Discordance between GCIG CA-125 progression and RECIST progression in the CALYPSO trial of patients with platinum-sensitive recurrent ovarian cancer.

BACKGROUND: CA-125 alone is widely used to diagnose progressive disease (PD) in platinum-sensitive recurrent ovarian cancer (PSROC) on chemotherapy. However, there are increasing concerns regarding its accuracy. We assessed concordance between progression defined by CA-125 and RECIST using data from the CALYPSO trial. METHODS: We computed concordance rates for PD by CA-125 and RECIST to determine the positive (PPV) and negative predictive values (NPV). RESULTS: Of 769 (79%) evaluable participants, 387 had CA-125 PD, where only 276 had concordant RECIST PD (PPV 71%, 95% CI 67-76%). For 382 without CA-125 PD, 255 had RECIST PD but 127 did not (NPV 33%, 95% CI 29-38). There were significant differences in NPV according to baseline CA-125 (≤100 vs >100: 42% vs 25%, P < 0.001); non-measurable vs measurable disease (51% vs 26%, P < 0.001); and platinum-free-interval (>12 vs 6-12 months: 41% vs 14%, P < 0.001). We observed falling CA-125 levels in 78% of patients with RECIST PD and CA-125 non-PD. CONCLUSION: Approximately 2 in 3 women with PSROC have RECIST PD but not CA-125 PD by GCIG criteria. Monitoring CA-125 levels alone is not reliable for detecting PD. Further research is required to investigate the survival impact of local therapy in radiological detected early asymptomatic PD.

Impact of different follow-up regimens on health-related quality of life and costs in endometrial cancer patients: Results from the TOTEM randomized trial.

PURPOSE: To investigate whether intensive follow-up (INT) after surgery for endometrial cancer impact health-related quality of life (HRQoL) and healthcare costs compared to minimalist follow-up (MIN), in the absence of evidence supporting any benefit on 5-year overall survival. METHODS: In the TOTEM trial, HRQoL was assessed using the SF-12 and the Psychological General Well-Being (PGWB) questionnaires at baseline, after 6 and 12 months and then annually up to 5 years of follow-up. Costs were analyzed after 4 years of follow-up from a National Health Service perspective, stratified by risk level. The probability of missing data was analyzed for both endpoints. RESULTS: 1847 patients were included in the analyses. The probability of missing data was not influenced by the study arms (MIN vs INT OR: 0.97 95%CI: 0.87-1.08). Longitudinal changes in HRQoL scores did not differ between the two follow-up regimens (MIN vs INT SF-12 PCS: -0.573, CI95%: -1.31; 0.16; SF-12 MCS: -0.243, CI95%: -1.08; 0.59; PGWB: -0.057, CI95%: -0,88; 0,77). The mean cost difference between the intensive and minimalist arm was €531 for low-risk patients and €683 for high-risk patients. CONCLUSION: In the follow-up of endometrial cancer after surgery, a minimalist treatment regimen did not affect quality of life and was cost-saving in both low-risk and high-risk recurrence patients. As previous results showed no survival benefit, a minimalist approach is justified. The relevant proportion of missing data on secondary outcomes of interest could be a critical point that deserves special attention.

A prospective, multicenter, randomized, double-blind placebo-controlled trial on purified and specific Cytoplasmic pollen extract for hot flashes in breast cancer survivors.

