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Objective: This study aimed to compare survival and complications between minimally invasive surgery and open surgery and evaluate related risk factors in patients with non-endometrioid endometrial cancer., Methods: Clinicopathologic characteristics; survival outcomes; complications; and prognostic factors associated with progression-free survival and overall survival were compared among patients with non-endometrioid endometrial cancer who underwent primary staging surgery using laparoscopic, robotic, or open abdominal surgery (2004-2017)., Results: In total, 91 patients were included: 41 and 50 underwent minimally invasive surgery and open surgery, respectively. The minimally invasive surgery and open surgery groups showed similar progression-free survival (5-year progression-free survival rate, 58.7 % vs. 58.5 %; P = .925) and overall survival (5-year overall survival rate, 73.6 % vs. 80.3 %; P = .834). Intraoperative (7.2 % vs. 6.0 %; P = .111) and postoperative surgical complications (14.6 % vs. 26.0 %; P = .165) were similar between the groups. However, blood loss was lower (mean, 305.1 vs. 561.2 ml, P < .001) and hospital stay was shorter (mean, 8.2 vs. 15.4 days, P < .001) in the minimally invasive surgery group. Using multivariate analysis, lymphovascular space invasion was identified as poor prognostic factor for progression-free survival (adjusted hazard ratio [HR], 3.054; 95 % confidence interval [CI], 1.521-6.132; P = .002) and overall survival (adjusted HR, 3.918; 95 % CI, 1.455-10.551; P = .007), whereas age ≥ 60 years was poor prognostic factor for only overall survival (adjusted HR, 5.0953; 95 % CI, 1.660-15.378; P = .004)., Conclusions: Surgical outcomes did not differ between the minimally invasive and open surgery group in patients with non-endometrioid endometrial cancer. Lymphovascular space invasion was a significant survival factor in this context., (Copyright © 2024 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

