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Purpose: The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results., Methods: We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen., Results: A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99-7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66-3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68-1.19); p = 0.479)., Conclusion: Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used., (© 2023. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: To establish a prognostic model for endometrial cancer (EC) that individualizes a risk and management plan per patient and disease characteristics., Methods: A multicenter retrospective study conducted in nine European gynecologic cancer centers. Women with confirmed EC between January 2008 to December 2015 were included. Demographics, disease characteristics, management, and follow-up information were collected. Cancer-specific survival (CSS) and disease-free survival (DFS) at 3 and 5 years comprise the primary outcomes of the study. Machine learning algorithms were applied to patient and disease characteristics. Model I: pretreatment model. Calculated probability was added to management variables (model II: treatment model), and the second calculated probability was added to perioperative and postoperative variables (model III)., Results: Of 1150 women, 1144 were eligible for 3-year survival analysis and 860 for 5-year survival analysis. Model I, II, and III accuracies of prediction of 5-year CSS were 84.88%/85.47% (in train and test sets), 85.47%/84.88%, and 87.35%/86.05%, respectively. Model I predicted 3-year CSS at an accuracy of 91.34%/87.02%. Accuracies of models I, II, and III in predicting 5-year DFS were 74.63%/76.72%, 77.03%/76.72%, and 80.61%/77.78%, respectively., Conclusion: The Endometrial Cancer Individualized Scoring System (ECISS) is a novel machine learning tool assessing patient-specific survival probability with high accuracy., (© 2022 International Federation of Gynecology and Obstetrics.)

Objective: To compare outcomes between minimally invasive surgery and open surgery in patients with high-risk endometrial cancer., Data Sources: A cohort study of all patients who underwent surgery for high-risk endometrial cancer between 1999 and 2016 at Mayo Clinic (Rochester, Minnesota) and a literature search of MEDLINE, EMBASE, ClinicalTrials.gov, Cochrane Central Register of Controlled Trials, and Scopus of all published studies until December 2020., Methods of Study Selection: The systematic review identified 2,332 patients (14 studies, all retrospective except a subanalysis of a randomized comparison) and the cohort study identified 542 additional patients. Articles were included if reporting original data on overall survival and disease-free survival among patients with high-risk endometrial cancer, defined as International Federation of Gynecology and Obstetrics grade 3 endometrioid, serous, clear cell, mixed histology, or uterine carcinosarcoma. Studies that did not report at least one of the main outcomes, those in which one surgical technique (robotic or laparoscopic surgery) was missing in the comparison analysis with open surgery, and case reports were excluded. Additional data were extracted from a retrospective cohort of patients from Mayo. A random-effect model was used for meta-analysis., Tabulation, Integration, and Results: This systematic review and meta-analysis was registered in PROSPERO. Literature search and data extraction were performed independently by two reviewers, as well as quality assessment using GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology, and the Newcastle-Ottawa Scale. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed. Meta-analysis showed that disease-free survival and overall survival in patients with high-risk endometrial cancer who underwent minimally invasive surgery were not statistically different from those of patients who underwent open abdominal surgery (relative risk [RR] 0.93, 95% CI 0.82-1.05, I2 20%, P=.23; and RR 0.92, 95% CI 0.77-1.11, I2 31%, P=.12, respectively). Subgroup analysis by stage (early vs advanced) did not identify a difference between surgical approaches., Conclusion: Minimally invasive surgery and open surgery had similar disease-free survival and overall survival in patients with high-risk endometrial cancer., Systematic Review Registration: PROSPERO, CRD42021275535., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2022 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The main goal of this study is to assess the diagnostic agreement between preoperative biopsy and definitive histology of the surgical specimen to determine which sampling method is most suitable for diagnosis of early-stage endometrial cancer., Methods: We performed a retrospective multicentric study to assess the correlation between three endometrial sampling methods (hysteroscopy, pipelle and D&C) in patients who had undergone preoperative endometrial biopsy and received primary surgical treatment for endometrial cancer. The primary objective was the agreement rate between hysteroscopy (HSC), endometrial biopsy (pipelle) and dilatation and curettage (D&C)., Results: A total of 1833 women who underwent preoperative sampling at 15 centers were included: 1042 biopsies were performed by HSC, 703 by pipelle and 88 by D&C. All three methods presented a moderate diagnostic concordance (κ = 0.40-0.61) with the definitive specimen's histology: HSC (κ = 0.47), pipelle sampling (κ = 0.48) and D&C (κ = 0.48). Likewise, a subgroup analysis was performed by histological subtype comparing HSC and endometrial biopsy, showing that neither is superior as a diagnostic method., Conclusions: According to this study, the use of pipelle sampling could become an adequate diagnostic method in endometrial cancer due to its similar agreement to HSC, ease of use and affordability., (© 2022. The Author(s), under exclusive licence to Federación de Sociedades Españolas de Oncología (FESEO).)

