Incidence and Outcomes of Patients With Mismatch Repair Deficient Rectal Cancer Operated in 2016: A Nationwide Cohort From The Netherlands.

Introduction: Data regarding the incidence and outcomes of mismatch repair deficient (dMMR) rectal cancer is limited. This study characterizes dMMR rectal cancer patients, comparing response after neoadjuvant radiotherapy and oncological outcomes to mismatch repair proficient (pMMR) rectal cancer patients.

Method: A retrospective cross-sectional cohort study was conducted in 67 Dutch centers. Data including patient and tumor characteristics, radiological and pathological reports and oncological follow-up outcomes were gathered from documentation in electronic patient files for patients who underwent a curative resection for primary rectal cancer in 2016. MMR-status was verified in pathology reports from immunohistochemistry or PCR microsatellite instability testing.

Results: MMR-status was determined in 1645 (54.9%) of 3001 stage I-IV rectal cancer patients, of which 46 (2.8%) were dMMR. Median follow up was 50 months (IQR 38-55). MMR-status was determined more often in younger patients. DMMR tumors were more locally advanced (cT4 23.9% vs. 8.8%, P = .010), and more distally located (mean distance to anorectal junction 3.6 cm vs. 5.3 cm, P = .004) than pMMR tumors. While radiological response after neoadjuvant (chemo)radiotherapy was similar, pathological complete response was significantly higher in dMMR compared to pMMR tumors (24.0% vs. 10.0%, P = .039). Four-year local recurrence, distant metastases, cancer-specific or overall survival rate between patients with dMMR or pMMR tumors were similar.

Conclusion: In this population-based cohort, 2.8% of rectal cancers in which MMR-status was determined were subtyped as dMMR. Surprisingly, dMMR was associated with higher pathological complete response rate to neoadjuvant (chemo) radiotherapy than pMMR. MMR-status did not impact oncological outcomes.