OBJECTIVE: evaluate the efficacy and tolerability of PureCyTonin against hot flashes (HF) in breast cancer survivors (BCS). METHODS: a prospective, multicenter, randomized, double-blind placebo-controlled trial was conducted in Italy. INTERVENTIONS: administration of PureCyTonin or placebo, for 3 months. Effectiveness was investigated through the compilation of a daily diary for HF and of validated questionnaires (Menopause Rating Scale (MRS), Pittsburgh Sleep Quality Index (PSQI), Visual Analogical Scales (VAS) for HF, sweating, irritability, fatigue, sleep, quality of life), carried out before starting the treatment (T0), after 1 month (T1) and after 3 months (T2). Any side effects and HF diary were recorded at each visit. RESULTS: 19 women were randomized to receive PureCyTonin and 20 to placebo. At T2 compared to T0, in the PureCyTonin group, we found a reduction in the number of HF (p = 0.02) measured by daily diary. An improvement in the subjective perception of women regarding HF intensity (p = 0.04), sweat nuisance (p = 0.02), irritability (p = 0.03) and fatigue (p = 0.04) was observed through VAS scale measurement at T2 compared to T0.The total MRS score was significantly better in the PureCyTonin group at T1 (p = 0.03) compared to T0. CONCLUSIONS: PureCyTonin significantly reduces HF number after 3 months of therapy in BCS and it is well-tolerated.

Ultrasonographic diagnosis of adnexal masses: interobserver agreement in the interpretation of videos, using IOTA terminology.

OBJECTIVES: Aim of this study is to estimate interobserver agreement in classifying adnexal tumors using IOTA terms, simple rules and subjective assessment. In addition, we related observers' accuracy with their experience in gynecological ultrasonography and the year of IOTA certification. METHODS: Eleven observers with three different levels of experience evaluated videoclips of 70 adnexal masses, defining tumor type according to IOTA terms and definitions, classifying the mass using IOTA Simple rules and Subjective assessment as well as providing Color Score evaluation. Sensitivity, specificity and area under the ROC curve were calculated and the year of IOTA certification was related with operators' accuracy through Pearson correlation coefficient. Interobserver agreement was estimated calculating percentage of agreement, Fleiss kappa and Cohen's kappa. RESULTS: We found a positive correlation between the year of IOTA certification and operators' accuracy (Pearson coefficient 0.694), especially among the observers with the least experience, the residents (p = 0.003). For tumor type classification, identification of papillary projections and classification of tumors using subjective assessment, agreement among all observers was moderate (Fleiss kappa 0.455, 0.552, and 0.476, respectively) and increased with the years of experience. Agreement in the application of Simple Rules was moderate in all examiners with IOTA certification, with Fleiss kappa in the range of (0.403, 0.498). For Color Score assignment interobserver agreement among all observers was fair (Cohen's kappa 0.380). CONCLUSIONS: Even among expert examiners, the results of adnexal lesion assessment can be inconsistent. Experience impacts on accuracy and agreement in subjective assessment, while the application of Simple Rules can mitigate the role of experience in interobserver agreement. The knowledge of IOTA models among residents seams to improve their diagnostic accuracy, showing the benefits of IOTA terminology for in training sonographers.

PARP Inhibitors in Brain Metastases from Epithelial Ovarian Cancer through a Multimodal Patient Journey: Case Reports and Literature Review.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy worldwide. Brain metastasis (BM) is quite an uncommon presentation. However, the likelihood of central nervous system (CNS) metastasization should be considered in the context of disseminated disease. The therapeutic management of BMs is an unmet clinical need, to date. We identified, across different cancer centers, six cases of both BRCA wild-type and BRCA-mutated EOCs spreading to the CNS. They presented either with a single brain lesion or with multiple lesions and most of them had intracranial-only disease. All cases received Poly-ADP ribose polymerase inhibitor (PARPi) maintenance, as per clinical practice, for a long time within a multimodal treatment approach. We also provide an insight into the available body of work regarding the management of this intriguing disease setting, with a glimpse of future therapeutic challenges. Despite the lack of unanimous guidelines, multimodal care pathways should be encouraged for the optimal disease control of this unfortunate patient subset. Albeit not being directly investigated in BM patients, PARPi maintenance is deemed to have a valuable role in this setting. Prospective research, aimed to implement worthwhile strategies in the multimodal patient journey of BMs from EOC, is eagerly awaited.

Development and clinical application of a tool to identify frailty in elderly patients with gynecological cancers.