Objective: The primary objective was to evaluate the response rate of conservative treatment for endometrial cancer, and the secondary objective was to assess oncological, fertility and obstetric outcomes in patients who underwent fertility preservation treatment., Material and Methods: This multicentre, observational, retrospective study evaluated endometrial cancer patients who underwent fertility-sparing treatment in Spanish centres between January 2010 and January 2020. Seventy-three patients with stage IA endometrioid adenocarcinoma of the uterus were included in the study., Results: The levonorgestrel intrauterine device (LNG-IUD) was the most common fertility-sparing treatment (53.4%), followed by megestrol acetate (20.5%) and medroxyprogesterone acetate (16.4%). During the 24-month follow-up period, the rate of complete response to fertility-sparing management was 74% (n = 54), and 8.2% (n = 6) of patients presented a partial response. Additionally, 13 (17.8%) patients presented with persistent disease and six (8.2%) relapsed after response. The LNG-IUD was associated with a higher complete response rate than the other methods (87.2 vs. 58.8%; p = 0.01). Surgical treatment (at least hysterectomy) was performed in 44 (60.3%) patients as the end of fertility-sparing treatment. Four (5.5%) patients presented relapse after surgery, associated with final FIGO stage III (p = 0.036), myometrial invasion > 50% (p = 0.018) and final tumour grade 2-3 (p = 0.018). The mean follow-up period was 57.8 (range 6-159) months. The 5-year relapse-free survival and overall survival rates were 92.6% [95% CI (81.3, 97.2)] and 93.5% [95% CI (80.7, 97.9)], respectively. During follow-up, three patients (4.1%) died of the disease after completion of surgical treatment. Up to 50.7% of patients included in the study attempted to get pregnant. Of these, the rate of pregnancy was 81.1% (n = 30/37), and reproductive techniques were used for this purpose in 78.4% of cases., Conclusions: Fertility-sparing management presented a high response rate in patients with endometrial cancer. LNG-IUD was associated with a better response rate compared to the other treatment options. Moreover, in patients using this management method, pregnancy could be achieved using reproductive techniques., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The aim of the study was to determine if the endometrial tumor volume (TV) measured by magnetic resonance imaging (MRI-TV) is associated with survival in endometrial cancer and lymph nodes metastases (LN+)., Patients and Methods: We evaluated the MRI imaging and records of 341 women with endometrial cancer and preoperative MRI from 2008 to 2018. The MRI-TV was calculated using the ellipsoid formula measuring three perpendicular tumor diameters. Tumor myometrial invasion was also analyzed., Results: Higher MRI-TV was associated with age ≥ 65y, non-endometrioid tumors, grade-3, deep-myometrial invasion, LN+ and advanced FIGO stage. There were 37 patients with LN+ (8.8%). Non-endometrioid tumors, deep-myometrial invasion, grade-3 and MRI-TV ≥ 10 cm 3 were the factors associated with LN+. Using a receiver operating characteristic [ROC] curve, the MRI-TV cut-off for survival was 10 cm 3 (area under curve [AUC] = 0.70; 95% CI: 0.61-0.73). 5 years disease-free (DFS) and overall survival (OS) was significantly lower in MRI-TV ≥ 10 cm 3 (69.3% vs . 84.5%, and 75.4% vs . 96.1%, respectively). MRI-TV was considered an independent factor of DFS (HR: 2.20, 95% CI: 1.09-4.45, p = 0.029) and OS (HR: 3.88, 95% CI: 1.34-11.24, p = 0.012) in multivariate analysis., Conclusions: MRI-TV was associated with LN+, and MRI-TV ≥ 10 cm 3 was an independent prognostic factor of lower DFS and OS. The MRI-TV can be auxiliary information to plan the surgery strategy and predict the adjuvant treatment in women with endometrial cancer., (© 2021 Pluvio J. Coronado, Javier de Santiago-López, Javier de Santiago-García, Ramiro Méndez, Maria Fasero, Miguel A. Herraiz, published by Sciendo.)

