Exploring the molecular classification-based personalized treatment decision-making in FIGO stage I–III endometrial carcinoma after surgery: a population-based real-world study
Lingxia Xin, Kang Ren, Zihan Yan, Yunlong Sheng, Yaqi Wang, Yihan Zhang, Xiaorong Hou, Huanwen Wu, Fuquan ZhangBackground:
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.