OBJECTIVE: Frailty is more reliable than chronological age in predicting the effectiveness and tolerability of treatments in cancer patients. An increasing number of screening tools have been proposed, however none have received unanimous consent or been specifically designed for women with gynecological malignancies.This study's aim was to develop a clinical application of a screening tool to identify frail patients >70 years old diagnosed with either ovarian or endometrial cancers. METHODS: A 20 item questionnaire was developed and administered to the cohort before surgery or neoadjuvant chemotherapy. A cut-off for frailty definition was determined by analyzing the correlation of questionnaire scores with the completion of treatments. The association between frailty and treatment related complications was assessed using a Chi-squared test for categorical variables and a t-test for continuous variables. RESULTS: Our study included 100 patients, 50% diagnosed with endometrial cancer and 50% with ovarian cancer. A questionnaire score of 4 was the best cut-off for frailty definition (sensitivity 77%, specificity 100%). Surgical grade III and grade IV complications were observed only in frail patients (p=0.01) and hospitalization was significantly longer in frail women affected by ovarian cancer (p=0.01). Frail patients were more exposed to chemotherapy administration delay (p=0.0005), treatment discontinuation (p=0.001) and hematological toxicities, especially anemia ≥grade 2 (p=0.009) and thrombocytopenia any grade (p=0.0001). CONCLUSION: With a cut-off score of 4, our tool can identify frail patients with significantly higher incidence of grade III-IV postoperative complications, length of stay, medical treatment discontinuation rates and hematological toxicities.

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE).

OBJECTIVE: Primary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%-1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube carcinoma. METHODS: We retrospectively identified patients with FIGO stage I-IV, all histology types and grading primary fallopian tube carcinoma treated in three major oncological centers between January 2000 and March 2020. Exclusion criteria were bulky tubo-ovarian carcinomas, isolated serous tubal intraepithelial carcinoma or neoadjuvant chemotherapy. RESULTS: A total of 61 patients were included. The vast majority of primary fallopian tube carcinomas were serous (96.7%) and poorly differentiated (96.7%) and arose from the fimbriated end of the tube (88.5%). Larger tumor size correlated with higher probability of correct preoperative differential diagnosis of primary fallopian tube carcinoma (p=0.003). Up to 82.4% of patients with small tumors (≤15 mm) presented with high FIGO stage (≥IIA). The most common site of metastasis was pelvic peritoneum (18.8%) and among 59% of patients who underwent lymphadenectomy smaller tumors had higher rate of nodal metastasis (42.9%≤10 mm vs 27.3%>50 mm). After 46.0 months of mean follow-up there were 27 recurrences (48.2%). The most common site of relapse was diffuse peritoneal spread (18.5%). The 5-year disease-free survival was 45.2% and 5-year overall survival was 75.5%. Of note, 42.9% of patients with stage IVB survived >36 months. CONCLUSION: Primary fallopian tube carcinoma is a biologically distinct tumor from primary epithelial ovarian carcinoma and it is mostly located in the fimbriated end of the tube. In addition, it is characterized by a high rate of retroperitoneal dissemination even at apparently an early stage and its size does not correlate with FIGO stage at presentation.

EANM guideline on the role of 2-[18F]FDG PET/CT in diagnosis, staging, prognostic value, therapy assessment and restaging of ovarian cancer, endorsed by the American College of Nuclear Medicine (ACNM), the Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the International Atomic Energy Agency (IAEA).