Background: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience., Objective: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer., Study Design: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence., Results: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27-4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I-II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57-0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07-2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63)., Conclusion: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I-II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Olaparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1, 2, and 3 with potential activity in endometrial cancer (EC)., Methods: In this window-of-opportunity trial, women with operable type 1 EC received olaparib oral tablets (300mg) twice daily for 28days before surgery. The primary objective was to evaluate the effects of olaparib on EC in tissue samples taken at baseline and at treatment completion. Signal of activity was defined as significant changes in the expression of the cell cycle-related proteins cyclin D1, Ki67, and cleaved caspase-3., Results: A total of 31 patients were included in the biomarker analysis. The median time of olaparib exposure was 24 days (1-39). Significant inhibition was found for cyclin D1 (p < 0.01), but not for Ki67 and active caspase 3 immunostaining. PARP-1 levels positively correlated with cyclin D1 levels (rho = 0.661, p = 0.0001). Both PARP-1 and cyclin D1 levels were significantly lower (p = 0.022 and p = 0.004, respectively) in patients with ARID1A[-] tumors than ARID1A[+] tumors. A significant relationship between plasma olaparib concentrations and decreased GLUT1 activity was observed (r = -0.5885; p < 0.05). Drug-related toxicity consisted mostly of gastrointestinal and grade 1 or 2 adverse events., Conclusions: Olaparib reduced expression of cyclin D1, which positively correlated with PARP-1 levels. This effect was more evident in ARID1A-deficient tumors. Olaparib further induced inhibition of GLUT1 plasma activity. Our findings could have noteworthy implications in predicting which patients with EC would benefit from olaparib-based strategies., Competing Interests: Declaration of Competing Interest Ignacio Romero: consulting or advisory role for AstraZeneca Spain, GSK Tesaro Spain, Roche Spain, Clovis Spain. Juan-Antonio Schoenenberger: funds from MedSIR for the submitted work. Eva Maria Guerra: consulting fees and advisory board fees from Roche, Clovis Oncology, GSK Tesaro, PharmaMar, AstraZeneca, Merck Sharp & Dohme; travel support from Roche, GSK Tesaro and Baxter. Alfonso Cortés: consulting fees or speaker bureau from AstraZeneca, Roche-Genentech, Pfizer, Lilly, Ferrer. Juan Fernando Cueva: consulting fees from AstraZeneca. Lourdes Gómez and Andrea Malfettone: full-time employees of MedSIR. Miguel Sampayo: consulting fees from Syntax for Science, Nestle Health Science, Laboratorios Leti, Roche, Ability Pharma and Allergan; part-time employee of MedSIR. Antonio Llombart-Cussac: leadership of Eisai, Celgene, Lilly, Pfizer, Roche, Novartis, MSD; stock or other ownership of MedSIR, Initia-Research; consulting or advisory role for Lilly, Roche, Pfizer, Novartis, Pierre-Fabre, GenomicHealth, GSK; speakers' bureau from Lilly, AstraZeneca, MSD; research funding from Roche, Foundation Medicine, Pierre-Fabre, Agendia; travel, accommodations, expenses from Roche, Lilly, Novartis, Pfizer, AstraZeneca. Andrés Poveda: consulting or advisor role for AstraZeneca, PharmaMar, Clovis Oncology, Roche, GSK Tesaro. M. Jesús Rubio, Manuel Medina, Xavier Matias-Guiu, Maria Santacana, Lucas Minig, and Pluvio Coronado: no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: To compare perioperative outcomes and complications in robotically assisted laparoscopy (RAL) and standard laparoscopy (SLP) approaches in the treatment of endometrial cancer by body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters)., Methods: A comparative study was carried out of women treated for endometrial cancer at the Hospital Clinico San Carlos from January 2012 to December 2016: 133 patients were operated by RAL and 101 by SLP. Demographic characteristics of the patients, perioperative outcomes and complications were compared in both approaches., Results: Hospital stay was significantly lower in patients with BMI ≤30 operated with RAL (2 days RAL vs 4 days SLP; P=0.002). Estimated blood loss was significantly lower in the group with BMI<25 (60 mL RAL vs 100 mL SLP; P=0.004) and in the group with BMI ≥30 (87.5 mL RAL vs 180 SLP; P=0.003) operated with RAL. RAL significantly reduced the conversion rate in patients with BMI ≥30 (2 [3.4%] patients RAL vs 6 [27.3%] patients SLP; P=0.004)., Conclusions: RAL has demonstrated advantages in treating obese women with endometrial cancer by reducing blood loss and conversion to laparotomy., (© 2020 International Federation of Gynecology and Obstetrics.)

