage II-III serous borderline ovarian tumors (BOTs). METHODS: A multi-institutional retrospective study was conducted within the MITO Group. RESULTS: A total of 91 patients were recruited. The median follow-up time from primary cytoreduction was 127 months (IQR range 91-179). Forty-nine patients (53.8%) experienced at least one recurrence (median time to first relapse 22 months, IQR range 9.5-57). At univariable analysis, significant predictors of relapse were: size of largest extra-ovarian lesion, peritoneal cancer index, completeness of cytoreduction, type of implants. After multivariable analysis, the size of extra-ovarian lesions and the presence of invasive implants resulted as the only independent predictors of recurrence. Median disease-free survival (DFS) was 96 months (95% CI, 24.6-167.3), while median disease-specific survival (DSS) was not reached. Twenty-nine patients (31.8%) attempted to conceive: 20 (68.9%) achieved at least one pregnancy and 18 (62%) gave birth to a healthy child. At the end of the observation period, 88 patients (96.7%) showed no evidence of disease, 2 (2.2%) were alive with disease, and 1 patient (1.1%) died from BOT. CONCLUSIONS: Despite the recurrence high rate, FSS provides good chances of reproductive success with no impact on DSS. The presence of invasive peritoneal implants affects the DFS but not DSS nor reproductive outcome. The risk of recurrence would not seem to be related to the ovarian preservation per se, but to the natural history of the initial peritoneal spread.

Impact of COVID-19 in gynecologic oncology: a Nationwide Italian Survey of the SIGO and MITO groups.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) has caused rapid and drastic changes in cancer management. The Italian Society of Gynecology and Obstetrics (SIGO), and the Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) promoted a national survey aiming to evaluate the impact of COVID-19 on clinical activity of gynecologist oncologists and to assess the implementation of containment measures against COVID-19 diffusion. METHODS: The survey consisted of a self-administered, anonymous, online questionnaire. The survey was sent via email to all the members of the SIGO, and MITO groups on April 7, 2020, and was closed on April 20, 2020. RESULTS: Overall, 604 participants completed the questionnaire with a response-rate of 70%. The results of this survey suggest that gynecologic oncology units had set a proactive approach to COVID-19 outbreak. Triage methods were adopted in order to minimize in-hospital diffusion of COVID-19. Only 38% of gynecologic surgeons were concerned about COVID-19 outbreak. Although 73% of the participants stated that COVID-19 has not significantly modified their everyday practice, 21% declared a decrease of the use of laparoscopy in favor of open surgery (19%). However, less than 50% of surgeons adopted specific protection against COVID-19. Additionally, responders suggested to delay cancer treatment (10%-15%), and to perform less radical surgical procedures (20%-25%) during COVID-19 pandemic. CONCLUSIONS: National guidelines should be implemented to further promote the safety of patients and health care providers. International cooperation is of paramount importance, as heavily affected nations can serve as an example to find out ways to safely preserve clinical activity during the COVID-19 outbreak.

Cytoreductive Surgery for Heavily Pre-Treated, Platinum-Resistant Epithelial Ovarian Carcinoma: A Two-Center Retrospective Experience.

Few retrospective studies have shown a benefit in selected patients affected by heavily pre-treated, platinum-resistant ovarian carcinomas (PROCs) who have undergone cytoreduction at relapse. However, the role of tertiary and quaternary cytoreductive surgery is not fully defined. Our aim was to evaluate survival and surgical morbidity and mortality after maximal cytoreduction in this setting. We evaluated all consecutive patients undergoing cytoreduction for platinum-resistance over an 8-year period (2010-2018) in two different centers. Fifty patients (median age 52.5 years, range 34-75) were included; the median number of previous chemotherapy lines was three (range 1-7) and the median number of previous surgeries was one (range 1-4). Completeness of cytoreduction (CC = 0) was achieved in 22 patients (44%). Rates of major operative morbidity and 30-day mortality were 38% and 8%, respectively. Median follow-up was 35 months. The absence of tumor residual (CC = 0) was associated with a significantly better overall survival (OS) compared to the CC > 0 subgroup (median OS 32.9 months (95% CI 21.6-44.2) vs. 4.8 months (95% CI n.a.-9.8), hazard ratio (HR) 4.21 (95% CI 2.07-8.60), p < 0.001). Optimal cytoreduction is feasible and associated with promising OS in selected, heavily pre-treated PROCs. Further prospective studies are required to better define the role of surgery in platinum-resistant disease.

