{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:19:58Z","timestamp":1787721598603,"version":"build-2784847793"},"reference-count":51,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>This review examines the clinical and practical implications of embedding molecular profiles directly into the 2023 FIGO staging system for endometrial carcinoma, in the context of the 2025 ESGO\/ESTRO\/ESP guidelines. The primary purpose is to navigate a central conflict in modern oncology: how to deliver increasingly personalized care while maintaining a globally accessible, equitable, and standardized cancer classification system. The 2023 FIGO update represents a paradigm shift from the traditional dualistic model (Type I versus Type II) by allowing molecular findings to redefine stage itself. While this integration offers clear benefits, it introduces significant challenges. First, the system depends on advanced molecular testing, creating a \u201crich-poor\u201d divide where patients in resource-limited settings are systematically overtreated because testing is unavailable. Second, stage becomes unstable, changing with sequential histologic and molecular re-review, which causes confusion for patients and clinicians. Third, the system lumps prognostically distinct histotypes (Serous, Clear Cell, Carcinosarcoma, and Grade 3 Endometrioid) into a single aggressive stage, obscuring meaningful differences in survival. Fourth, it relies on subjective parameters such as \u201csubstantial\u201d lymphovascular space invasion, for which no standardized definition exists, leading to high inter-observer variability. After analyzing these controversies, the review proposes a pragmatic solution: decouple anatomical staging from molecular risk stratification. Staging should remain a purely anatomical, universally applicable descriptor of tumor extent, while molecular and histologic data are used separately within a dynamic risk assessment model, as suggested by the European guidelines. This dual-track approach preserves global comparability, reduces inequity, and maintains diagnostic stability, while still enabling personalized treatment where advanced diagnostics are available.<\/jats:p>","DOI":"10.3390\/cancers18172748","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:20:28Z","timestamp":1787592028000},"page":"2748","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Implications of Incorporating Molecular Profiles into the Staging of Endometrial Cancer: A Critical Review of the 2023 FIGO System on the Wave of 2025 ESGO\/ESTRO\/ESP Guidelines"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6964-5152","authenticated-orcid":false,"given":"Angela","family":"Santoro","sequence":"first","affiliation":[{"name":"Pathology Unit, Department of Laboratory and Hematology Sciences Fondazione Policlinico Universitario, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Pathology Institute, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4808-2052","authenticated-orcid":false,"given":"Giuseppe","family":"Angelico","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4810-1201","authenticated-orcid":false,"given":"Antonio","family":"d\u2019Amati","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratory and Hematology Sciences Fondazione Policlinico Universitario, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Maccio","sequence":"additional","affiliation":[{"name":"Anatomic Pathology, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Bragantini","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ospedale San Maurizio, 39100 Bolzano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Fanfani","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Fagotti","sequence":"additional","affiliation":[{"name":"Gynecologic Oncology Unit, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy"},{"name":"Catholic University of the Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4473-7560","authenticated-orcid":false,"given":"Gian Franco","family":"Zannoni","sequence":"additional","affiliation":[{"name":"Pathology Unit, Department of Laboratory and Hematology Sciences Fondazione Policlinico Universitario, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Pathology Institute, Catholic University of Sacred Heart, 00168 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/0090-8258(83)90111-7","article-title":"Two pathogenetic types of endometrial carcinoma","volume":"15","author":"Bokhman","year":"1983","journal-title":"Gynecol. Oncol."},{"key":"ref_2","first-page":"63","article-title":"An update of the classical Bokhman\u2019s dualistic model of endometrial cancer","volume":"15","author":"Danielska","year":"2016","journal-title":"Prz. Menopauzalny"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/nature12113","article-title":"The Cancer Genome Atlas Research Network. 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