Integrated mortality and oncological risk stratification predicts survival in stage I–III dMMR colon cancer: A retrospective cohort study

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Background Immune checkpoint inhibitors (ICIs) show promise in the treatment of deficient mismatch repair (dMMR) colon cancer, prompting interest in non-surgical alternatives for localized disease. To guide treatment decisions, it is essential to understand patient heterogeneity. This study aimed to describe the clinical characteristics of patients with localized (UICC I–III) dMMR colon cancer in a large, national Danish cohort and to investigate the associations between predicted one-year postoperative mortality risk, oncological risk, and survival outcomes. Material and methods This retrospective cohort study included patients who underwent primary curative-intent surgery without neoadjuvant therapy for clinical stage I–III dMMR colon cancer between 2016 and 2019. Patients were identified through the Danish Colorectal Cancer Group database. To compare outcomes across different estimated risk levels, the patients were stratified into low-to-moderate (≤15%) or high (>15%) predicted one-year mortality groups. They were further divided into low- or high-oncological risk groups based on TNM classification. Results Patients with high predicted mortality risk had higher rates of underweight status, comorbidities, and postoperative complications. Kaplan-Meier curves demonstrated significantly lower overall survival in high-risk patients, particularly within the first three postoperative years. In Cox proportional hazards analysis, high predicted one-year mortality risk remained strongly associated with reduced overall survival. Recurrence-free survival was shortest among patients classified as high risk for both predicted mortality and oncological risk. Conclusion In this national cohort of patients with dMMR colon cancer, a high predicted one-year mortality risk was strongly associated with poorer overall survival, regardless of tumor stage. In contrast, recurrence-related outcomes were primarily driven by oncological risk, while predicted one-year mortality risk provided complementary prognostic information. The shortest recurrence-free survival was observed in patients classified as high risk on both dimensions.