The Gynecologic Cancer InterGroup (GCIG) Endometrial Cancer Consensus Conference on Clinical Research (ECCC) was held in Incheon, South Korea, Nov 2-3, 2023. The aims were to develop consensus statements for future trials in endometrial cancer to achieve harmonisation on design elements, select important questions, and identify unmet needs. All 33 GCIG member groups participated in the development, refinement, and finalisation of 18 statements within four topic groups, addressing adjuvant treatment in high-risk disease; treatment for metastatic and recurrent disease; trial designs for rare endometrial cancer subgroups and special circumstances; and specific methodology and adaptation for trials in low-resource settings. In addition, eight areas of unmet need were identified. This was the first GCIG Consensus Conference to include patient advocates and an expert on inclusion, diversity, equity, and access to take part in all aspects of the process and output. Four early-career investigators were also selected for participation, ensuring that they represented different GCIG member groups and regions. Unanimous consensus was obtained for 16 of the 18 statements, with 97% concordance for the remaining two. Using the described methodology from previous Ovarian Cancer Consensus Conferences, this conference did not require even one minority statement. The high acceptance rate following active involvement in the preparation, discussion, and refinement of the statements by all representatives confirmed the consensus progress within a global academic setting, and the expectation that the ECCC will lead to greater harmonisation, actualisation, inclusion, and resolution of unmet needs in clinical research for individuals living with and beyond endometrial cancer worldwide., Competing Interests: Declaration of interests All authors report that the KGOG paid for their 2-night hotel stay and basic meals during the 2 days of the ECCC on Clinical Research meeting. CLC reports a research grant paid to her institution from Varian; payment to her institution for participation on a data safety monitoring board from Merck; and unpaid roles as chair of GCIG Endometrial Committee and member of Guidelines Committees for Endometrial cancer of the European Society of Gynaecologic Oncology (ESGO) and the European Society of Radiotherapy and Oncology. GE reports personal consulting fees from MSD, personal fees from Eisai, and support for attending a meeting or travel from MSD. LE reports personal consulting fees AstraZeneca, GSK, and MSD; personal fees from AstraZeneca and GSK, and support for attending a meeting or travel from AstraZeneca and GSK. RAN reports research grants paid to his institution from Elekta, Varian, and Accuray; and payment to his institution for presentations from Elekta and MSD. DL reports research grants both personal and paid to her institution from AstraZeneca, Clovis Oncology, Genmab, GSK, Immunogen, MSD, Novartis, Pharmamar, and Seagen; personal grants from Corcept, Oncoinvest, and Sutro; and grants to her institution from Incyte and Roche; consulting fees from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro; payment for presentations from Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro; support for attending a meeting or travel from AstraZeneca, Clovis Oncology, MSD and GSK; and payments for participation on a data safety monitoring board from AstraZeneca, Clovis Oncology, Corcept, Genmab, GSK, Immunogen, MSD, Novartis, Oncoinvest, Pharmamar, Seagen, and Sutro. AO reports research grants paid to his institution from AstraZeneca; consulting fees from Bristol Myers Squibb, uncompensated participation on data and safety monitoring boards of studies funded by AstraZeneca and GlaxoSmithKline; and unpaid roles as principal investigator on investigator-initiated trials and on steering committees of trials funded by AstraZeneca and GlaxoSmithKline. BP reports research grants from Tesaro/GSK, Merck, AstraZeneca, Karyopharm Therapeutics, Sutro, Incyte, Clovis Oncology, Roche/Genentech, Mersana, Celsion/Immunon, Imab, Takeda, Toray, VBL Therapeutics, InxMed, Agenus, Seagen, NRG Oncology, Duality Bio, Xencor, Onconova, Celgene, Sutro Biopharma, Novocure, Immunogen, Eisai, Acrivon, and Alkermes; consulting fees from Tesaro/GSK, AstraZeneca, Merck, Immunogen, Gynecologic Oncology Group (GOG) Foundation, SeaGen, Lily, Eisai, Signatera, Celsion, Butro Biopharma, Imvax, Incyte, InxMed, Onconova Therapeutics, R Pharm, Regeneron, and Duality Bio; payment for presentations from Bioascend, PERS, Vanium, Curio, OncLive, Yale University and PeerView; support for attending a meeting or travel from GOG Partners, payment for participation on a data safety monitoring board or advisory board from Sutro, AstraZeneca, GOG Foundation, Celsion/Immunon, Toray, InxMed, Imvax, Imab, Tesaro/GSK, Merck, Mersana, Nuvation, and BioNtech; and unpaid leadership roles in boards, societies and committees: Society of Gynecologic Oncology (SGO) Clinical Practice Committee Chair, SGO Board of Directors, SGO COVID-19 Taskforce co-chair, GOG Partners, and New York Obstetrical Society Second VP. BH reports textbook royalties from Elsevier; consulting fees from Tempus; honoraria for lectures from Leica and Projects in Knowledge; and unpaid leadership roles on the International Society of Gynecological Pathologists Board of Directors (as member at large) and on the Endometrial Cancer MSI Committee of the College of American Pathologists. IR-C reports research grants from AstraZeneca, Clovis, GSK, Mersana, BMS, and MSD; payment for presentations from AstraZeneca, Clovis, GSK, Mersana, BMS, MSD, Roche, Pharmamar, Seagen, Eisai, and Novartis; support for attending a meeting or travel from Roche, GSK, AstraZeneca, Pharmamar, and MSD; and payment for participation on a data safety monitoring board or advisory board from Clovis, Deciphera, Adaptimmue, Sutro, and Immunogen. DG reports support for attending meetings or travel from IGCS Board of Directors; payment for participation on a data and safety monitoring board from Merck, and a leadership role in NRG Oncology. AM reports payment for participation as independent statistician on data safety monitoring boards from ONY Biotech, Regeneron, and Genentech/Roche. NC reports payments or honoraria for presentations from GSK, Seagen, Akesobio, AstraZeneca, eTheRNA immunotherapies NV, Kartos, MSD, Mersana, ImmunoGen, Eisai, Seattle Genetics, TouchIME, and Medscape Oncology; support for attending a meeting or travel from Roche, Genmab, and Amgen; payment for participation on a data safety monitoring board or advisory board from GSK, Mersana, Seagen, ImmunoGen, Akesobio, Eisai, AstraZeneca, Mersana, Seattle Genetics, eTheRNA immunotherapies NV, and Kartos; and leadership roles as President of ESGO and Chair of European Network for Gynaecological Oncological Trial groups Early Drug Development Network. MAP reports grants paid to his institution from GSK; payment for participation on a data and safety monitoring board from GSK, AstraZeneca, Eisai, Merck, Immunogen, Clovis Oncology, Jazz Pharma, and SeaGen; and payment to his institution for a leadership role on a board or committee from NRG Oncology. MAB reports payment to his institution for participation on a data and safety monitoring board from Immunogen; and employment as physician at The Permanente Medical Group. J-WK, EA, SIK, J-YP, LM, PBO, AB, DM, VG, TB, CG, TM, HW, XM-G, WS, and GS declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objectives: Fertility-sparing treatment (FST) might be considered an option for reproductive patients with low-risk endometrial cancer (EC). On the other hand, the matching rates between preoperative assessment and postoperative pathology in low-risk EC patients are not high enough. We aimed to predict the postoperative pathology depending on preoperative myometrial invasion (MI) and grade in low-risk EC patients to help extend the current criteria for FST., Methods/materials: This ancillary study (KGOG 2015S) of Korean Gynecologic Oncology Group 2015, a prospective, multicenter study included patients with no MI or MI <1/2 on preoperative MRI and endometrioid adenocarcinoma and grade 1 or 2 on endometrial biopsy. Among the eligible patients, Groups 1-4 were defined with no MI and grade 1, no MI and grade 2, MI <1/2 and grade 1, and MI <1/2 and grade 2, respectively. New prediction models using machine learning were developed., Results: Among 251 eligible patients, Groups 1-4 included 106, 41, 74, and 30 patients, respectively. The new prediction models showed superior prediction values to those from conventional analysis. In the new prediction models, the best NPV, sensitivity, and AUC of preoperative each group to predict postoperative each group were as follows: 87.2%, 71.6%, and 0.732 (Group 1); 97.6%, 78.6%, and 0.656 (Group 2); 71.3%, 78.6% and 0.588 (Group 3); 91.8%, 64.9%, and 0.676% (Group 4)., Conclusions: In low-risk EC patients, the prediction of postoperative pathology was ineffective, but the new prediction models provided a better prediction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: In the global phase 3 Study 309/KEYNOTE-775 (NCT03517449) at the first interim analysis, lenvatinib+pembrolizumab significantly improved progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) versus treatment of physician's choice chemotherapy (TPC) in patients with previously treated advanced/recurrent endometrial cancer (EC). This exploratory analysis evaluated outcomes in patients enrolled in East Asia at the time of prespecified final analysis., Methods: Women ≥18 years with histologically confirmed advanced, recurrent, or metastatic EC with progressive disease after 1 platinum-based chemotherapy (2 if 1 given in neoadjuvant/adjuvant setting) were enrolled. Patients were randomized 1:1 to lenvatinib 20 mg orally once daily plus pembrolizumab 200 mg intravenously every 3 weeks (≤35 cycles) or TPC (doxorubicin or paclitaxel). Primary endpoints were PFS per RECIST v1.1 by blinded independent central review and OS. No alpha was assigned for this subgroup analysis., Results: Among 155 East Asian patients (lenvatinib+pembrolizumab, n=77; TPC, n=78), median follow-up time (data cutoff: March 1, 2022) was 34.3 (range, 25.1-43.0) months. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS (lenvatinib+pembrolizumab vs. TPC) were 0.74 (0.49-1.10) and 0.64 (0.44-0.94) in the mismatch repair proficient (pMMR) and all-comer populations, respectively. HRs (95% CI) for OS were 0.68 (0.45-1.02) and 0.61 (0.41-0.90), respectively. ORRs were 36% with lenvatinib+pembrolizumab and 22% with TPC (pMMR) and 39% and 21%, respectively (all-comers). Treatment-related adverse events occurred in 97% and 96% (grade 3-5, 74% and 72%), respectively., Conclusion: Lenvatinib+pembrolizumab provided clinically meaningful benefit with manageable safety compared with TPC, supporting its use in East Asian patients with previously treated advanced/recurrent EC., Trial Registration: ClinicalTrials.gov Identifier: NCT03517449., Competing Interests: Kan Yonemori has received lecture fees from Eisai, Pfizer, Eli Lilly, Takeda, Chugai, Fuji Film Pharma, PDR pharma, Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA (MSD), Boeringer Ingelheim, Ono, Daiichi-Sankyo, Bayer, Jansen, Sanofi, and AstraZeneca; is a member of the advisory board for Eisai, AstraZeneca, Sanofi, Genmab, Gilead, OncXerna, Takeda, Novartis, and MSD; research funding from MSD, Daiichi-Sankyo, Merck Biopharma, AstraZeneca, Taiho, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boehringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe; and is principle investigator for MSD, Daiichi-Sankyo, AstraZeneca, Taiho, Merk Biopharma, Pfizer, Novartis, Takeda, Chugai, Ono, Sanofi, Seattle Genetics, Eisai, Eli Lilly, Genmab, Boeringer Ingelheim, Kyowa Hakko Kirin, Nihon Kayaku, and Haihe., (© 2024. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Objective: To investigate the prognostic significance of L1 cell-adhesion molecule (L1CAM), β-catenin, and programmed death-ligand 1 (PD-L1) in endometrial cancer (EC) patients, with a focus on p53 wild-type subgroup, for additional risk stratification., Methods: This retrospective cohort study included EC patients classified according to Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE) who underwent primary surgical treatment at the single center between January 2014 and December 2018. Immunohistochemical staining was performed for four mismatch repair (MMR) proteins, p53, L1CAM, β-catenin, and PD-L1. DNA polymerase epsilon (POLE) mutation was detected by hot spot sequencing via droplet digital polymerase chain reaction. Survival outcome of each subgroup of L1CAM, β-catenin, and PD-L1 was measured according to their expression., Results: A total of 162 EC patients were included. Endometrioid histologic type and early-stage disease were 140 (86.4%) and 109 (67.3%), respectively. ProMisE classification assigned 48 (29.6%), 16 (9.9%), 72 (44.4%), and 26 (16.0%) patients to MMR-deficient, POLE-mutated, p53 wild-type, and p53 abnormal subgroups, respectively. L1CAM was identified as an independent poor prognostic factor for progression-free survival (PFS; adjusted hazard ratio [aHR], 3.207; 95% confidence interval (CI), 1.432-7.187; P = 0.005), whereas β-catenin and PD-L1 positivity were not associated with recurrence (P = 0.462 and P = 0.152, respectively). In p53 wild-type subgroup, L1CAM positivity was associated with worse PFS (aHR, 4.906; 95% CI, 1.685-14.287; P = 0.004)., Conclusion: L1CAM positivity was associated with poor prognosis in EC and further stratified the risk of recurrence in p53 wild-type subgroup, whereas β-catenin and PD-L1 were not informative for risk stratification., Competing Interests: Declaration of Competing Interest The authors declare no competing interest relevant to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Endometrial carcinosarcoma is a rare and aggressive high-grade endometrial carcinoma with secondary sarcomatous trans-differentiation (conversion theory). The clinical presentation and diagnostic work-up roughly align with those of the more common endometrioid counterpart, although endometrial carcinosarcoma is more frequently diagnosed at an advanced stage. Endometrial carcinosarcoma is not a single entity but encompasses different histological subtypes, depending on the type of carcinomatous and sarcomatous elements. The majority of endometrial carcinosarcomas are characterized by p53 abnormalities. The proportion of POLE and microsatellite instablity-high (MSI-H) is directly related to the epithelial component, being approximately 25% and 3% in endometrioid and non-endometrioid components.The management of non-metastatic disease is based on a multimodal approach with optimal surgery followed by (concomitant or sequential) chemotherapy and radiotherapy, even for early stages. Palliative chemotherapy is recommended in the metastatic or recurrent setting, with carboplatin/paclitaxel doublet being the first-line regimen. Although the introduction of immunotherapy plus/minus a tyrosine kinase inhibitor shifted the paradigm of treatment of patients with recurrent endometrial cancer, patients with endometrial carcinosarcoma were excluded from most studies evaluating single-agent immunotherapy or the combination. However, the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) approved the use of pembrolizumab and lenvatinib in endometrial cancer (all histotypes) after progression on chemotherapy and single-agent immunotherapy in MSI-H cancers. In the era of precision medicine, emerging knowledge on molecular endometrial carcinosarcoma is opening new promising therapeutic options for more personalized treatment. The present review outlines state-of-the-art knowledge and future directions for patients with endometrial carcinosarcoma., Competing Interests: Competing interests: GB: Novartis AG Pharma (C/A, H), Italian Ministry of Health (RG); NC: AstraZeneca (C/A, SH), Seattle Genetics (C/A, SH), MSD (SAB), Mersana (C/A, SH), eTheRNA immunotherapies NV (C/A, SH), Roche (travel expenses), Genmab (travel expenses), Amgen (travel expenses). IR-C: honoraria from AstraZeneca, Clovis, GSK/Tesaro, and PharmaMar; consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro, Genmab, PharmaMar, MSD, Mersana, Deciphera, OncXea, Esai, BMS, Novartis, and Pfizer; research funding from MSD; travel expenses from AstraZeneca, GSK, and Roche. YS: AstraZeneca (CA), GSK (CA). PW: Amgen (SH, RF, SAB), AstraZeneca (SH, RF, H, SAB), Clovis (SH, RF, SAB), Eisai (SH, SAB), GSK (SH, SAB), Lilly (SH, SAB), MSD (SH, RF, SAB), Novartis (SH, RF, SAB), Pfizer (SH, RF, SAB), Roche (SH, RF, H, SAB), TEVA (SH, SAB). NYLN: AstraZeneca (SH), Janssen (SH). KT: AstraZeneca (SH), Chugai (SH, RF), Eisai (SH), MSD (SH), Mochida (SH), Takeda (SH). TE: Takeda (SH), Astra Zeneca (SH), Eisai (SH), Chugai Pharma (SH, RF), MSD (SH), Mochida (SH). DL: AstraZeneca (H, CA), Clovis (H, CA, RF), GSK/Tesaro (H, CA), Roche (CA), Genmab (CA), PharmaMar (CA, RF), MSD (CA, RF), Esai (CA), Merck Serono (CA), Novartis (CA), and PharmaMar (H); consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro. DMP: AstraZeneca (CA, SH, SAB), GSK (CA, SH, SAB). NRA-R: NIH/NCI Cancer Center support grant P30 CA008748 (F). HD: Roche (CA, SH, SAB), Pfizer (CA, SH, SAB), AstraZeneca (SH, SAB), Lily (SAB), GSK (SAB), Novartis (SH), Pharmamar (SH); BJM: AstraZeneca (SH, SAB), GSK (SH, SAB), Incyte (SAB), Merck (SH, SAB), Roche/Genentech (SH, SAB), Eisai (SAB), GOG-Foundation (E), US Oncology (E)., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The mainstay of endometrial cancer treatment is surgical resection of tumors and postoperative adjuvant treatment is recommended if necessary. However, there is no consensus on the management of unresectable metastatic endometrial cancer. This study aimed to assess the feasibility and effectiveness of neoadjuvant chemotherapy followed by interval debulking surgery (NAC-IDS) in unresectable, metastatic endometrial cancer., Methods: From the endometrial cancer cohorts of four institutions in Korea, we identified patients with International Federation of Gynecology and Obstetrics stages IIIC-IVB endometrial cancer who received NAC-IDS between January 2008 and December 2020. Through a medical record review, we collected patients' clinicopathological data. Progression-free survival (PFS), overall survival (OS), and the factors affecting survival outcomes were analyzed., Results: Overall, 32 patients were included with endometrioid (n = 18), serous (n = 5), carcinosarcoma (n = 6), and other histological types (n = 3). Among them, 28 (87.5%) patients had stage IVB disease. The most common neoadjuvant chemotherapy (NAC) regimen was paclitaxel-carboplatin (n = 25, 78.1%), which was administered for a median of six cycles. While 26 (81.3%) patients showed an objective response, two (6.3%) progressed despite NAC. At the time of interval debulking surgery (IDS), 23 (71.9%) patients achieved complete cytoreduction. During 31.0 months of the median follow-up, there were 23 recurrences and 11 deaths, corresponding to a median PFS of 19.7 months and a 3-year OS rate of 69.7%. In multivariate analyses, non-endometrioid histology and residual tumor after IDS were identified as independent poor prognostic factors for PFS (adjusted hazard ratio [HR], 7.322; P < 0.001 and 5.934; P = 0.001, respectively). Multivariate analysis for OS could not be conducted because of the small number of events, although non-endometrioid histology was the only factor associated with worse OS in univariate analysis (adjusted HR, 4.523; P = 0.032)., Conclusions: NAC-IDS may be a treatment option for unresectable metastatic endometrial cancer. Tumor histology and the possibility of complete cytoreduction are the primary considerations for NAC-IDS., (© 2022. The Author(s).)

