Prognostic impact of mismatch repair status in early-stage endometrial cancer treated with adjuvant radiation: a multi-institutional analysis

PURPOSE:To report the impact of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial cancer (EEC) who receive adjuvant radiotherapy. METHODS:This is a multi-institutional retrospective cohort study across 11 institutions in North America. Patients with known MMR status and stage I-II EEC status post-surgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariable and multivariable analysis were performed by Cox proportional hazard models for RFS/OS. Statistical analyses were conducted using SPSS version 27. RESULTS:A total of 744 patients with median age at diagnosis of 65 years (Interquartile Range (IQR) 58-71) were included. Most patients were White (69.4%), had FIGO 2009 Stage I (84%) and FIGO grade 1-2 (73%). MMR deficiency (dMMR) was reported in 234 patients (31.5%) while 510 patients (68.5%) had preserved MMR (pMMR). External beam radiation therapy (EBRT) +/- vaginal brachytherapy (VBT) was delivered to 186 patients (25%) while 558 patients (75%) received VBT alone. At a median follow-up of 43.5 months, the estimated crude overall survival (OS) and recurrence free survival (RFS) rates for the entire cohort were 92.5% and 84%, respectively. The MMR status was significantly correlated with RFS. RFS was inferior for dMMR compared to pMMR (74.3% vs. 88.6% p<0.001). However, no difference in OS was seen (90.8% vs. 93.2%, p=0.5). On multivariable analysis, dMMR status was associated with worse RFS (HR 1.86, p=0.001), but not OS. CONCLUSION:MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiotherapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.