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Exploring the molecular classification-based personalized treatment decision-making in FIGO stage I-III endometrial
Lingxia Xin1, Kang Ren1, Zihan Yan1
1Department of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Background:
Robust real-world evidence supporting the clinical utility of molecular classification in endometrial carcinoma (EC) remains limited.
Objectives:
To investigate the molecular classification-based personalized treatment decision-making for EC by presenting real-world data, including survival outcomes and failure patterns.
Methods:
This retrospective cohort study included patients with International Federation of Gynecology and Obstetrics (FIGO) stage I-III EC who underwent initial surgery and had available molecular classification at Peking Union Medical College Hospital, between December 2017 and April 2025. The primary endpoint was disease-free survival (DFS). We evaluated survival outcomes, visualized dynamic annual hazard rates (AHRs), and compared failure patterns across subgroups. Independent prognostic factors were identified using Cox regression analyses.
Results:
Between December 2017 and April 2025, 267 eligible patients were evaluated. The median age was 55 years, and the median follow-up was 31.10 months. NSMP was the most common molecular subtype (46.8%), followed by MMRd (27.7%), POLEmut (13.1%), and p53abn (12.4%). Endometrioid carcinoma G1-2 was the predominant histological type overall (74.5%). According to FIGO, the 2009 criteria, the stage distribution was as follows: IA (66.7%), IB (20.6%), II (4.5%), and III (12.2%). Restaging under the FIGO 2023 system resulted in upstaging in 20.2% and downstaging in 2.6% of patients. Most patients (56.6%) were classified as low-risk per the ESGO-ESTRO-ESP 2025 risk classification. Although observation alone was used in 45.7% of the entire cohort, intensified treatment was administered to 33.3% of the p53abn subgroup. Excellent 3-year overall survival (OS, 99.2%) and (DFS, 88.4%) were observed in the entire cohort. The p53abn group exhibited the highest recurrence rate (30.3%), frequently presenting as simultaneous multi-site recurrences. No recurrences were observed in the POLEmut group. The p53abn group exhibited the highest recurrence hazard rate (peak: 2.2% at 16.8 months), followed by the MMRd group (peak: 0.8% at 14.0 months) and the NSMP group (peak: 0.3% at 21.0 months). Both the ESGO-ESTRO-ESP 2025 risk classification and FIGO 2023 staging were independent prognostic factors for recurrence.
Conclusion:
This study provides evidence that molecular classification-based personalized treatment decision-making is feasible and can yield excellent survival outcomes in patients with stage I-III EC.