Objective: To investigate the effectiveness and safety of pembrolizumab and lenvatinib (PEMBRO+LEN) for recurrent endometrial cancer (EC) in a real-world setting., Methods: This multicenter retrospective cohort study included patients with recurrent EC who received PEMBRO+LEN between March 2020 and May 2021 at three tertiary hospitals in Korea. We summarized patient characteristics and evaluated the response rates, survival outcomes, and treatment-related adverse events (AEs)., Results: In total, 48 patients were included in the study. The median age of the patients was 62.5 (range, 42-78) years. The most common histologic subtype was endometrioid adenocarcinoma (43.8%), followed by serous adenocarcinoma (25.0%). Most patients (91.7%) had mismatch repair-proficient tumors. Patients received PEMBRO+LEN for a median of 4.5 cycles, during which the best objective response rate and disease control rate were 23.8% (95% CI, 11.9-38.1) and 76.2% (95% CI, 61.9-88.1), respectively. Overall, 56.2% of patients experienced LEN dose reduction once or more and 16.7% experienced LEN interruption. The most common treatment-related AEs were fatigue (18.8%), hypertension (16.7%), and hypothyroidism (14.6%). Total of 8 patients (16.7%) discontinued LEN during the treatment because of treatment-related AEs. Serum CA-125 level was the only prognostic factor for progression-free survival (adjusted hazard ratio, 4.41; 95% confidence interval, 1.19-16.36; p = 0.03)., Conclusions: In our real-world study, Korean patients with recurrent EC who received PEMBRO+LEN showed lower treatment response rate and similar treatment discontinuation rate, compared to clinical trials., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Clear cell endometrial carcinoma represents an uncommon and poorly understood entity. Data from molecular/genomic profiling highlighted the importance of various signatures in assessing the prognosis of endometrial cancer according to four classes of risk (POLE mutated, MMRd, NSMP, and p53 abnormal). Unfortunately, data specific to clear cell histological subtype endometrial cancer are lacking. More recently, data has emerged to suggest that most of the patients (more than 80%) with clear cell endometrial carcinoma are characterized by p53 abnormality or NSMP type. This classification has important therapeutic implications. Although it is an uncommon entity, clear cell endometrial cancer patients with POLE mutation seem characterized by a good prognosis. Chemotherapy is effective in patients with NSMP (especially in stage III and IV) and patients with p53 abnormal disease (all stages). While, preliminary data suggested that patients with MMRd are less likely to benefit from chemotherapy. The latter group appears to benefit much more from immune checkpoint inhibitors: recent data from clinical trials on pembrolizumab plus lenvatinib and nivolumab plus cabozantinib supported that immunotherapy plus tyrosine kinase inhibitors (TKI) would be the most appropriate treatment for recurrent non-endometrioid endometrial cancer (including clear cell carcinoma) after the failure of platinum-based chemotherapy. Moreover, ongoing clinical trials testing the anti-tumor activity of innovative products will clarify the better strategies for advanced/recurrent clear cell endometrial carcinoma. Further prospective evidence is urgently needed to better characterize clear cell endometrial carcinoma., Competing Interests: Declaration of Competing Interest Giorgio Bogani: Novartis AG Pharma (C/A, H), Italian Ministry of Health (RG). Nicole Concin: AstraZeneca (C/A, SH), Seattle Genetics (C/A, SH), MSD (SAB), Mersana (C/A, SH), eTheRNA immunotherapies NV (C/A, SH), Roche (travel expenses), Genmab (travel expenses), Amgen (travel expenses). Isabelle Ray-Coquard: Honoraria from AstraZeneca, Clovis, GSK/Tesaro and PharmaMar; Consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro, Genmab, PharmaMar, MSD, Mersana, Deciphera, OncXea, Esai, BMS, Novartis and Pfizer; Research funding from MSD;Travel expenses from AstraZeneca, GSK and Roche. Yakir Segev: AstraZeneca (CA), GSK (CA). Pauline Wimberger: Amgen (SH, RF, SAB), AstraZeneca (SH, RF, H, SAB), Clovis (SH, RF, SAB), Eisai (SH, SAB), GSK (SH, SAB), Lilly (SH, SAB), MSD (SH, RF, SAB), Novartis (SH, RF, SAB), Pfizer (SH, RF, SAB), Roche (SH, RF, H, SAB), TEVA (SH, SAB). Natalie YL Ngoi: AstraZeneca (SH), Janssen (SH). Kazuhiro Takehara: AstraZeneca (SH), Chugai (SH, RF), Eisai (SH), MSD (SH), Mochida (SH), Takeda (SH). Takayuki Enomoto: Takeda (SH), Astra Zeneca (SH), Eisai (SH), Chugai Pharma (SH, RF), MSD (SH), Mochida (SH). Domenica Lorusso: AstraZeneca (H, CA), Clovis (H, CA, RF), GSK/Tesaro (H, CA), Roche (CA), Genmab (CA), PharmaMar (CA, RF), MSD (CA, RF), Esai (CA), Merck Serono (CA), Novartis (CA) and PharmaMar (H); Consulting/advisory board fees from AstraZeneca, Roche, Clovis, GSK/Tesaro. Diane Provencher: AstraZeneca (CA, SH, SAB), GSK (CA, SH, SAB). Nadeem Abu-Rustum: NIH/NCI Cancer Center Support Grant P30 CA008748 (F). Hannelore Denys: Roche (CA, SH, SAB), Pfizer (CA, SH, SAB), AstraZeneca (SH, SAB), Lily (SAB), GSK (SAB), Novartis (SH), Pharmamar (SH). Bradley J Monk: AstraZeneca (SH, SAB), GSK (SH, SAB), Incyte (SAB), Merck (SH, SAB), Roche/Genentech (SH, SAB), Eisai (SAB), GOG-Foundation (E), US Oncology (E). The other authors indicated no financial relationship. Legend: consulting/advisory relationship (CA); speaker honoraria (SH); honoraria (H); research funding (RF); ownership interest (OI); intellectual propriety/patent holder (IP); scientific advisory board (SAB)., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: The impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident., Primary Objective: Evaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence., Study Hypothesis: Comprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65., Trial Design: Open label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended., Major Inclusion Criteria: Patients with histologically confirmed endometrial cancer stages pT1b-pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible., Exclusion Criteria: Patients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease., Primary Endpoint: Overall survival calculated from the date of randomization until death., Sample Size: 640 patients will be enrolled in the study., Estimated Dates for Completing Accrual and Presenting Results: At present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031., Trial Registration: NCT03438474., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma., Patients and Methods: A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33-based high-intermediate-risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m 2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles., Results: The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated., Conclusion: Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

Objective: To evaluate the efficacy of combined oral medroxyprogesterone acetate (MPA)/levonorgestrel-intrauterine system (LNG-IUS) treatment and to compare the diagnostic accuracy of endometrial aspiration biopsy with dilatation & curettage (D&C) in young women with early-stage endometrial cancer (EC) who wished to preserve their fertility., Methods: A prospective phase II multicenter study was conducted from January 2012 to January 2017. Patients with grade 1 endometrioid adenocarcinoma confined to the endometrium were treated with combined oral MPA (500 mg/day)/LNG-IUS. At 3 and 6 months of treatment, the histologic change of the endometrial tissue was assessed. The regression rate at 6 months treatment and the consistency of the histologic results between the aspiration biopsy and the D&C were evaluated., Results: Forty-four patients were enrolled. Nine voluntarily withdrew and 35 patients completed the protocol treatment. The complete regression (CR) rate at 6 months was 37.1% (13/35). Partial response was shown in 25.7% of cases (9/35). There were no cases of progressive disease and no treatment-related complications. A comparison of the pathologic results from aspiration biopsy and D&C was carried out for 33 cases. Fifteen cases were diagnosed as "EC" by D&C. Among these, only 8 were diagnosed with EC from aspiration biopsy, yielding a diagnostic concordance of 53.3% (κ=0.55)., Conclusion: Combined oral MPA/LNG-IUS treatment for EC showed 37.1% of CR rate at 6 months. Considering the short treatment periods, CR rate may be much higher if the treatment continued to 9 or 12 months. So, this treatment is still a viable treatment option for young women of early-stage EC. Endometrial aspiration biopsy with the LNG-IUS in place is less accurate than D&C for follow-up evaluation of patients undergoing this treatment., Trial Registration: ClinicalTrials.gov Identifier: NCT01594879., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Objective: To investigate the incidence and trends of cervical (C53), endometrial (C54.1), and ovarian cancer (C56) among Korean females between 1999 and 2015., Methods: The incidence of the three major gynecological cancers between 1999 and 2015 was analyzed based on the data from the Korea Central Cancer Registry. The age-standardized rates (ASRs) and the annual percent changes (APCs) for each site were calculated., Results: The absolute incidence rates of the three major gynecological cancers increased from 6,394 in 1999 to 8,288 in 2015. ASR for gynecologic cancer decreased from 23.7 per 100,000 in 1999 to 21.1 in 2015. This was mainly due to a definitive decrease in the incidence of cervical cancer, which recorded an APC of -3.7%. The trends of APC for gynecologic cancer were variable, being -1.36% between 1999 and 2006 and -0.11% between 2006 and 2015. A definitive but variable increase was noted for endometrial cancer, and the APC for this cancer was 7.4% between 1999 and 2009 and 3.5% between 2009 and 2015. The incidence of ovarian cancer gradually increased, with an APC of 1.8% between 1999 and 2015., Conclusion: Overall, ASRs and APCs for the three major gynecological cancers are decreasing, with a recent reduction in the width of the change. However, there has been a progressive increase in the incidence of endometrial and ovarian cancers., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2019. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

