Does MMR status in endometrial cancer influence response to adjuvant therapy?

Mismatch repair (MMR) deficiency occurs in 20-40% of endometrial cancers but its therapeutic implication remains uncertain. Our objective was to compare clinical outcomes after adjuvant therapy between MMR deficient and proficient endometrial cancers from a population-based study.

This was a retrospective population-based cohort study of all endometrial cancers from the Vancouver Coastal Health authority region from 2011 to 2016, for which adjuvant therapy (radiotherapy and/or chemotherapy) was administered. Primary outcome measure was recurrence rates, expressed per 100 person-years (p100 py). Progression free survival (PFS) and overall survival (OS) rates were compared using Kaplan-Meier method and log-rank tests, and covariates were evaluated using Cox proportional hazards regression.

There were 535 patients who received adjuvant therapy (radiotherapy and/or chemotherapy), including 162 (30.3%) and 373 (69.7%) with MMR-deficient and proficient tumors, respectively. Demographic variables were similar except MMR-deficient patients were younger (62.0 vs. 64.8, p = 0.01). Patients with MMR-deficient tumors were more likely to have endometrioid histotype (85.8% vs. 61.4%), more likely to have Stage I disease (62.3% vs 54.7%), and LVSI (65.4% vs. 53.4%) compared to those with MMR-proficient tumors. There was a trend for MMR-proficient group to have higher recurrence rates (10.7 p100 py vs 5.9 p100 py) and MMR deficiency was associated with better OS and PFS, but on multivariable analysis, MMR status was no longer significant.

Women with MMR-deficient endometrial cancers who receive adjuvant therapy have a lower rate of recurrence compared to those with MMR-proficient cancers. However, on multivariable analysis, MMR status does not remain associated with differences in PFS or OS.