No prognostic role for FIGO grading in mismatch repair deficient endometrial carcinoma
- Author(s)
- Wakkerman, FC; Post, CCB; Ørtoft, G; Høgdall, E; Jobsen, JJ; Razack, R; de Kroon, CD; Nout, RA; Tseng, DSJ; Kuijsters, N; Haverkort, MAD; Powell, ME; Leary, A; Mileshkin, LR; Khaw, P; Shepherd, LE; de Boer, SM; Kroep, JR; Smit, VTHBM; Creutzberg, CL; Horeweg, N; Bosse, T;
- Journal Title
- European Journal of Cancer
- Publication Type
- Research article
- Abstract
- INTRODUCTION: The prognostic value of FIGO grading in endometrial cancer (EC) varies across molecular subgroups: it is no longer considered relevant in POLEmut and p53abn tumours, but remains prognostic in NSMP tumours. Its relevance is unclear in mismatch repair deficient (MMRd) EC. Using a large collection of molecularly classified EC, this study evaluated the prognostic role of FIGO grading in MMRd EC. METHODS: Data from three randomised trials (PORTEC-1 ( = 714); PORTEC-2 (n = 427); PORTEC-3 (n = 660)) and five clinical cohorts (n = 1357) were pooled, yielding patients with stage I-III endometrioid and non-endometrioid EC. Tumours were molecularly classified according to the 2020 WHO diagnostic algorithm, with central pathology review by an expert gynaecopathologist. Cause-specific cumulative incidence was estimated using the Aalen-Johansen method and compared using Gray's test. The independent prognostic value of FIGO grading was assessed using multivariable cause-specific Cox regression models. RESULTS: In total, 2621 (83.0%) of the 3158 EC cases were molecularly classified, including 730 (27.9%) MMRd tumours: 405 (55.5%) were low-grade and 325 (44.5%) were high-grade. Median follow-up was 7.2 years. Five-year cumulative incidence of overall recurrence (18.0% vs. 18.8%, p = 0.67) and cancer-specific death (12.3% vs. 14.2%; p = 0.44) did not differ between low- and high-grade MMRd EC. In multivariable analyses, corrected for age, stage, histotype, LVSI and adjuvant treatment, FIGO grading was not independently associated with overall recurrence (HR 0.83 [95%CI 0.56-1.24]; p = 0.37) or cancer-specific death (HR 0.97 [0.62-1.51]; p = 0.89). CONCLUSION: In conclusion, FIGO grading has no prognostic role in MMRd EC and may be omitted in risk stratification and adjuvant treatment decisions.
- Keywords
- Adjuvant therapy; Endometrial cancer; FIGO grade; Mismatch repair deficiency (MMRd); Molecular classification; Prognosis; Recurrence; Risk stratification; Survival; Treatment guidelines; Tumour grading
- Department(s)
- Radiation Oncology
- Publisher's Version
- https://doi.org/10.1016/j.ejca.2026.116885
- Open Access at Publisher's Site
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Creation Date: 2026-07-02 01:34:29
Last Modified: 2026-07-02 01:34:39