Background: Somatic amplifications of the LYL1 gene are relatively common occurrences in patients who develop uterine corpus endometrial carcinoma (UCEC) as opposed to other cancers. This study was undertaken to determine whether such genetic alterations affect survival outcomes of UCEC., Methods: In 370 patients with UCEC, we analysed clinicopathologic characteristics and corresponding genomic data from The Cancer Genome Atlas database. Patients were stratified according to LYL1 gene status, grouped as amplification or non-amplification. Heightened levels of cancer-related genes expressed in concert with LYL1 amplification were similarly investigated through differentially expressed gene and gene set enrichment analyses. Factors associated with survival outcomes were also identified., Results: Somatic LYL1 gene amplification was observed in 22 patients (5.9%) with UCEC. Patients displaying amplification (vs. non-amplification) were significantly older at the time of diagnosis and more often were marked by non-endometrioid, high-grade, or advanced disease. In survival analysis, the amplification subset showed poorer progression-free survival (PFS) and overall survival (OS) rates (3-year PFS: 34.4% vs. 79.9%, P = 0.031; 5-year OS: 25.1% vs. 84.9%, P = 0.014). However, multivariate analyses adjusted for tumor histologic type, grade, and stage did not confirm LYL1 gene amplification as an independent prognostic factor for either PFS or OS. Nevertheless, MAPK, WNT, and cell cycle pathways were significantly enriched by LYL1 gene amplification (P < 0.001, P = 0.002, and P = 0.004, respectively)., Conclusions: Despite not being identified as an independent prognostic factor in UCEC, LYL1 gene amplification is associated with other poor prognostic factors and correlated with upregulation of cancer-related pathways.

Purpose: To determine whether the relative metabolic activity of pelvic or para-aortic LN compared with that of primary tumor measured by preoperative [ 18 F]FDG PET/CT scan has prognostic value in patients with endometrioid endometrial carcinoma., Methods: We retrospectively reviewed patients with endometrioid endometrial carcinoma who underwent preoperative [ 18 F]FDG PET/CT scans. Prognostic values of PET/CT-derived metabolic variables such as maximum standardized uptake value (SUV) of the primary endometrial carcinoma (SUV Tumor ) and LN (SUV LN ), and the LN-to-endometrial carcinoma SUV ratio (SUV LN / SUV Tumor ) were assessed., Results: Clinico-pathological data, imaging data, and treatment results were reviewed for 107 eligible patients. Median post-surgical follow-up was 23 months (range, 6-60), and 7 (6.5%) patients experienced recurrence. Regression analysis showed that SUV LN / SUV Tumor (P < 0.001), SUV LN (P = 0.003), International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.006), and tumor grade (P = 0.011) were risk factors of recurrence. Multivariate regression analysis revealed that FIGO stage (P = 0.034) was the independent risk factor of recurrence. SUV LN / SUV Tumor showed significant correlation with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), recurrence (P = 0.001), tumor grade (P < 0.001), and deep myometrial invasion of tumor (P = 0.022). Patient groups categorized by SUV LN / SUV Tumor showed significant difference in progression-free survival (Log-rank test, P = 0.001)., Conclusions: Preoperative SUV LN / SUV Tumor measured by [ 18 F]FDG PET/CT was significantly associated with recurrence, and may become a novel prognostic factor in patients with endometrioid endometrial carcinoma.

Objective: The aim of this article was to identify current practice patterns of care in the surgical and adjuvant management of endometrial cancer in East Asia (Korea, Japan, China, and Taiwan) METHODS: A validated 20-item questionnaire on surgical and adjuvant procedures for endometrial cancer was sent to active members of the Gynecologic Oncology Group from 4 East Asian countries. Data were collected using an Internet survey database., Results: A total of 376 members from Korea (n = 108), Japan (n = 140), China (n = 51), and Taiwan (n = 77) responded to the survey. With respect to early-stage endometrial cancer, laparotomy (57.7%) was the most preferred mode of surgery in Japan, whereas laparoscopy was the most common in the remaining 3 countries. For patients with presumed stage IA/G1 disease, approximately 65% of respondents favored systematic lymphadenectomy. For patients with presumed stage IB disease, most respondents stated that systematic lymphadenectomy should be performed (92.6% for stage IBG1, 95.8% for stage IBG3). Meanwhile, the extents of lymphadenectomy differed among countries (P < 0.001). Considerable agreement was noted between countries regarding indications for adjuvant therapy for stage IIIA or IIIC1 disease, whereas the preferred options for adjuvant therapy varied according to country (P < 0.001). Specifically, chemotherapy was the most common selection option in Japan, whereas concurrent chemoradiotherapy was preferred in the other countries., Conclusions: Considerable agreement was identified with respect to the necessity for lymphadenectomy for surgical staging and the indications for adjuvant therapy. However, extents of surgery and preferred adjuvant treatment options for endometrial cancer varied widely between countries.

Objective: To evaluate the influence of body weight change during fertility-sparing progestin therapy on oncologic and reproductive outcomes in young women with early-stage endometrial cancer who did not complete child bearing., Methods: This multicenter, retrospective study included 154 young patients with well-differentiated, endometrium-confined endometrioid endometrial adenocarcinoma on magnetic resonance imaging who received fertility-sparing progestin therapy., Results: The mean body weight and body mass index (BMI) at baseline and progestin therapy completion was 65.3±16.2 and 66.5±15.9kg (P=0.044), respectively, and 25.51±5.99 and 25.99±5.94kg/m 2 (P=0.034), respectively. During progestin therapy, 51 (33.1%), 29 (18.8%), and 74 patients (48.1%) had weight loss, no weight change, and weight gain, respectively, of which 11 (7.1%) had 10% weight loss and 30 (19.5%) had 10% weight gain. A pretreatment BMI of ≥25kg/m 2 was significantly associated with a lower complete response rate to progestin therapy (P=0.003) and a high recurrence rate (P=0.033). A posttreatment BMI of ≥25kg/m 2 was also a significant factor for high recurrence rate (P=0.049). However, weight change during therapy was not significantly associated with complete response or recurrence rate. Pre and posttreatment BMIs and weight change were not associated with pregnancy and live birth rates., Conclusion: Weight change during progestin therapy has little influence on complete response, recurrence, pregnancy, and live birth rates. However, pre and posttreatment BMIs of ≥25kg/m 2 were significant predictors for poor treatment response and high recurrence. Therefore, it is important to maintain patients' normal BMIs during progestin therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Debate on the value of lymphadenectomy continues in endometrial cancer. The aim of this study was to investigate patient and clinician preferences for routine lymphadenectomy versus no lymphadenectomy in the surgical management of endometrial cancer., Methods: A discrete choice experiment and trade-off question were designed and distributed to 103 endometrial cancer patients and 90 gynecologic oncologists. Participant preferences were quantified with regression analysis using scenarios based on three attributes: 5-year progression-free survival and the rates of acute and chronic complication. A trade-off technique varying the risk of recurrence for no lymphadenectomy was used to quantify any additional risk of recurrence that these participants would accept to receive no lymphadenectomy instead of routine lymphadenectomy., Results: On the basis of discrete choice experiment, the recurrence rate and lymphedema risk had a statistically significant impact on respondents' preference. The trade-off question showed that the median additional accepted risk of having no lymphadenectomy was 2.8% for gynecologic oncologists (0.5-14%) and 3.0% for patients (0.5-10%), but this difference was not significant (p = 0.620). Patients who were younger or had a higher education level or no history of delivery or shorter duration since diagnosis were prepared to accept higher additional risks of having no lymphadenectomy., Conclusions: Our results show that the majority of endometrial cancer patients and clinicians will accept a small amount of recurrence risk to reduce the incidence of lymphedema. Regarding preference heterogeneity among patients, our results show that it is important for surgeons to take a patient-tailored approach when discussing surgical management.

Background: Previously proposed criteria for preoperatively identifying endometrial cancer patients at low risk for lymph node metastasis remain to be verified. For this purpose, a prospective, multicenter observational study was performed., Methods: Eligible patients with histologically confirmed endometrial cancer underwent magnetic resonance imaging (MRI) and serum cancer antigen 125 (CA 125) testing before surgery. The following criteria were used to identify low-risk patients: 1) endometrioid-type cancer, 2) no evidence of deep myometrial invasion on MRI, 3) no enlarged lymph nodes on MRI, 4) no suspicious metastasis out of the uterine corpus, and 5) serum CA 125 levels less than 35 U/mL. Systematic pelvic and/or para-aortic lymphadenectomy was performed for all patients. The primary endpoint was estimation of the negative predictive value (NPV)., Results: From January 2012 to December 2014, 529 patients from 20 hospitals in 3 Asian countries were consecutively enrolled. According to our criteria, 272 patients (51.4%) were categorized into the low-risk group. Fifty-three of the 529 patients (10.0%) had lymph node metastases; these patients included 8 (2.9%) falsely categorized as low-risk. The sensitivity and specificity of the criteria were 84.9% and 55.5%, respectively. The NPV of 97.1% was higher than the predefined target endpoint of 96%., Conclusions: The low-risk criteria based on preoperative tests were confirmed to be reliable and accurate for identifying patients at low risk for lymph node metastasis. These criteria may facilitate patient counseling and surgical decision making. Cancer 2017;123:263-272. © 2016 American Cancer Society., (© 2016 American Cancer Society.)