Immunotherapy in cervix cancer.

The treatment approach to cervix cancer has remained unchanged for several decades and new therapeutic strategies are now required to improve outcomes, as the prognosis is still poor. In the last years, a better understanding of HPV tumor-host immune system interactions and the development of new therapeutics targeting immune checkpoints generated interest in the use of immunotherapy in cervix cancer. Preliminary phase I-II trials demonstrated the efficacy, the duration of responses and the manageable safety of this approach. Currently, many phase II and III studies are ongoing in both locally advanced and metastatic cervical cancer, assessing immunotherapy as a single agent or in combination with chemotherapy and radiotherapy. We reviewed the published data and the therapeutic implications of the most promising novel immunotherapeutic agents under investigation in cervix cancer.

Survival implication of lymphadenectomy in patients surgically treated for apparent early-stage uterine serous carcinoma.

OBJECTIVE: Uterine serous carcinoma (USC) is a rare highly aggressive disease. In the present study, we aimed to investigate the survival implication of the systematic lymphadenectomy in patients who underwent surgery for apparent early-stage USC. METHODS: Consecutive patients with apparent early-stage USC surgically treated at six Italian referral cancer centers were analyzed. A comparison was made between patients who underwent retroperitoneal staging including at least pelvic lymphadenectomy "LND" vs. those who underwent hysterectomy alone "NO-LND". Baseline, surgical and oncological outcomes were analyzed. Kaplan- Meier curves were calculated for disease-free survival (DFS) and disease-specific survival (DSS). Associations were evaluated with Cox proportional hazard regression and summarized using hazard ratio (HR). RESULTS: One hundred forty patients were analyzed, 106 LND and 34 NO-LND. NO-LND group (compared to LND group) included older patients (median age, 73 vs.67 years) and with higher comorbidities (median Charlson Comorbidity Index, 6 vs. 5) (p<0.001). No differences in terms of recurrence rate (LND vs. NO-LND, 33.1% vs. 41.4%; p=0.240) were observed. At Cox regression analysis lymphadenectomy did not significantly influence DFS (HR=0.59; 95% confidence interval [CI]=0.32-1.08; p=0.09), and DSS (HR=0.14; 95% CI=0.02-1.21; multivariable analysis p=0.07). Positive node was independently associated with worse DFS (HR=6.22; 95% CI=3.08-12.60; p<0.001) and DSS (HR=5.51; 95% CI=2.31-13.10; p<0.001), while adjuvant chemotherapy was associated with improved DFS (HR=0.38; 95% CI=0.17-0.86; p=0.02) and age was independently associated with worse DSS (HR=1.07; 95% CI=1.02-1.13; p<0.001). CONCLUSIONS: Although lymphadenectomy did not show survival benefits in patients who underwent surgery for apparent early-stage USC, the presence of lymph node metastasis was the main adverse prognostic factors, supporting the prognostic role of the retroperitoneal staging also in this histological subtype.

Fertility-sparing treatment for intramucous, moderately differentiated, endometrioid endometrial cancer: a Gynecologic Cancer Inter-Group (GCIG) study.

