Limited prognostic impact of mismatch repair status in high-intermediate risk early-stage endometrial cancer receiving adjuvant radiotherapy: a retrospective cohort study.

OBJECTIVE: To investigate whether mismatch repair deficiency (dMMR) affects treatment outcomes in early-stage high-intermediate risk (HIR) endometrial cancer (EC) patients receiving adjuvant therapy. METHODS: This retrospective study included patients with 2009 International Federation of Gynecology and Obstetrics stage I-II EC who underwent complete staging surgery from August 2006 to December 2022 at Kaohsiung Chang Gung Memorial Hospital. HIR stage I EC was defined using PORTEC and GOG-99 criteria. Stage II disease was considered low risk if meeting all criteria: endometrioid histology, grade 1-2, absence of lymphovascular invasion, and no lymph node involvement. Patients received adjuvant external beam radiation therapy (EBRT) or vaginal brachytherapy. Clinicopathological characteristics and 5-year disease-free survival (DFS) were analyzed. RESULTS: Among the 137 included patients with a median follow-up of 55 months, MMR status was available for all cases, and 32.1% were classified as dMMR. In 115 patients receiving adjuvant radiation, dMMR was associated with higher parity (97.6% vs. 71.2%, p=0.001) and showed a trend toward higher ER expression (170.5 vs. 136.7, p=0.126). Five-year DFS was comparable between MMR-proficient (pMMR) and dMMR groups overall (90.3% vs. 88.6%, p=0.881), in radiation-only patients (91.9% vs. 90.2%, p=0.846), and EBRT-only patients (85.4% vs. 85.2%, p=0.908). Cox regression revealed no significant predictors of DFS including MMR status. CONCLUSION: MMR status did not impact survival outcomes in early-stage HIR EC patients receiving adjuvant therapy, suggesting limited prognostic value and questioning routine MMR testing cost-effectiveness in this subgroup.