Clinical practice guidelines for gynecologic cancers have been developed by many organizations. Although these guidelines have much in common in terms of the practice of standard of care for uterine corpus cancer, practice guidelines that reflect the characteristics of patients and healthcare and insurance systems are needed for each country. The Korean Society of Gynecologic Oncology (KSGO) published the first edition of practice guidelines for gynecologic cancer treatment in late 2006; the second edition was released in July 2010 as an evidence-based recommendation. The Guidelines Revision Committee was established in 2015 and decided to produce the third edition of the guidelines as an advanced form based on evidence-based medicine, considering up-to-date clinical trials and abundant qualified Korean data. These guidelines cover screening, surgery, adjuvant treatment, and advanced and recurrent disease with respect to endometrial carcinoma and uterine sarcoma. The committee members and many gynecologic oncologists derived key questions from the discussion, and a number of relevant scientific literatures were reviewed in advance. Recommendations for each specific question were developed by the consensus conference, and they are summarized here, together with other details. The objective of these practice guidelines is to establish standard policies on issues in clinical areas related to the management of uterine corpus cancer based on the findings in published papers to date and the consensus of experts as a KSGO Consensus Statement., Competing Interests: Jae-Weon Kim serves as editors of the Journal of Gynecologic Oncology (JGO), but have no role in the decision to publish this article. No other conflict of interest relevant to this article was reported.

Objective: The aim of this study was to evaluate the value of vaginal cytology, imaging modalities, and serum CA-125 in detecting asymptomatic recurrence during posttreatment surveillance for early-stage endometrial cancer., Methods: A retrospective analysis was conducted on patients with stage I to II endometrial cancer who received primary surgical treatment at Seoul National University Hospital between 2000 and 2011. Clinicopathologic characteristics and surveillance test data were obtained from medical records. The total numbers of vaginal cytologies, imaging studies, and serum CA-125 levels performed during surveillance or until recurrence were evaluated, and the number of tests needed to detect each asymptomatic recurrence was calculated., Results: A total of 389 patients were identified, together with a total of 3323 vaginal cytologies, 1025 chest x-rays, 1177 abdominal computed tomography (CT) scans, 98 magnetic resonance imaging scans, 163 positron emission tomography/CT scans, 298 ultrasonographies, and 3335 serum CA-125 results obtained during the surveillance period. Recurrence was detected in 14 patients (3.6%). Ten of these cases were asymptomatic, of which six were identified through CT scans and four were identified through elevated serum CA-125 levels. Most of the patients (7/10) with asymptomatic recurrences had localized recurrence patterns, five of whom underwent curative-intent resection and survived. The number of CA-125 tests needed to identify 1 asymptomatic recurrence was 839, whereas the number of CT scans needed to achieve the same result was 196. Other imaging modalities and vaginal cytology did not detect asymptomatic recurrence., Conclusions: For posttreatment surveillance in early-stage endometrial cancer, vaginal cytology and imaging modalities such as chest x-ray, magnetic resonance imaging, positron emission tomography/CT, and ultrasonography have low utility. Routine CT scans and serum CA-125 testing may be useful for detecting asymptomatic recurrence.

Objective: To identify current practice patterns for unresolved issues in the surgical and adjuvant management of endometrial cancer in Korea., Methods: We designed and conducted a survey of all 218 active members of the Korean Gynecologic Oncology Group to try to identify how they would manage various case scenarios for endometrial cancer. Data were collected using an Internet survey database., Results: A total of 108 members (49.5%) responded to the survey. Laparoscopy (81.6%) was the most commonly used mode of surgery in early-stage endometrial cancer. Of all the respondents, 19.8% stated that lymphadenectomy could be omitted and 21.7% recommended selective lymphadenectomy based on sentinel biopsy or frozen results for patients with presumed stage IA/grade 1 disease. On the other hand, 71.9% of respondents recommended para-aortic lymphadenectomy for patients with presumed stage IB/grade 1 disease and 86.4% recommended this treatment for presumed stage IB/grade 3 disease. The majority of respondents performed adjuvant therapy for stage IB/grade 2 (91.7%), IB/grade 3 (99.0%), and stage II (89.6%). Whole pelvic radiotherapy and vaginal brachytherapy were the most frequently used options among these patients. All respondents administered adjuvant therapy when node metastasis was found, and concurrent chemoradiotherapy (53.2%) was the most preferred option for stage IIIC1 disease., Conclusion: There is broad variation in both the surgical and adjuvant treatment of endometrial cancer among Korean gynecologic oncologists.

Objective: The aim of this study was to determine the cost-effectiveness of selective lymphadenectomy using a preoperative prediction model compared to routine lymphadenectomy for patients undergoing surgery for endometrial cancer in the US and Korea., Methods: We used a modified Markov model to estimate clinical and economic outcomes for newly diagnosed, apparent early-stage endometrial cancer patients under two different strategies: (1) selective lymphadenectomy, where patients classified as low risk based on the preoperative prediction model did not undergo complete surgical staging, and (2) routine lymphadenectomy, where all patients underwent complete surgical staging. Published data were used to estimate the rates of adjuvant therapy and survival. Costs were calculated from the perspective of US or Korean payers. Cost-effectiveness ratios were analyzed separately using data from each country., Results: Base-case analysis indicated that selective lymphadenectomy was less costly ($6454 vs. $7079 in Korea; $23,995 vs. $26,318 in the US) and more effective (6.91 quality-adjusted life years (QALYs) vs. 6.85 QALYs in Korea; 6.87 QALYs vs. 6.81 QALYs in the US) than routine lymphadenectomy in both countries. This result was robust in a deterministic sensitivity analysis, with the exception of when the utility scores for patients with lymphedema were varied. So long as a modest preference for avoiding lymphedema (disutility of 0.04) was obtained, selective lymphadenectomy remained the dominant strategy., Conclusions: A selective lymphadenectomy strategy based on a preoperative prediction model was shown to be more cost-effective than routine lymphadenectomy for endometrial cancer patients in the US and Korea., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to determine whether knowledge of lymph node status improves survival prediction in clinically early-stage endometrial cancer., Methods: The records of 661 patients with apparently uterine-confined disease were reviewed. The performance in predicting overall survival and cause-specific survival was compared between a multivariate prognostic model with nodal status and a model without nodal status by calculating Harrell concordance index., Results: Among 661 patients with clinically early-stage endometrial cancer, the lymph node metastasis rate was 8.3% (55/661). Lymph node metastasis independently associated with cause-specific survival only when no stratification according to adjuvant treatment was applied (P = 0.035). After stratification according to adjuvant radiotherapy, lymph node status marginally associated with cause-specific survival (P = 0.073), whereas myometrial invasion retained its strong association with cause-specific survival (P < 0.001). However, there was no significant difference in the performance of the survival model using only uterine factors and the model using lymph node status and uterine factors (concordance index, 0.77 vs 0.77, respectively; P = 0.798)., Conclusions: Knowledge of lymph node status did not significantly improve the performance of survival prediction in apparently uterine-confined endometrial cancer, although it was independently associated with survival. In the patients with clinically early-stage endometrial cancer, the accuracy of the prediction of survival was comparable between risk grouping without lymph node status and that including lymph node status.

Purpose: Using integrated PET/CT, we evaluated the prognostic relevance of preoperative pelvic lymph node (LN) (18)F-FDG uptake in endometrioid endometrial cancer., Methods: We retrospectively reviewed patients with pathologically proven endometrial cancer who underwent preoperative (18)F-FDG PET/CT scans to evaluate the prognostic significance of PET/CT parameters and other clinicopathological variables. We used Cox proportional hazards regression to examine the relationship between recurrence and the maximum standardized uptake value (SUVmax) in pelvic LNs (SUVLN) on FDG PET/CT., Results: Clinical data, treatment modalities and results were reviewed in 70 eligible patients. The median postsurgical follow-up was 29 months (range 6 to 95 months). Receiver-operating characteristic analysis identified the significant SUVLN cut-off value as 15. The SUVLN correlated with FIGO stage (P < 0.001), LN metastasis (P < 0.001), lymphovascular space invasion (P < 0.001), SUVtumour (P = 0.001), metastatic LN size (P = 0.004), primary tumour size (P = 0.012), tumour grade (P = 0.015) and depth of tumour invasion (P = 0.035). Regression analysis showed a statistically significant association between recurrence and SUVLN (P = 0.002). Recurrence differed significantly (P < 0.001) between patients with SUVLN >15 and those with SUVLN ≤15., Conclusion: Preoperative pelvic LN FDG uptake exhibited a strong significant association with recurrence of endometrioid endometrial cancer.

Background: Comprehensive surgical staging plays an important role in apparent early-stage epithelial ovarian cancer (eEOC). However, few studies have evaluated how often upstaging occurs solely as a result of microscopic metastases identified from omentectomy and random peritoneal biopsies. The purpose of this study was to evaluate the significance of omentectomy and random peritoneal biopsies for normal-appearing tissues in eEOC., Methods: A retrospective study was performed of patients with eEOC [International Federation of Gynecology and Obstetrics (FIGO) Stages I-IIIA] between 1991 and 2010. The demographic characteristics, surgical findings, and pathologic variables were analyzed., Results: In total, 324 patients were included in the study. Of 127 patients who underwent random peritoneal biopsies, 6 (4.7 %) were upstaged to IIB or IIC based solely on pelvic peritoneal biopsy findings and 3 (2.4 %) were upstaged to IIIA based on abdominal peritoneal biopsy findings. Of 256 patients who underwent omentectomy, 7 (2.7 %) were upstaged to IIIA based on microscopic metastases identified in the normal-appearing omentum. Following routine omentectomy and random peritoneal biopsies, only one patient in our cohort experienced a change in her adjuvant treatment recommendation., Conclusions: Although the rate of upstaging based on routine omentectomy and random peritoneal biopsies is not negligible, there is a low chance that the treatment plan will be altered to include chemotherapy after surgery as a result of the occult microscopic metastases identified.