In most patients with ovarian carcinoma, the diagnosis is reached when the disease is long past the initial stages, presenting already an advanced stage, and they usually have a very bad prognosis. Cytoreductive or debulking surgical procedures, platinum-based chemotherapy and targeted agents are key therapeutic elements. However, around 7 out of 10 patients present recurrent disease within 36 months from the initial diagnosis. The metastatic spread in ovarian cancer follows three pathways: contiguous dissemination across the peritoneum, dissemination through the lymphatic drainage and, although less importantly in this case, through the bloodstream. Radiological imaging, including ultrasound, CT and MRI, are the main imaging techniques in which management decisions are supported, CT being considered the best available technique for presurgical evaluation and staging purposes. Regarding 2-[18F]FDG PET/CT, the evidence available in the literature demonstrates efficacy in primary detection, disease staging and establishing the prognosis and especially for relapse detection. There is limited evidence when considering the evaluation of therapeutic response. This guideline summarizes the level of evidence and grade of recommendation for the clinical indications of 2-[18F]FDG PET/CT in each disease stage of ovarian carcinoma.

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.

Report from the 21st meeting of the European Society of Gynaecological Oncology (ESGO 2019).

This is a report from the 21st Meeting of the European Society of Gynaecological Oncology (ESGO 2019) held in Athens, Greece, November 2-5, 2019. The conference offered state of the art educational sessions, and oral and poster abstract presentations. The general sessions throughout the meeting focused not only on prevention, screening, diagnosis, treatment, and translational research but also on emerging trends. Current innovations in gynecological cancers were also discussed. The new rare tumor guidelines project, a joint initiative with the ESGO-Gynecologic Cancer InterGroup, was officially presented for the first time. Moreover, other developments achieved with other societies, such as the European Society for Medical Oncology for ovarian cancer, the European Federation for Colposcopy for cervical cancer prevention and screening, and the European Society for Pediatric Oncology for gynecologic cancers in adolescents, were presented. Here we highlight the key results of the latest gynecological cancer trials that were presented for the first time at ESGO 2019 and added great value to this prestigious scientific congress.

Multicenter, randomised, open-label, non-comparative phase 2 trial on the efficacy and safety of the combination of bevacizumab and trabectedin with or without carboplatin in women with partially platinum-sensitive recurrent ovarian cancer.

BACKGROUND: Trabectedin, in addition to its antiproliferative effect, can modify the tumour microenvironment and this could be synergistic with bevacizumab. The efficacy and safety of trabectedin and bevacizumab ± carboplatin have never been investigated. METHODS: In this phase 2 study, women progressing between 6 and 12 months since their last platinum-based therapy were randomised to Arm BT: bevacizumab, trabectedin every 21 days, or Arm BT+C: bevacizumab, trabectedin and carboplatin every 28 days, from cycles 1 to 6, then trabectedin and bevacizumab as in Arm BT. Primary endpoints were progression-free survival rate (PFS-6) and severe toxicity rate (ST-6) at 6 months, assuming a PFS-6 ≤35% for BT and ≤40% for BT+C as not of therapeutic interest and, for both arms, a ST-6 ≥ 30% as unacceptable. RESULTS: BT+C (21 patients) did not meet the safety criteria for the second stage (ST-6 45%; 95%CI: 23%-69%) but PFS-6 was 85% (95%CI: 62%-97%). BT (50 patients) had 75% PFS-6 (95%CI: 60%-87%) and 16% ST-6 (95%CI 7%-30%). CONCLUSIONS: BT compared favourably with other platinum- and non-platinum-based regimens. The combination with carboplatin needs to be assessed further in a re-modulated safer schedule to confirm its apparent strong activity. CLINICAL TRIAL REGISTRATION: NCT01735071 (Clinicaltrials.gov).

Predictors of extensive lymphatic dissemination and recurrences in node-positive endometrial cancer.

