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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
by
, , ,
Angela Santoro
1,2
,
Giuseppe Angelico
3
,
Antonio d’Amati
1
,
Livia Maccio
4, 
Emma Bragantini
5,
Francesco Fanfani
6,7,
Anna Fagotti
6,7 and
Gian Franco Zannoni
1,2,* 1
Pathology Unit, Department of Laboratory and Hematology Sciences Fondazione Policlinico Universitario, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy
2
Pathology Institute, Catholic University of Sacred Heart, 00168 Rome, Italy
3
Department of Medicine and Surgery, Kore University of Enna, 94100 Enna, Italy
4
Anatomic Pathology, Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy
5
Department of Pathology, Ospedale San Maurizio, 39100 Bolzano, Italy
6
Gynecologic Oncology Unit, Department of Women, Children and Public Health Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
7
Catholic University of the Sacred Heart, 00168 Rome, Italy
*
Author to whom correspondence should be addressed.
Cancers 2026, 18(17), 2748; https://doi.org/10.3390/cancers18172748
Submission received: 13 July 2026
/
Revised: 13 August 2026
/
Accepted: 24 August 2026
/
Published: 24 August 2026
(This article belongs to the Special Issue Gynecological Cancers: Molecular Insights to Precision Therapy)
Simple Summary
The present paper reviews the 2023 FIGO staging system for endometrial cancer, which for the first time incorporates molecular testing (like POLE mutations and p53 status) alongside traditional anatomical findings. This update reflects tumor biology and helps avoid over- or under-treating patients, though it also introduces some practical challenges. Access to molecular testing varies widely, so a patient’s cancer stage can depend partly on where they are treated, not just their tumor’s biology. Staging can also change after surgery once molecular results come back, which requires clear communication with patients. The paper also discusses inconsistent grouping of aggressive cancer subtypes and variability in measuring lymphovascular invasion as areas needing further standardization. We therefore propose that anatomical stage remain fixed and universal, while molecular and pathological findings guide a separate risk-stratification system for treatment planning, keeping staging simple and consistent worldwide while still enabling personalized care.
Abstract
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.