Objective: We compared the impact of positive peritoneal cytology on prognosis between patients with endometrioid and non-endometrioid endometrial carcinoma., Methods: We retrospectively reviewed the medical records of 490 patients diagnosed with endometrial cancer between 2000 and 2012. These patients were divided into two groups: endometrioid and non-endometrioid histologies. We compared the patients' baseline characteristics, tumor recurrence patterns, and survival to determine the prognostic factors and how they differed between the two groups., Results: Of the included patients, 448 had endometrioid histology and 42 had non-endometrioid histology. A total of 27 patients experienced tumor recurrence: 17 with endometrioid histology (4.0%) and 10 with non-endometrioid histology (23.8%). Compared to endometrioid type, non-endometrioid type exhibited higher rates of recurrence (p<0.01). Recurrence sites of the non-endometrioid group were mainly peritoneal seeding (p<0.01) and distant organ metastasis (p=0.02). Risk factors for tumor recurrence included patient age, stage of disease, and adjuvant treatment for endometrioid type. On the other hand, in cases of non-endometrioid endometrial cancer, positive peritoneal cytology was an independent prognostic factor regardless of tumor stage (HR, 15.34; 95% CI, 3.55-66.25; p<0.01). Among cases with non-endometrioid histology, median recurrence-free survival significantly differed between the negative peritoneal cytology group and the positive peritoneal cytology group (120 months versus 22 months, respectively; p<0.01)., Conclusions: Positive peritoneal cytology is an independent prognostic factor for patients with non-endometrioid endometrial cancer., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to develop a Web-based nomogram for predicting the individualized risk of para-aortic nodal metastasis in incompletely staged patients with endometrial cancer., Methods: From 8 institutions, the medical records of 397 patients who underwent pelvic and para-aortic lymphadenectomy as a surgical staging procedure were retrospectively reviewed. A multivariate logistic regression model was created and internally validated by rigorous bootstrap resampling methods. Finally, the model was transformed into a user-friendly Web-based nomogram (http://http://www.kgog.org/nomogram/empa001.html)., Results: The rate of para-aortic nodal metastasis was 14.4% (57/397 patients). Using a stepwise variable selection, 4 variables including deep myometrial invasion, non-endometrioid subtype, lymphovascular space invasion, and log-transformed CA-125 levels were finally adopted. After 1000 repetitions of bootstrapping, all of these 4 variables retained a significant association with para-aortic nodal metastasis in the multivariate analysis-deep myometrial invasion (P = 0.001), non-endometrioid histologic subtype (P = 0.034), lymphovascular space invasion (P = 0.003), and log-transformed serum CA-125 levels (P = 0.004). The model showed good discrimination (C statistics = 0.87; 95% confidence interval, 0.82-0.92) and accurate calibration (Hosmer-Lemeshow P = 0.74)., Conclusions: This nomogram showed good performance in predicting para-aortic metastasis in patients with endometrial cancer. The tool may be useful in determining the extent of lymphadenectomy after incomplete surgery.

Objective: The aim of this study was to evaluate the impact of ovarian preservation on the recurrence and survival rates of premenopausal women with early-stage endometrial cancer., Methods: Using medical records of premenopausal women who received primary surgical treatment for stage I-II endometrial cancer, the demographics and survival rates were compared retrospectively for patients who had ovarian preservation and those who underwent bilateral salpingo-oophorectomy. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were performed to adjust for selection bias between the two groups., Results: A total of 495 women were identified, including 176 patients who had ovarian preservation. The ovarian preservation group was younger (P<0.001) and had an earlier year of diagnosis (P=0.014), a lower prevalence of lymphadenectomy (P<0.001), and a marginally significant association with lower tumor grade (P=0.052). The Kaplan-Meier curve and the log rank test showed no difference in either recurrence-free survival (P=0.742) or overall survival (P=0.462) between the two groups. In a multivariate Cox model adjusted by IPTW and covariates, ovarian preservation had no effect on either recurrence (hazard ratio [HR], 0.73; 95% CI, 0.29-1.81) or overall survival (HR, 1.33; 95% CI, 0.43-4.09)., Conclusions: Ovarian preservation does not appear to be associated with an adverse impact on the outcomes of premenopausal women with early-stage endometrial cancer. The present study has useful implications for physicians counseling young women who want to preserve their ovaries., (© 2013.)

Objective: The aim of this study was to elucidate the significance of tumor volume as a risk factor for predicting lymph node metastasis., Methods: We applied the tumor volume index to the data that were collected for 327 Korean patients with endometrial cancer who underwent preoperative assessment including magnetic resonance imaging (MRI) and subsequent surgery including systematic lymphadenectomy. The volume index, which we previously reported in the literature, was defined as the product of maximum longitudinal diameter along the uterine axis, maximum anteroposterior diameter in a sagittal section image, and maximum horizontal diameter in a horizontal section image according to MRI data, from 425 Japanese women with endometrial cancer. Relationships between lymph node metastasis and results of preoperative examinations including volume index were analyzed by logistic regression analysis., Results: The prevalence of affected lymph nodes was 14.2%. Multivariate analysis showed that high-grade histology assessed by endometrial biopsy [odds ratio (OR); 2.9, 95% confidence interval (CI): 1.4-6.4], volume index (OR; 2.4, 95% CI: 1.1-5.3), node enlargement assessed by MRI (OR; 4.2, 95% CI: 1.4-13.2), and high serum cancer antigen (CA)125 level (OR; 3.6, 95% CI: 1.6-8.1) were significantly and independently related to lymph node metastasis. When volume index was excluded from the analysis, myoinvasion assessed by MRI was an independent risk factor for lymph node metastasis as well as high-grade histology, node enlargement, and high serum CA125 level., Conclusion: Volume index is compatible with myometrial invasion as a factor for predicting lymph node metastasis in endometrial cancer., (© 2013.)

Objective: Tumor metabolic activity is a significant prognostic factor for endometrial cancer; however, there are few reports on the clinical importance of metabolic tumor volume (MTV) in patients with endometrial cancer. Therefore, we evaluated the prognostic value of preoperative MTV measured by (18)F-FDG PET/CT and MRI in a group of these patients., Methods: We retrospectively reviewed patients with pathologically proven endometrial cancer who had undergone preoperative (18)F-FDG PET/CT and MRI scans. The prognostic significance of PET/CT parameters and other clinicopathological variables was evaluated., Results: A total of 76 consecutive patients were included in the study. The median follow-up duration was 27 mo (range 3 to 96 mo) after surgery. MTV was correlated with FIGO stage and SUVmax. Age and FIGO stage were independent prognostic factors for recurrence in the multivariate analysis. In the subgroup analysis for 62 patients with endometrioid endometrial cancer, age (hazard ratio 1.098, P = 0.007, 95% confidence interval (CI) 1.026-1.175) and an MTV index of ≥ 876.4 (hazard ratio 5.795, P = 0.032, 95% CI 1.160-28.958) were determined to be independent prognostic factors of recurrence, and there was a statistically significant difference in progression-free survival (PFS) between patients in the high MTV and low MTV groups (log-rank test, P = 0.002)., Conclusion: Preoperative MTV of the primary tumor was an independent prognostic factor for PFS and was significantly associated with recurrence in patients with endometrioid endometrial cancer. MTV is a promising tool for the prediction of outcome in patients with endometrioid endometrial cancer., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To estimate the oncologic and pregnancy outcomes after oral progestin treatment of women of reproductive age with stage IA endometrial adenocarcinoma with stage IA, grade 1 differentiation with superficial myometrial invasion or stage IA, grade 2-3 differentiation with or without superficial myometrial invasion., Methods: Medical records of 48 women (age 40 years or younger) with endometrioid adenocarcinoma of the uterus who met inclusion criteria and were treated conservatively with oral progestin were reviewed. Follow-up was performed primarily with imaging techniques followed by endometrial biopsy when indicated., Results: The median age was 30 years (range, 23-40 years). Fourteen patients (29.2%) received daily oral megestrol acetate (median dose 160 mg per day, range 40-240 mg per day) and 34 (70.8%) received daily oral medroxyprogesterone acetate (median dose 500 mg per day, range 80-1,000 mg per day). Complete responses were observed for 37 patients (77.1%) after the median treatment duration of 10 months (range 3-20 months). Complete response rates were 76.5%, 73.9%, and 87.5% for patients with stage IA, grade 2-3 without myometrial invasion (n=17), for patients with stage IA, grade 1 with superficial myometrial invasion (n=23), and for patients with stage IA, grade 2-3 with superficial myometrial invasion (n=8), respectively (P=.731). Recurrence rates for 37 patients who achieved complete response after a median follow-up time of 48 months (range 7-136 months) were 23.1%, 47.1%, and 71.4%, respectively (P=.104). None experienced disease progression or died of the disease. Nine patients gave birth to 10 healthy newborns., Conclusion: Progestin treatment appears to be reasonably effective for patients with stage IA, grade 2-3 differentiation without myometrial invasion and patients with stage IA grade 1 differentiation with superficial myometrial invasion., Level of Evidence: III.

