Validation of the 2025 ESGO/ESTRO/ESP postoperative risk stratification system in endometrial cancer: A same-cohort comparison with the 2020 molecular classification

초록

Background: Postoperative risk stratification of endometrial cancer has increasingly integrated clinicopathological and molecular features. The clinical value of the 2025 ESGO/ESTRO/ESP update and estrogen receptor (ER)/grade-integrated nonspecific molecular profile (NSMP) sub-classification requires independent real-world evaluation. Methods: We retrospectively included 295 patients with endometrial carcinoma who underwent primary surgery at a tertiary center between 2010 and 2021. Risk groups were assigned according to both the 2020 and 2025 ESGO/ESTRO/ESP systems. The head-to-head prognostic performance was evaluated in 277 patients classifiable under both systems. The primary endpoint was recurrence-free survival (RFS). Results: The 2025 system redistributed patients mainly within the intermediate-risk spectrum. No recurrences occurred in the 30 patients assigned to the 2025 intermediate-risk group. In head-to-head analysis, the 2025 system showed a higher adjusted Harrell's concordance index (0.868, 95% CI 0.826–0.909 vs 0.855, 95% CI 0.810–0.896) and lower adjusted Akaike information criterion (401.3 vs 416.9) than the 2020 system for recurrence prediction. Among the 158 NSMP tumors, high-grade or ER-negative tumors were associated with worse 5-year recurrence-free survival than low-grade ER-positive tumors (48.7% vs. 93.5%) and remained associated with recurrence after adjustment (adjusted hazard ratio 5.53, 95% confidence interval 1.79–17.11). Conclusions: The 2025 ESGO/ESTRO/ESP classification demonstrated better model-level prognostic performance and clinically meaningful patient redistribution, particularly within the intermediate-risk spectrum. The ER/grade-integrated NSMP subclassification supports the biological rationale of the updated framework. © 2026

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