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Background: Quality of surgical care as a crucial component of a comprehensive multi-disciplinary management improves outcomes in patients with endometrial carcinoma, notably helping to avoid suboptimal surgical treatment. Quality indicators (QIs) enable healthcare professionals to measure their clinical management with regard to ideal standards of care., Objective: In order to complete its set of QIs for the surgical management of gynecological cancers, the European Society of Gynaecological Oncology (ESGO) initiated the development of QIs for the surgical treatment of endometrial carcinoma., Methods: QIs were based on scientific evidence and/or expert consensus. The development process included a systematic literature search for the identification of potential QIs and documentation of the scientific evidence, two consensus meetings of a group of international experts, an internal validation process, and external review by a large international panel of clinicians and patient representatives. QIs were defined using a structured format comprising metrics specifications, and targets. A scoring system was then developed to ensure applicability and feasibility of a future ESGO accreditation process based on these QIs for endometrial carcinoma surgery and support any institutional or governmental quality assurance programs., Results: Twenty-nine structural, process and outcome indicators were defined. QIs 1-5 are general indicators related to center case load, training, experience of the surgeon, structured multi-disciplinarity of the team and active participation in clinical research. QIs 6 and 7 are related to the adequate pre-operative investigations. QIs 8-22 are related to peri-operative standards of care. QI 23 is related to molecular markers for endometrial carcinoma diagnosis and as determinants for treatment decisions. QI 24 addresses the compliance of management of patients after primary surgical treatment with the standards of care. QIs 25-29 highlight the need for a systematic assessment of surgical morbidity and oncologic outcome as well as standardized and comprehensive documentation of surgical and pathological elements. Each QI was associated with a score. An assessment form including a scoring system was built as basis for ESGO accreditation of centers for endometrial cancer surgery., Competing Interests: Competing interests: NC: advisory boards for Akesobio, Ensai, GSK, AstraZeneca, Mersana, Seattle Genetics, eTherRNA immunotherapies; NV grants for travelling from Roche, Genmab, Amgen and educational fees from MSD, Medscape Oncology, TouchIME. NRA-R: research grants (paid to his institution) from Stryker/Novadaq and GRAIL and funds from the NIH/NCI Cancer Center (support grant P30 CA008748). BA: advisory boards for Roche, Tesaro/GSK, Amgen, MSD; grants for traveling from Roche, Tesaro/GSK, Pharmamar; and educational fees from Roche, Tesaro/GSK, Celgene, Clovis, AstraZeneca, Novartis. DC: advisory boards for Akesobio, AstraZeneca, GSK, MSD, Novocure, Roche, Seagen, Sotio. AF: advisory boards for AstraZeneca, MSD and grants for traveling from Pharmamar. CF: advisory boards for Roche, Ethicon, Sequana, GSK, MSD/AZ, Clovis, Tesaro. CM: advisory boards for Roche, Novartis, Amgen, MSD, AstraZeneca, Pfizer, Pharmamar, Cerulean, Vertex, Tesaro, GSK and grants for traveling from Roche, Novartis, Amgen, MSD, Pharmamar, AstraZeneca, Tesaro, GSK. DQ: advisory boards for Arquer Diagnostics Ltd. JS: advisory boards for Novocure, Roche, Pfizer, AstraZeneca, GSK, Clovis, Eisei and grants for traveling from Roche, GSK, AstraZeneca. IV: consulting activities for Agenus, Aksebio, Amgen (Europe) GmbH, AstraZeneca, Bristol Myers Squibb, Clovis Oncology Inc, Carrick Therapeutics, Deciphera Pharmaceuticals, Eisai, Elevar Therapeutics, F. Hoffman-La Roche Ltd, Genmab, GSK, Immunogen Inc, Jazzpharma, Karyopharm, Mersana, Millenium Pharmaceuticals, MSD, Novocure, Novartis, Octimet Oncology, NV, Oncoinvent AS, Seagen, Sotio a.s., Verastem Oncology, Zentalis; contracted research (via KULeuven) for Oncoinvent AS, Genmab; corporate sponsored research for Amgen, Roche; and grants for traveling and accommodations from Amgen, MSD, Tesaro, AstraZeneca, Roche. PW: advisory boards for Amgen, AstraZeneca, MSD, Novartis, Pfizer, Roche, Clovis, GSK and grants for traveling from Roche, Novartis, AstraZeneca. JP: advisory boards for Intuitive surgical, Medtronics., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Our aim was to investigate whether molecular classification can be used to refine prognosis in grade 3 endometrial endometrioid carcinomas (EECs). Grade 3 EECs were classified into 4 subgroups: p53 abnormal, based on mutant-like immunostaining (p53abn); MMR deficient, based on loss of mismatch repair protein expression (MMRd); presence of POLE exonuclease domain hotspot mutation (POLE); no specific molecular profile (NSMP), in which none of these aberrations were present. Overall survival (OS) and recurrence-free survival (RFS) rates were compared using the Kaplan-Meier method (Log-rank test) and univariable and multivariable Cox proportional hazard models. In total, 381 patients were included. The median age was 66 years (range, 33 to 96 y). Federation Internationale de Gynecologie et d'Obstetrique stages (2009) were as follows: IA, 171 (44.9%); IB, 120 (31.5%); II, 24 (6.3%); III, 50 (13.1%); IV, 11 (2.9%). There were 49 (12.9%) POLE, 79 (20.7%) p53abn, 115 (30.2%) NSMP, and 138 (36.2%) MMRd tumors. Median follow-up of patients was 6.1 years (range, 0.2 to 17.0 y). Compared to patients with NSMP, patients with POLE mutant grade 3 EEC (OS: hazard ratio [HR], 0.36 [95% confidence interval, 0.18-0.70]; P=0.003; RFS: HR, 0.17 [0.05-0.54]; P=0.003) had a significantly better prognosis; patients with p53abn tumors had a significantly worse RFS (HR, 1.73 [1.09-2.74]; P=0.021); patients with MMRd tumors showed a trend toward better RFS. Estimated 5-year OS rates were as follows: POLE 89%, MMRd 75%, NSMP 69%, p53abn 55% (Log rank P=0.001). Five-year RFS rates were as follows: POLE 96%, MMRd 77%, NSMP 64%, p53abn 47% (P=0.000001), respectively. In a multivariable Cox model that included age and Federation Internationale de Gynecologie et d'Obstetrique stage, POLE and MMRd status remained independent prognostic factors for better RFS; p53 status was an independent prognostic factor for worse RFS. Molecular classification of grade 3 EECs reveals that these tumors are a mixture of molecular subtypes of endometrial carcinoma, rather than a homogeneous group. The addition of molecular markers identifies prognostic subgroups, with potential therapeutic implications.