Objective: To assess the impact of lymph node dissection (LND) on morbidity, survival, and cost for intermediate-risk endometrial cancers (IREC)., Methods: A multicenter retrospective cohort of 720 women with IREC (endometrioid histology with myometrial invasion <50% and grade 3; or myometrial invasion ≥50% and grades 1-2; or cervical involvement and grades 1-2) was carried out. All patients underwent hysterectomy and bilateral salpingo-oophorectomy. A matched pair analysis identified 178 pairs (178 with LND and 178 without it) equal in age, body mass index, co-morbidities, American Society of Anesthesiologist score, myometrial invasion, and surgical approach. Demographic data, pathology results, perioperative morbidity, and survival were abstracted from medical records. Disease-free survival (DFS) and overall survival (OS) was analyzed using Kaplan-Meier curves and multivariate Cox regression analysis. Cost analysis was carried out between both groups., Results: Both study groups were homogeneous in demographic data and pathologic results. The mean follow-up in patients free of disease was 61.7 months (range, 12.0-275.5). DFS (hazard ratio [HR]=1.34; 95% confidence interval [CI]=0.79-2.28) and OS (HR=0.72; 95% CI=0.42-1.23) were similar in both groups, independently of nodes count. In LND group, positive nodes were found in 10 cases (5.6%). Operating time and late postoperative complications were higher in LND group (p<0.05). Infection rate was significantly higher in no-LND group (p=0.035). There were no statistical differences between both groups regarding operative morbidity and hospital stay. The global cost was similar for both groups., Conclusion: Systematic LND in IREC has no benefit on survival, although it does not show an increase in perioperative morbidity or global cost., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology)

Objective: The aim of this study is to assess the impact of lymphadenectomy (LND) on morbidity, survival, and cost for high-risk histologic types of endometrial cancer (EC)., Materials and Methods: We analyzed a multicenter retrospective cohort of 389 women with high-risk histotypes of EC (poor differenced tumors [G3], clear cell, serous papillary, and mixed mesodermal tumors) preoperatively confined to the corpus and diagnosed between 2000 and 2013. All patients underwent hysterectomy and bilateral salpingo-oophorectomy. A matched-pair analysis identified 97 pairs (97 with LDN and 97 without) equal in age, body mass index, comorbidities, International Federation of Gynecology and Obstetrics stage, and adjuvant treatment. Demographic data, pathologic examination results, perioperative morbidity, and survival were abstracted from medical records. Cost was provided by the cost unit of the local hospital. Disease-free and overall survival were analyzed using the Kaplan-Meier curves and Cox multivariable regression analysis., Results: Both study groups were homogeneous in demographic data and pathologic examination results. At a median follow-up of 24.5 months (range, 5.4-146.3), disease-free survival (hazard ratio, 1.09; 95% confidence interval, 0.70-1.90) and overall survival (hazard ratio, 0.86; 95% confidence interval, 0.56-1.33) were similar in both groups regardless of nodal count. Positive nodes were found in 23.7%. Predictor factors of nodal involvement were advanced age (P = 0.024), deep myometrial invasion (P < 0.001), and high CA 125 levels (P = 0.003). In the LDN group, operating time, late postoperative complications, and surgical cost were higher (P < 0.05). There were no statistical differences between both groups relative to surgical morbidity. Early postoperative complications and hospital stay were lower in the LDN group. The global cost was similar for both groups (6027&OV0556; for the LND group and 5772&OV0556; for the no-LND group)., Conclusions: Lymphadenectomy in high-risk histotypes of EC does not increase perioperative morbidity or global cost and has not benefit on survival.

Objective: To analyze the perioperative outcomes and cost of three surgical approaches in the treatment of endometrial cancer: robotic, laparoscopy and laparotomy., Study Design: We studied 347 patients with endometrial cancer treated in a single institution: 71 patients were operated by robotics, 84 by conventional laparoscopy and 192 by laparotomy. All patients underwent total hysterectomy, bilateral salpingoophorectomy and pelvic and para-aortic lymphadenectomy depending on the pathological features., Results: Operative time was longer in the laparoscopy group as compared to robotics and laparotomy (218.2 min, 189.2 min, and 157.4 min respectively, p=0.000). The estimated blood loss was lower in the robotic group relative to the other groups (99.4 ml in robotic, 190.0 ml in laparoscopy and 231.5 ml in laparotomy, p=0.000). Similar findings were observed for the pre- and post-operative mean hemoglobin levels (-1.3g/dl, -2.3g/dl and -2.5 g/dl respectively, p=0.000), and transfusion rate (4.2%, 7.1% and 14.1% respectively, p=0.036). The length of hospital stay was higher in the laparotomy group compared to robotics and laparoscopy (8.1, 3.5 and 4.6 days respectively; p=0.000). The conversion rate to laparotomy was lower for robotics (2.4% for robotics and 8.1% for laparoscopy, p=0.181). Overall complications were similar for robotics and laparoscopy (21.1%, 28.5%) (p=0.079). Robotic complications were significantly lower as compared to laparotomy (21.2 vs 34.9% (p=0.036). No differences were found relative to disease-free or overall survival among the three groups. The global costs were similar for the three approaches (p=0.566)., Conclusion: Robotics is a safe alternative to laparoscopy and laparotomy for endometrial cancer patients, offering improved perioperative outcomes and similar cost as compared to the other two surgical approaches., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)