OBJECTIVE: To identify predictors of extensive lymphatic dissemination and distant recurrences in node-positive endometrial cancer (EC). METHODS: Clinicopathologic data were collected of patients who had fully staged EC with at least 1 positive lymph node. Permanent sections of metastatic lymph nodes were reviewed; metastases were characterized according to size (≤2 mm and >2 mm) and location in the lymph node (intra- vs extracapsular). Risk of occurrence of multiple pelvic and para-aortic lymph node dissemination was calculated by combining risk factors identified at multivariate analysis. RESULTS: Of 96 patients, 85 had positive pelvic nodes, of whom 71 (83.5%) had high-volume metastases. In the presence of both macrometastasis in the pelvic basin (odds ratio [OR], 13.42; [95% CI, 2.44-73.83]) and uterine serosal involvement of the tumor at final pathologic evaluation (OR, 11.84 [95% CI, 1.22-115.11]), multiple pelvic node dissemination occurred in 91.7% of cases (vs 7.7% in the absence of both). Concomitant presence of pelvic macrometastasis, lymphovascular space invasion (LVSI), and extracapsular invasion led to 85.7% occurrence of para-aortic involvement (vs 11.1% if no factors present). LVSI was independently associated with nonvaginal recurrences (hazard ratio, 2.62 [95% CI, 1.33-5.16]). CONCLUSIONS: Presence of high-volume metastases in the pelvic lymph nodes is associated with concomitant presence of multiple positive pelvic nodes, as well as para-aortic node involvement. LVSI is associated with both para-aortic node involvement and occurrence of nonvaginal relapses. In this era of sentinel lymph node mapping, these factors may help predict the extent of lymphatic dissemination in EC.

Oral metronomic cyclophosphamide in advanced ovarian cancer: long-lasting clinical response in an elderly frailty patient.

Elderly patients with ovarian cancer are an increasing population and many of them are frailty with an increased risk of postoperative complications, chemotherapy intolerance and mortality. Metronomic chemotherapy is the chronic administration of low, equally spaced, doses of antineoplastic drugs with therapeutic efficacy and low toxicity. Oral metronomic cyclophosphamide has gained increasing interest in recent years in the treatment of patients with recurrent ovarian cancer. We report the case of a 87-year-old and -frailty woman with advanced ovarian cancer, not eligible for surgery or standard first-line intravenous chemotherapy. The patient has received oral metronomic cyclophosphamide with a long-lasting clinical response and improved performance status. Oral metronomic cyclophosphamide is a promising treatment for elderly and frailty advanced ovarian cancer patients and should be further investigated.

Development of a preoperative computed tomography score for the management of advanced epithelial ovarian cancer.

OBJECTIVE: The main objective is to develop a model based on computed tomographic features to predict surgical outcome and establish cut-offs to rationalize clinical management in advanced epithelial ovarian carcinoma. The secondary purpose is to identify parameters that should be reported by radiologists to allow a correct pre-operative evaluation. METHODS: This study evaluated the association between 17 radiologic parameters and surgical outcome through the review of 61 computed tomographic scans. Each parameter received a score according to the strength of statistical association and points were added to obtain a predictive index value. The absence of residual tumor was considered an optimal result. Receiver operating characteristic curves were applied to assess the ability to predict surgical outcome. The score was applied to the study population to verify if the therapeutic approach had been congruent with the predicted results and to define adequate cut-offs. RESULTS: Analysis with a receiver operating characteristic curve demonstrated a statistical association with surgical outcome (area under curve=0.949). The clinical approach agreed with the predicted outcome. Patients with lower scores received primary debulking surgery (mean predictive index value 2.4) whereas those with higher scores (mean 14.1) were given neoadjuvant chemotherapy. Further surgical investigation (laparoscopy) was performed in patients with higher predictive index value variability (0-17.5). Different cut-offs were analysed to define the model applicability. The results show that surgery is appropriate for patients with a predictive index value <6 (failure rate 11.5%) while a predictive index value >8 should address to neoadjuvant chemotherapy (0% of inappropriately unexplored patients). In addition, patients with a predictive index value between 6 and 8 could benefit from diagnostic exploration with a good success rate (71.4%). CONCLUSIONS: The model correctly discerns patients who can benefit from surgery (predictive index value <6) from those who should undergo neoadjuvant chemotherapy (>8) and establishes a range (6-8) where surgical investigations may be helpful. This score is a flexible tool where cut-offs can be changed according to the desire to be surgically more aggressive or more conservative.