OBJECTIVE: 'The Endometrial Cancer Conservative Treatment (E.C.Co.). A multicentre archive' is a worldwide project endorsed by the Gynecologic Cancer Inter-Group, aimed at registering conservatively treated endometrial cancer (EC) patients. This paper reports the oncological and reproductive outcomes of intramucous, G2, endometrioid EC patients from this archive. METHODS: Twenty-three patients (Stage IA, G2, endometrioid EC) were enrolled between January 2004 and March 2019. Primary and secondary endpoints were, respectively, complete regression (CR) and recurrence rates, and pregnancy and live birth rates. RESULTS: A median follow-up of 35 months (9-148) was achieved. Hysteroscopic resection (HR) plus progestin was adopted in 74% (17/23) of cases. Seventeen patients showed CR (median time to CR, 6 months; 3-13). Among the 6 non-responders, one showed persistence and 5 progressed, all submitted to definitive surgery, with an unfavorauble outcome in one. The recurrence rate was 41.1%. Ten (58.8%) complete responders attempted to conceive, of whom 3 achieved at least one pregnancy with a live-birth. Two out of the 11 candidate patients underwent definitive surgery, while the remaining 9 have so far refused. To date, 22 patients show no evidence of disease, and one is still alive with disease. CONCLUSIONS: Fertility-sparing treatment seems to be feasible even in G2 EC, although caution should be kept considering the potential pathological undergrading or non-endometrioid histology misdiagnosis. The low rate of attempt to conceive and of compliance to definitive surgery underline the need for a 'global' counselling extended to the follow-up period.

Evaluation of surgical resection in advanced ovarian, fallopian tube, and primary peritoneal cancer: laparoscopic assessment. A European Network of Gynaecological Oncology Trial (ENGOT) group survey.

OBJECTIVE: Laparoscopy is one of the diagnostic tools available for the complex clinical decision-making process in advanced ovarian, fallopian tube, and peritoneal carcinoma. This article presents the results of a survey conducted within the European Network of Gynaecological Oncology Trial (ENGOT) group aimed at reviewing the current patterns of practice at gynecologic oncology centers with regard to the evaluation of resection in advanced ovarian, fallopian tube, and peritoneal carcinoma. METHODS: A 24-item questionnaire was sent to the chair of the 20 cooperative groups that are currently part of the ENGOT group, and forwarded to the members within each group. RESULTS: A total of 142 questionnaires were returned. Only 39 respondents (27.5%) reported using some form of clinical (not operative) score for the evaluation of resection. The frequency of use of diagnostic laparoscopy to assess disease status and feasibility of resection was as follows: never, 21 centers (15%); only in select cases, 83 centers (58.5%); and routinely, 36 centers (25.4%). When laparoscopy was performed, 64% of users declared they made the decision to proceed with maximal effort cytoreductive surgery based on their personal/staff opinion, and 36% based on a laparoscopic score. To the question of whether laparoscopy should be considered the gold standard in the evaluation of resection, 71 respondents (50%) answered no, 66 respondents (46.5%) answered yes, whereas 5 respondents (3.5%) did not provide an answer. CONCLUSIONS: This study found that laparoscopy was routinely performed to assess feasibility of cytoreduction in only 25.4% of centers in Europe. However, it was commonly used to select patients and in a minority of centers it was never used . When laparoscopy was adopted, the treatment strategy was based on laparoscopic scores only in a minority of centers.

Surgical Management of Early Cervical Cancer: When Is Laparoscopic Appropriate?

PURPOSE OF REVIEW: This paper reviews the recent literature data on minimally invasive surgical approach to early cervical cancer compared to abdominal approach, with the aim of evaluate the oncological outcomes and the appropriateness of current indications. RECENT FINDINGS: A recent multicenter randomized controlled trial and a concurrent large epidemiological study, contrary to the previous retrospective data, showed that minimally invasive surgery is associated with significantly poorer survival than the open approach. Open surgery is to be considered the standard of care for early cervical cancer as implemented in the current guidelines, and the patients must be carefully counseled if minimally invasive surgery is offered. Minimally invasive surgery can be considered safe only for sentinel lymph node mapping in a fertility-sparing setting and could be considered after preoperative conization and for small tumors, adopting preventive surgical maneuvers and in reference centers. However, prospective evidences about the suggested indications are not yet available.