Objective: The Korean Gynecologic Oncology Group (KGOG) recently proposed new pre-operative criteria to identify a low-risk group for lymph node metastasis in endometrial cancer. The aim of this study was to test whether the good performance of the criteria can be reproducible in diverse clinical settings., Methods: From two Japanese hospitals, 319 patients with endometrial cancer who underwent systemic lymphadenectomy were retrospectively reviewed. In one hospital, para-aortic lymphadenectomy was routinely performed, but it was selectively performed in the other hospital. The performance of the criteria was determined by adjusting the false-negative rate (FNR) at the given prevalence of nodal metastasis of 10% using Bayes' theorem., Results: Nodal metastasis rate of the study population was 12.9%. The KGOG low-risk criteria identified 181 of 319 patients as a low-risk group (51%), and three false-negative cases were found (1.9%). Despite a significant difference in the nodal metastasis rate (18.2% and 8.8%, P=.012) and the surgical policy for para-aortic lymphadenectomy (100% and 48.9%, P<.001) between the two hospitals, KGOG criteria consistently showed a very low adjusted FNR at the prevalence of 10% in both hospitals (1.8% vs. 1.1%, respectively). Among the entire study population, the adjusted FNR was 1.4% (95% confidence interval, .5% to 4.3%), which was similar to the FNR of 1.3% in our previous study., Conclusion: The KGOG low-risk criteria accurately identified a low-risk group for lymph node metastasis with acceptable false negativity regardless of diverse clinical settings., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To analyze the outcomes of second round of fertility-sparing management using progestin in patients with recurrent endometrial cancer after successful fertility-sparing management using progestin., Methods: We reviewed 45 patients who had recurrence after achieving complete remission by fertility-sparing management using progestin for presumed stage IA, grade 1, endometrioid adenocarcinoma of the uterus. Of 45 patients, 33 tried progestin re-treatment at recurrence and were included in this study., Results: Recurrent disease was atypical hyperplasia in 13 patients (39%) and grade 1 endometrioid adenocarcinoma in 20 patients (61%) which were confined to the endometrium. Thirty patients (91%) received medroxyprogesterone acetate (dose range, 80-500 mg/day) and three patients (9%) received megestrol acetate (dose range, 80-160 mg/day), with 29 patients receiving a dose of 500 mg/day of medroxyprogesterone acetate. The median duration of treatment was 6 months (range, 3-19 months). Five patients failed to respond to progestin re-treatment and underwent definitive surgical treatment including hysterectomy. Twenty eight patients (85%) showed complete response to progestin re-treatment. The median follow-up time after progestin re-treatment in 28 patients who achieved complete remission was 51 months (range, 24-160 months). During follow-up, five patients had second recurrence after median time interval of 14 months (range, 4-82 months). All patients who tried progestin re-treatment are alive without evidence of disease., Conclusion: Progestin re-treatment in patients with recurrent endometrial cancer was effective and safe. Therefore, this can be recommended for young women who still want to preserve fertility at recurrence after complete response to progestin., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To analyse the long-term oncologic outcomes of a fertility-sparing management using oral progestin in young women with endometrial cancer., Methods: We analysed 148 patients (age≤40 years) with stage IA, grade 1, endometrioid adenocarcinoma of the uterus who underwent fertility-sparing management using daily oral medroxyprogesterone acetate (MPA) or megestrol acetate (MA)., Results: 115 (77.7%) showed complete response (CR) to progestin treatment, and 35 (30.4%) of them experienced recurrence after median follow-up time of 66 months. The 5-year recurrence-free survival was 68% (95% confidence interval [CI], 58.5-76.9%). However, 33 patients (22.3%) who failed to achieve CR underwent definitive surgical management, and no one had recurrence after median follow-up time of 41 months. During progestin treatment and at the time of recurrence, no patient showed clinical progression of disease over stage IA. Body mass index (BMI) ≥25 kg/m(2) was the only significant factor associated with a failure to achieve CR (odds ratio [OR], 3.00; 95% CI, 1.35-6.66; P=0.007). Upon multivariate analysis, BMI≥25 kg/m(2) (OR, 2.14; 95% CI, 1.06-4.31; P=0.033) was significantly associated with a higher risk of recurrence and the use of MPA (compared to MA) (OR, 0.44; 95% CI, 0.22-0.88; P=0.021), maintenance treatment (OR, 0.22; 95% CI, 0.05-0.94; P=0.042) and pregnancy (OR, 0.25; 95% CI, 0.11-0.56; P=0.001) were significantly associated with a lower risk of recurrence., Conclusion: Fertility-sparing management was highly effective and safe. BMI<25 kg/m(2), MPA (compared to MA), maintenance treatment and pregnancy were associated with higher possibility of long-term success., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: To analyze pregnancy outcomes in young women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus after successful fertility-sparing management using progestin., Methods: We reviewed the medical records of 141 women with stage IA, grade 1 endometrioid adenocarcinoma of the uterus who had complete remission after progestin treatment. Statistical analysis was performed using Student's t test or Mann-Whitney U test for continuous variables, using χ or Fisher's exact test for categorical variables, and using log-rank test for survival comparison., Results: Fifty-four (38.3%) women in the study cohort had a history of infertility. Seventy (49.6%) of the 141 patients tried to conceive with 44 (62.9%) receiving fertility drugs. The median interval to attempted pregnancy after treatment was 5 months (range 1-31 months). The median age at the time of the pregnancy trial was 32.4 years (range 23-40 years). Fifty-one (73%) of 70 women who tried to conceive were successful and 46 (66%) gave birth to 58 live neonates. The spontaneous abortion rate, ectopic pregnancy rate, and preterm delivery rates in our cohort were 24%, 2.8%, and 11.5%, respectively. The 5-year disease-free survival was similar between patients who received fertility drugs (n=44) or who did not (n=97) (73% compared with 62%, P=.335), and this rate was significantly higher in patients who achieved at least one pregnancy (n=51) than those who did not (n=90) (76% compared with 62%, P=.028)., Conclusions: Although the proportion of patients with a history of subfertility or infertility was high in our cohort, the pregnancy outcomes were very promising using assisted reproductive technology. The use of fertility drugs was not associated with a higher incidence of cancer recurrence after successful fertility-sparing management in this study population., Level of Evidence: II.

A prospective multicenter trial has been started in Korea to investigate the treatment efficacy of a levonorgestrel-releasing intrauterine system plus medroxyprogesterone acetate in young women with early-stage endometrial cancer. A number of studies have reported the effectiveness of hormonal therapy using systemic progestin in women clinically diagnosed with early endometrial adenocarcinoma at Stage IA, Grade 1, who want to maintain reproductive potential. In addition, several recent studies reported the use of a levonorgestrel-releasing intrauterine system to treat patients at a high risk of perioperative complications who cannot tolerate systemic progesterone because of its adverse effects. However, there has been no prospective multicenter trial that investigated the effectiveness of treatment with systemic progesterone in combination with intrauterine progesterone in young women with endometrial cancer. Young patients with histologically confirmed Grade 1 endometrioid adenocarcinoma that is presumably confined to the endometrium, who desired to preserve their fertility potential, undergo levonorgestrel-releasing intrauterine system insertion and are administered medroxyprogesterone acetate at a dosage of 500 mg/day concurrently. The follow-up and treatment response assessment were implemented at a 3-month interval with office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in place, and dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system. The primary endpoint is the complete response rate. The secondary endpoint is to estimate the consistency of the results of the office endometrial aspiration biopsy with the levonorgestrel-releasing intrauterine system in the uterus and a dilatation and curettage after removal of the levonorgestrel-releasing intrauterine system.

Purpose: Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are measures of metabolic activity of tumors determined by fluorine-18 fluorodeoxyglucose ([(18)F]FDG) uptake on PET/CT images. The purpose of this study was to investigate the relationship between functional tumor parameters (MTV and TLG) and clinical outcomes in patients with epithelial ovarian cancer (EOC)., Methods: Fifty-five patients with EOC who had undergone [(18)F]FDG PET/CT before surgical staging were included in this retrospectively study. For each patient, we determined the highest (SUV(max) and SUV(avg)), the cumulative TLG, and the sum of all MTV, and compared their predictive value of recurrence and the effects of pretreatment functional tumor activity on progression-free interval (PFI)., Results: The median duration of PFI was 11 (range 3-43) months, and 20 patients (36.4%) experienced recurrence. Poor outcome was associated with higher values for both the MTV (P = 0.022, hazard ratio 5.571, 95% confidence interval 1.279-24.272) and the TLG (P = 0.037, hazard ratio 2.967, 95% confidence interval 1.065-8.265). The Kaplan-Meier survival graphs showed a significant difference in PFI between the groups categorized by MTV and TLG, respectively (P = 0.01 for MTV, P = 0.0287 for TLG, log rank test)., Conclusions: Pretreatment metabolic parameters such as MTV and TLG showed statistically significant association with recurrence in patients with EOC. These values can be useful quantitative criteria for disease prognostication in patients with EOC before treatment.

Objectives: To evaluate the correlation of pre-operative systemic inflammatory response (SIR) markers with lymph node (LN) metastasis compared with serum CA-125 in endometrioid endometrial adenocarcinoma., Study Design: Retrospective review of 319 patients who were pathologically proven to have endometrioid endometrial adenocarcinoma after staging operations. Serum CA-125 and pre-operative SIR markers [neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), C-reactive protein (CRP), albumin, platelets and fibrinogen] were assessed. Receiver operating characteristic (ROC) curves were plotted for each SIR marker and serum CA-125., Results: NLR, PLR and serum CA-125 were higher in the LN-positive group compared with the LN-negative group (p=0.003, 0.012 and 0.025, respectively). Serum albumin was significantly lower in the LN-positive group compared with the LN-negative group (p<0.001). ROC curves demonstrated the best cut-off values for NLR (≥1.97), PLR (≥9.14), albumin (≤4.15 g/dl) and serum CA-125 (≥32.50 U/ml) for pre-operative diagnosis of LN metastasis. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of serum CA-125 were 63.3%, 87.6%, 37.3%, 95.4% and 85.1%, respectively. No pre-operative SIR markers were superior to serum CA-125 in terms of sensitivity, specificity, PPV, NPV or accuracy, with the exception of the slightly higher sensitivity of PLR (64.5%)., Conclusions: Pre-operative SIR markers do not appear to be more effective in predicting LN metastasis than serum CA-125 in endometrioid endometrial adenocarcinoma., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The aim of this study was to develop a preoperative risk prediction model for lymph node metastasis in patients with endometrial cancer and to identify a low-risk group before surgery., Patients and Methods: The medical records of 360 patients with endometrial cancer who underwent surgical staging were collected from four institutions and were retrospectively reviewed. By using serum CA-125 levels, preoperative biopsy data, and magnetic resonance imaging (MRI) data, a multivariate logistic model was created. Patients whose predicted probability was less than 4% were defined as low risk. The developed model was externally validated in 180 patients from two independent institutions., Results: Serum CA-125 levels and three MRI parameters (deep myometrial invasion, lymph node enlargement, and extension beyond uterine corpus) were found to be independent risk factors for nodal metastasis. The model classified 53% of patients as part of a low-risk group, and the false negative rate was 1.7%. In the validation cohort, the model classified 43% of patients as low-risk, and the false negative rate was 1.4%. The model showed good discrimination (area under the receiver operator characteristic curve = 0.85) and was calibrated well. The negative likelihood ratio of our low-risk criteria was 0.11 (95% CI, 0.04 to 0.29), which was equivalent to the false-negative rate of 1.3% (95% CI, 0.5% to 3.3%) at the assumed prevalence of nodal metastasis of 10%., Conclusion: Using serum CA-125 and MRI as criteria resulted in the accurate identification of a low-risk group for lymph node metastasis among patients with endometrial cancer.

Purpose: The objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy., Methods: The authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy., Results: Among 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (p = 0.02) and lymphvascular space invasion (p = 0.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5-120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (p = 0.77), even in high-risk patients (p = 0.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR) = 7.38; 95% confidence interval (CI) = 1.86-29.23; p = 0.004)., Conclusions: Although a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.

