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

Vollständiger Abstract

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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 “rich-poor” 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 “substantial” 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.