Clinical pathways of recovery after surgery for advanced ovarian/tubal/peritoneal cancer: an NSGO-MaNGO international survey in collaboration with AGO-a focus on surgical aspects.

OBJECTIVES: This survey assessed the implementation of enhanced recovery after surgery (ERAS) for patients undergoing surgery for advanced ovarian cancer in three European cooperative study groups in Scandinavia, Italy, and Austria. The aim was to evaluate the landscape for future trials on ERAS pathways in ovarian cancer, because high-level evidence for such interventions is lacking. METHODS: In July 2017, a web-based questionnaire (SurveyMonkey Inc, Palo Alto, CA, USA) was sent to centers conducting surgery for advanced ovarian cancer within the Nordic Society of Gynecologic Oncology (NSGO), Mario Negri Gynecologic Oncology Group (MaNGO) and other Italian institutions, and the Association for Gynecologic Oncology Austria (AGO Austria) (n = 100). The survey covered all aspects of an ERAS pathway including surgery, nursing, and anesthesia. We herein report on the survey findings relating to surgery, including nursing care issues; however, anesthesiologic issues will be discussed in a separate report. RESULTS: The overall response rate was 62%. Only a third of the centers in Italy and Austria follow a written ERAS protocol compared with 60% of the Scandinavian centers. Only a minority of centers have completely abandoned bowel preparation, with the highest proportion in Scandinavia (36%). Two hours of fasting for fluids before surgery is routinely practiced in Scandinavia and Austria (67-57%, respectively), but not in Italy (5%). Carbohydrate loading is routinely administered only in Scandinavia (67%). Peritoneal drainage is used by 22% routinely and by 61% in cases of bowel resection/lymphadenectomy/peritonectomy. Early feeding with a light diet on day 0 or 1 is the standard of care in Scandinavia and Austria, but not in Italy. CONCLUSIONS: The degree of implementation of ERAS protocols varies across and within cooperative groups. The centralization of ovarian cancer care seems to facilitate standardization of peri-operative protocols. Currently, the high heterogeneity in patterns of care may challenge an international approach to a clinical trial.

The effect of a uterine manipulator on the recurrence and mortality of endometrial cancer: a multi-centric study by the Italian Society of Gynecological Endoscopy.

BACKGROUND: Although widely adopted, the use of a uterine manipulator during laparoscopic treatment of endometrial cancer represents a debated issue, and some authors hypothesize that it potentially may cause an increased risk of relapse, particularly at specific sites. OBJECTIVE: Our aim was to evaluate the risk and site of disease recurrence, overall survival, and disease-specific survival in women who had laparoscopic surgery with and without the use of a uterine manipulator. STUDY DESIGN: Data were reviewed from consecutive patients who had laparoscopic surgery for endometrial cancer staging in 7 Italian centers. Subjects were stratified according to whether a uterine manipulator was used during surgery; if so, the type of manipulator was identified. Multivariable analysis to correct for possible confounders and propensity score that matched the minimize selection bias were utilized. The primary outcome was the risk of disease recurrence. Secondary outcomes were disease-specific and overall survival and the site of recurrence, according to the use or no use of the uterine manipulator and to the different types of manipulators used. RESULTS: We included 951 patients: 579 patients in the manipulator group and 372 patients in the no manipulator group. After a median follow-up period of 46 months (range,12-163 months), the rate of recurrence was 13.5% and 11.6% in the manipulator and no manipulator groups, respectively (P=.37). Positive lymph nodes and myometrial invasion of >50% were associated independently with the risk of recurrence after adjustment for possible confounders. The use of a uterine manipulator did not affect the risk of recurrence, both at univariate (odds ratio, 1.18; 95% confidence interval, 0.80-1.77) and multivariable analysis (odds ratio, 1.00; 95% confidence interval, 0.60-1.70). Disease-free, disease-specific, and overall survivals were similar between groups. Propensity-matched analysis confirmed these findings. The site of recurrence was comparable between groups. In addition, the type of uterine manipulator and the presence or not of a balloon at the tip of the device were not associated significantly with the risk of recurrence. CONCLUSION: The use of a uterine manipulator during laparoscopic surgery does not affect the risk of recurrence and has no impact on disease-specific or overall survival and on the site of recurrence in women affected by endometrial cancer.

