Immunotherapy With Pembrolizumab for Resectable dMMR/MSI-H Stage III Colon Cancer: A Case of Personalized, Precision...

Colorectal cancer (CRC) with deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) status represents a highly immunogenic subset that responds well to immune checkpoint inhibitors (ICIs). However, the role of ICIs in resectable, early-stage CRC remains under investigation. We report the case of an 81-year-old woman diagnosed with stage III adenocarcinoma of the right colon, who declined surgery. Immunohistochemistry revealed loss of MLH1 and PMS2, consistent with dMMR. Tumor genomic profiling demonstrated MSI-H, high tumor mutational burden, BRAF V600E, and BRCA2 mutation. Germline testing was negative for BRCA and Lynch syndrome-associated mutations. The patient was treated with neoadjuvant pembrolizumab. After 4 months, mesenteric lymphadenopathy resolved, but focal colonic thickening persisted. The patient again declined surgery. At 10 months of pembrolizumab therapy, PET/computed tomography and colonoscopy showed no residual disease. She developed immune-related adrenal insufficiency, managed with corticosteroids. This case demonstrates complete clinical remission of resectable colon cancer with pembrolizumab alone in a patient with somatic dMMR/MSI-H, BRAF V600E, and BRCA2 mutations. It supports the hypothesis that early use of ICIs-prior to metastatic progression and immune escape-may enhance efficacy. This report highlights the potential for personalized, surgery-sparing treatment strategies in genomically selected CRC patients.