To investigate the appropriate timing of radiotherapy (RT) after hysterectomy in women with early-stage endometrial cancer (EC). We analyzed the data of 1,062 patients with early-stage EC who underwent postoperative RT at our hospital between April 1999 and November 2020. Restricted cubic spline were used to explore the relationship between the surgery-radiotherapy interval (SRI) and local recurrence-free survival (LRFS). The maximally selected rank statistics method was used to identify the optimal threshold for SRI. The overall survival (OS), disease-free survival (DFS), LRFS, and distant metastasis-free survival (DMFS) rates were estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox proportional hazards regression. In entire cohort, patients with SRI ≥42 days had worse survival. In multivariate analysis, SRI was an independent prognostic factor for OS (p=0.011), DFS (p=0.019), LRFS (p=0.013) and DMFS (p=0.050). However, in piecewise Cox regression, the significance of SRI for DMFS disappeared. In the subgroup analysis, the optimal cut-off value for SRI in the high-intermediate risk (HIR) and high-risk (HR) groups was 33 days. Multivariate analysis showed that SRI was an independent prognostic factor only for LRFS (p=0.033) and marginally associated with OS (p=0.055). The timing of postoperative RT is crucial in patients with early-stage EC. Adjuvant RT should be initiated as soon as the vaginal cuff is healed, while for HIR and HR patients, it should be initiated within 33 days.
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