Ovarian Cancer in Elderly Patients: Patterns of Care and Treatment Outcomes According to Age and Modified Frailty Index.

OBJECTIVE: The present study assessed the predictive value of age and Modified Frailty Index (mFI) on the management of primary epithelial ovarian cancer (EOC) patients aged 70 years or older (elderly). METHODS: A retrospective multicenter study selected elderly EOC patients treated between 2006 and 2014. Treatments were analyzed according to the following age group categories: (1) 70 to 75 years versus (2) older than 75 years, and mFI of less than 4 (low frailty) versus greater than or equal to 4 (high frailty). RESULTS: Seventy-eight patients were identified (40 in age group 1 and 38 in age group 2). The mFI was greater than or equal to 4 in 23 women. Median age of low frailty and high frailty was not significantly different (75.6 vs 75.3). Comorbidities were equally distributed according to age, whereas diabetes, hypertension, obesity, and chronic renal failure were more frequent in the high-frailty group. Performance status was different only according to mFI. Twenty percent of age group 1 versus 55.3% of age group 2 underwent none or only explorative surgical approach (P = 0.003), whereas surgical approaches were similar in the 2 frailty groups. The rate of postoperative complications was higher in high-frailty patients compared with low-frailty patients (23.5% vs 4.3%; P = 0.03). Chemotherapy was administered to all the patients, a monotherapy regimen to 50% of them. No differences in toxicity were registered, except more hospital recovery in the high-frailty cohort. Median survival time was in favor of younger patients (98 versus 30 months) and less-frailty patients (56 vs 27 months). CONCLUSIONS: Elderly EOC patients can receive an adequate treatment, but patients who are older than 75 years can be undertreated, if not adequately selected. The pretreatment assessment of frailty through mFI could be suggested in the surgical and medical management.

Laparoscopic vs. open treatment of endometrial cancer in the elderly and very elderly: An age-stratified multicenter study on 1606 women.

Objective To investigate in depth the effect of increasing age on the peri-operative outcomes of laparoscopic treatment for endometrial cancer, compared to open surgery, with stratification of patients according to the different definitions of elderly age used in the literature. METHODS: Data of consecutive patients who underwent surgery for endometrial cancer staging at six centers were reviewed and analyzed according to surgical approach (laparoscopic or open), different definitions of elderly and very elderly age (≥65years, ≥75years, ≥80years), and class of age (<65; ≥65-<75; ≥75-80; ≥80years). Multivariable analysis to correct for possible confounders and propensity-score matching to minimize selection bias were used. RESULTS: A total of 1606 patients were included: 938 and 668 patients received laparoscopic and open surgery, respectively. With increasing age, fewer patients received laparoscopy (P<0.001 with ANOVA). The percentage of patients who received lymphadenectomy declined significantly in both groups for age ≥80years. Blood transfusions, incidence and severity of post-operative complications, and hospital stay were significantly lower among patients who had laparoscopy both in younger (<65years) and elderly (whether defined as ≥65 or ≥75years) patients, with no effect of age on any of the characteristics analyzed ( ANOVA: P>0.05). The same tendency was observed among very-elderly patients (≥80years). Multivariable and propensity score-matched analysis confirmed these findings. CONCLUSIONS: Laparoscopy for staging endometrial cancer retains its advantages over open surgery even in elderly and very-elderly patients. Our data strongly suggest that minimally-invasive surgery is advantageous even among subjects ≥80years.