Prognostic Impact of Mismatch Repair Deficiency on Stage I-II Endometrioid Endometrial Cancer Treated with Adjuvant Radiation Therapy: A Multi-Institutional Analysis

Abstract

To report the impact of mismatch repair (MMR) status on outcomes in patients with stage I-II endometrioid endometrial cancer (EEC). This is a multi-institutional retrospective cohort study across 11 institutions. Preliminary data from 7 centers is available for analysis. Patients with known MMR status and stage I-II EEC status post-surgical staging treated with adjuvant radiation therapy were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed by Cox proportional hazard models for OS/RFS. Statistical analyses were conducted using statistical software. A total of 573 patients with median age at diagnosis of 65 years (Interquartile Range (IQR) 58-71) were eligible. Most patients were White (79%), had FIGO 2009 Stage I (89.7%) and FIGO grade 1-2 (74.7%). MMR deficiency (dMMR) was reported in 191 patients (33%) while 382 patients (67%) had preserved MMR (pMMR). External beam radiation therapy (EBRT) +/- vaginal brachytherapy (VBT) was delivered to 124 patients (21.6%) while 449 patients (78.4%) received VBT alone. After a median follow-up of 41 months ((IQR) 28-60 months), the estimated OS and RFS rates for the entire cohort were 95.1% and 85%, respectively. On univariate analysis, age >65 (p < 0.001), grade 3 (p < 0.001), presence of lymphovascular space invasion (LVSI) (p = 0.039) and deep myometrial invasion (p = 0.03) were associated with worse OS. The OS was inferior in the dMMR group, however, it did not reach significance (92% vs 96.1%, p = 0.06). On multivariate analysis, older age (p < 0.001) and grade 3 (p = 0.002) were the only predictors for worse OS. On univariate analysis for RFS, age >65 (p = 0.02), grade 3 (p = 0.018) and dMMR (72.9% vs 91%, p < 0.001) were associated with worse RFS. On multivariate analysis, age >65 (p = 0.015) and dMMR (p < 0.001) were significant predictors of worse RFS. Preliminary data from 7 out of 11 participating institutions showed that dMMR status leads to significantly decreased RFS in patients with early-stage EEC. While awaiting the results of NRG GYN020 and RAINBO prospective trials, this large study suggests that treatment intensification could be warranted in patients with dMMR early-stage EEC.