Abstract
A subset of rectal cancer (RC), <5%, exhibits mismatch repair deficiency (dMMR); the remaining are classified as proficient (pMMR). Reported evidence on differences between dMMR and pMMR RC is limited. In this nationwide Dutch study, we compared patients with dMMR and pMMR stage II/III RC based on patient and tumor characteristics, treatment patterns, and associated outcomes. Patients diagnosed between 2015 and 2022 with known mismatch repair status were selected from the Netherlands Cancer Registry. Demographic, tumor, and treatment characteristics were compared in the total cohort. Subsequently, dMMR patients were matched 1:2 to pMMR patients on age, year of diagnosis, clinical tumor stage, and node stage. Overall survival (OS) and event-free survival (EFS) were analyzed using Kaplan-Meier estimates and Cox proportional hazard models. Among 7937 eligible patients, 182 (2.3%) had dMMR RC. These patients were younger and had more poorly differentiated tumors, more variation in histology, more advanced clinical stages, and more B-RAF proto-oncogene serine/threonine kinase mutations. In the total cohort, OS was better for dMMR compared with pMMR (hazard ratio [HR] = 0.62 [95% confidence interval [CI] 0.43-0.91]). In the matched cohort, dMMR continued to exhibit improved OS (HR = 0.54 [95% CI 0.33-0.88]), and demonstrated improved EFS (HR = 0.43 [95% CI 0.29-0.63]) after adjustment for potential confounders. dMMR RC is a rare entity associated with younger age and more advanced stages. Although patients with dMMR RC had significantly improved OS and EFS compared with patients with pMMR RC, immunotherapy may further enhance outcomes. This real-world study provides a basis for future investigations aimed at optimizing therapeutic strategies for patients with dMMR RC.