Prognostic Effect of Mismatch Repair Status in Early-Stage Endometrial Cancer Treated With Adjuvant Radiation: A Multi-institutional Analysis

Int J Radiat Oncol Biol Phys. 2024 Jul 15;119(4):1158-1165. doi: 10.1016/j.ijrobp.2024.01.203. Epub 2024 Jan 20.

Abstract

Purpose: The aim of this work was to report the effect of mismatch repair (MMR) status on outcomes of patients with stage I-II endometrioid endometrial adenocarcinoma (EEC) who receive adjuvant radiation therapy.

Methods and materials: 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 postsurgical staging were included. Overall survival (OS) and recurrence-free survival (RFS) rates were estimated via the Kaplan-Meier method. Univariable and multivariable analyses were performed via Cox proportional hazard models for RFS and OS. Statistical analyses were conducted using SPSS version 27.

Results: In total, 744 patients with a median age at diagnosis of 65 years (IQR, 58-71) were included. Most patients were White (69.4%) and had Federation of Obstetrics and Gynecology 2009 stage I (84%) and Federation of Obstetrics and Gynecology grade 1 to 2 (73%). MMR deficiency was reported in 234 patients (31.5%), whereas 510 patients (68.5%) had preserved MMR. External beam radiation therapy with or without vaginal brachytherapy was delivered to 186 patients (25%), whereas 558 patients (75%) received vaginal brachytherapy alone. At a median follow-up of 43.5 months, the estimated crude OS and RFS rates for the entire cohort were 92.5% and 84%, respectively. MMR status was significantly correlated with RFS. RFS was inferior for MMR deficiency compared with preserved MMR (74.3% vs 88.6%, P < .001). However, no difference in OS was seen (90.8% vs 93.2%, P = .5). On multivariable analysis, MMR deficiency status was associated with worse RFS (hazard ratio, 1.86; P = .001) but not OS.

Conclusions: MMR status was independently associated with RFS but not OS in patients with early-stage EEC who were treated with adjuvant radiation therapy. These findings suggest that differential approaches to surveillance and/or treatment based on MMR status could be warranted.

Publication types

  • Multicenter Study

MeSH terms

  • Aged
  • Brachytherapy
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / mortality
  • Carcinoma, Endometrioid / pathology
  • Carcinoma, Endometrioid / radiotherapy
  • DNA Mismatch Repair*
  • Disease-Free Survival
  • Endometrial Neoplasms* / genetics
  • Endometrial Neoplasms* / mortality
  • Endometrial Neoplasms* / pathology
  • Endometrial Neoplasms* / radiotherapy
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Staging*
  • Prognosis
  • Proportional Hazards Models
  • Radiotherapy, Adjuvant
  • Retrospective Studies