Patterns of failure after primary treatment and prognostic factors in stage I, grade 2-3 endometrial cancer

Purpose: This study aimed to characterize recurrence patterns and identify prognostic factors in patients with stage I, grade 2-3 endometrioid endometrial cancer. Materials and Methods: We retrospectively analyzed 298 patients with 2009 International Federation of Gynecology and Obstetrics stage IA-IB, grade 2-3 endometrioid endometrial cancer treated with curative intent between 2010 and 2020. The primary endpoint was recurrence-free interval (RFI), defined as the time from surgery to documented recurrence or last follow-up. Cox regression analyses were performed to identify prognostic factors. Recursive partitioning analysis (RPA) was used for risk stratification. Results: With a median follow-up of 80.1 months, 40 patients (13.4%) experienced recurrence. Distant recurrence was the most common recurrence pattern (n = 28, 9.4%), followed by vaginal recurrence (n = 10, 3.4%), para-aortic recurrence (n = 8, 2.7%) and pelvic recurrence (n = 7, 2.3%). In multivariable analysis, older age (hazard ratio [HR] per year, 1.05; p = 0.004), tumor size ≥4 cm (HR, 2.28; p = 0.027), grade 3 histology (HR, 2.20; p = 0.022), and stage IB disease (HR, 2.31; p = 0.043) were significantly associated with inferior RFI. Estrogen receptor (ER) negativity was associated with inferior RFI in exploratory univariable analysis (HR, 5.10; p < 0.001). An age- and stage-based RPA model classified patients into three groups with significantly different RFI (p < 0.001). Post hoc analysis suggested a higher recurrence proportion among ER-negative patients aged ≤70 years with stage IB disease. Conclusion: Recurrence in stage I, grade 2-3 endometrioid endometrial cancer was infrequent, but distant metastasis was the most common recurrence pattern. Conventional clinicopathologic factors provided clinically useful risk stratification, while ER status may offer additional prognostic information in selected subgroups.