Objective: To assess the feasibility of using medroxyprogesterone acetate (MPA) and levonorgestrel intrauterine system (LNG-IUS) to treat early-stage endometrial cancer in young women who want to preserve their reproductive potential., Methods: Prospective observational study of 5 young patients (mean [SD] age, 38.4 [4.8] years; range, 33-41 years) with a grade 1 endometrial cancer that is presumably confined to the endometrium. The subjects were given a daily oral dose of 500 mg of MPA and LNG-IUS placement. They were followed with dilation and curettage every 3 months., Results: Complete remission was shown in 4 of 5 patients, and one patient showed partial remission. Biopsy results were negative in 2 patients at 3 months, in 1 patient at 6 months, and in 1 patient at 12 months. No treatment-related complications occurred. No recurrence was found during the follow-up period (mean [SD], 10.2 [3.6] months; range, 6-16 months)., Conclusions: The concomitant use of MPA with LNG-IUS is feasible for conservative treatment of early-stage endometrial cancer in young women who want to preserve their reproductive potential.

Purpose: The purpose of this study was to determine whether post-treatment [(18)F]fluorodeoxyglucose (FDG) uptake measured as the maximum standardized uptake value (SUV(max)) by integrated positron emission tomography (PET)/computed tomography (CT) imaging has prognostic significance in patients with endometrial carcinoma., Methods: Patients previously treated by primary surgical staging for endometrial carcinoma were imaged with integrated FDG PET/CT during surveillance. PET/CT findings were compared with histological or clinical evaluation, and the relationship between SUV(max) on PET/CT and recurrence was examined., Results: A total of 61 patients were eligible for analysis. Medical records were retrospectively reviewed for clinical data, treatment modalities and outcome. The median duration of follow-up was 31 months (range 6-102 months) post-treatment. SUV(max) levels were inversely associated with disease-free survival (DFS). Patients were divided into two groups according to SUV(max) (< 4.25 versus ≥ 4.25). The Kaplan-Meier survival graph showed a significant difference in DFS between groups [p < 0.001, hazard ratio (HR) 12.959, 95% confidence interval (CI) 3.650-46.011]. In multivariate analyses, post-treatment SUV(max) (uncategorized values) evaluated by surveillance PET/CT (p = 0.001, HR 1.199, 95% CI 1.077-1.334) and serous adenocarcinoma histology (p = 0.028, HR 5.594, 95% CI 1.207-25.931) were significantly associated with recurrence., Conclusion: Post-treatment FDG uptake as measured by SUV(max) showed a significant association with recurrence in patients with endometrial carcinoma and may be used as a new useful prognostic marker.

Objective: To evaluate the role of serum CA-125 levels for preoperative counseling in endometrioid endometrial cancer (EEC)., Methods: We reviewed 413 patients with EEC from 6 tertiary medical centers between July 1996 and June 2008. All patients were divided into (1) 4 categories of preoperative serum CA-125 levels: <18 U/mL (n=203); 18-35 U/mL (n=114); 36-70 U/mL (n=53); >70 U/mL (n=43) or (2) 3 categories: low-risk (n=240); intermediate-risk (n=99); high-risk diseases (n=74)., Results: Receiver operative curves showed the best cut-off values of 16.2-40.8 U/mL for predicting prognostic factors with 53.4-84.2% of sensitivity, 43.9-81.7% of specificity, 48.8-82.1% of positive predictive value (PPV), 48.5-83.8% of negative predictive value (NPV) and 48.6-83.0% of accuracy. Especially, adnexal involvement was predicted with the highest accuracy (83.0%) at >or=40.8 U/mL. The best cut-off values for preoperative selection of intermediate- to high-risk, and high-risk diseases were 17.3 U/mL and 21.9 U/mL (62.4% and 68.9% of sensitivity; 54.6% and 64.3% of specificity; 57.9% and 64.2% of PPV; 59.2% and 67.4% of NPV, 58.5% and 65.8% of accuracy). Furthermore, >70 U/mL of preoperative serum CA-125 levels was a prognostic factor for poor progression-free and overall survivals., Conclusions: Serum CA-125 levels may not be useful for predicting most of prognostic factors, and may not contribute to preoperative selection of patients with intermediate- or high-risk disease who need adjuvant radiotherapy in EEC. However, serum CA-125 levels may be helpful in preoperative counseling for young patients who want ovarian preservation, and >70 U/mL could be considered as a risk factor for poor survival., (Copyright 2010 Elsevier Inc. All rights reserved.)

Objective: We aimed to evaluate the role of body mass index (BMI) as a risk and prognostic factor of endometrioid uterine cancer in Korean women., Methods: The records of 937 patients with endometrioid uterine cancer treated between 2000 and 2006 in Korea were reviewed. To determine the disease risk by BMI, four age-matched controls were recruited from healthy women (1-year age group)., Results: The obese (BMI > or =25 kg/m(2)) and overweight (23 kg/m(2)< or = BMI <25 kg/m(2)) women had an increased risk for endometrioid uterine cancer (OR=3.161, 95% CI=2.655-3.763 and OR=1.536, 95% CI=1.260-1.873, respectively) compared to the non-obese (BMI <23 kg/m(2)) women. That is, an increment of 1 kg/m(2) caused an 18% increase in the endometrioid uterine cancer risk (OR=1.181, 95% CI=1.155-1.207). However, there was no difference in overall survival according to the BMI-based subgroups (log-rank=0.366, p=0.8328). The crude Cox model showed that obesity was not associated with the patients' overall survival when the obese and non-obese women were compared (crude HR=0.82, 95% CI=0.40-1.66). Furthermore, there was a significant trend toward a better prognosis at increased increments of BMI (p for trend<0.001), but this was not found in the multivariate analysis., Conclusions: A high BMI was a significant risk factor for endometrioid uterine cancer in an Asian population. However, it was not associated with overall survival, in spite of the earlier tumor stage of the obese women., (Copyright 2010 Elsevier Inc. All rights reserved.)

Aim: We sought to compare survival and toxicity between paclitaxel/carboplatin (TC) and doxorubicin/cisplatin (AP) for concurrent chemoradiation (CCR) in intermediate- or high-risk endometrioid endometrial cancer., Methods: The clinical data of 40 patients with intermediate- (FIGO stage IC-IIB, n = 12) or high-risk endometrioid endometrial cancer (FIGO stage IIIA-IVA, n = 28) were reviewed retrospectively between March 2000 and December 2007, who were treated with TC (n = 23, group 1) or AP (n = 17, group 2) for CCR after surgery., Results: Progression-free survival (PFS) and overall survival (OS) were not different between groups 1 and 2 (median PFS and OS; 35 vs 24 and 76 vs 39 months, respectively, P > 0.05). However, >or=6 cycles of chemotherapy improved PFS compared with 3-5 cycles of chemotherapy (51 vs 21 months, P = 0.04), suggesting that >or=6 cycles of chemotherapy was an independent prognostic factor improving PFS (adjusted HR, 0.27; 95% CI, 0.08 to 0.91; P = 0.04). Grade 3 or 4 hematological and non-hematological, especially, gastrointestinal, toxicities related with chemotherapy during CCR were more common in group 2 than in group 1, whereas there was no difference in grade 3 or 4 late complication by CCR between the 2 groups., Conclusion: These findings suggest that TC may have comparable efficacy to AP for CCR with lesser toxicity, and >or=6 cycles of chemotherapy may be more beneficial than 3-5 cycles of chemotherapy in intermediate- or high-risk endometrioid endometrial cancer. However, large-scale randomized controlled trials are needed to support these results.

To determine whether radical hysterectomy is necessary in the treatment of endometrial cancer patients with cervical involvement, we reviewed the medical records of women who underwent primary surgical treatment for endometrial carcinoma and selected patients with pathologically proven cervical invasion. Among 133 patients, 62 patients underwent extrafascial hysterectomy (EH) and 71 radical or modified radical hysterectomy (RH). The decision regarding EH or RH was made at the discretion of the attending surgeon. The sensitivity of pre-operative magnetic resonance imaging for cervical invasion was 44.7% (38/85). In RH patients, 10/71 (14.1%) patients had frankly histologic parametrial involvement (PMI). All were stage III or over. Eight of 10 patients had pelvic/paraaortic node metastasis and two showed extrauterine spread. In 74 patients with stage II cancer, RH was performed in 41 and PMI was not seen. Sixty-six (89.2%) patients had adjuvant radiation therapy and there were 3 patients who had developed recurrent disease in the RH group and none in the EH group (Mean follow-up: 51 months). Although these findings cannot conclusively refute or support the necessity of radical hysterectomy in patients with cervical extension, it is noteworthy that the risk of PMI seems to be minimal in patients with a tumor confined to the uterus without evidence of extrauterine spread.

Objective: To evaluate whether we could accurately predict lymph node (LN) metastasis with preoperative tests in endometrial cancer. Design. Retrospective study., Setting: Seoul National University Hospital, South Korea. Population. Three hundred patients with endometrial cancer who underwent surgical staging including lymphadenectomy between January 1999 and July 2007., Methods: We reviewed the medical records of 300 patients with endometrial cancer. The preoperative factors used to predict LN metastasis were as follows: old age (> or = 55 years), serum CA-125 level [level > or = 20 U/mL (if age < 50 years), level > or = 28 U/mL (if age > or = 50 years)], non-endometrioid histologic type and Grade 3, metastatic LN assessed by pelvic MRI or CT, and deep myometrial invasion assessed by pelvic MRI only. Logistic regression analysis was used to determine the significant predictive factors., Main Outcome Measures: Sensitivity/specificity and false positive/negative rates., Results: Thirty patients had LN metastasis. Although LN evaluation by pelvic MRI or CT and high CA-125 level were the significant independent predictors for LN metastasis, the sensitivity/specificity and false positive/negative rates for LN metastasis by these two combined preoperative tests were 86.7%/71.4% and 68.7%/2.7%, respectively. However, the sensitivity/specificity and false positive/negative rates for LN metastasis by six combined preoperative tests were 100%/28.9% and 84.6%/0%, respectively., Conclusions: The six combined preoperative tests are useful in selecting patients without LN metastasis in endometrial cancer. Lymphadenectomy could be avoided in about 29% of patients with endometrial cancer who have no LN metastasis by using six combined preoperative tests.