Neoadjuvant versus Adjuvant Immunotherapy in MSI-H/dMMR Early Colorectal Cancer: A Value-Conscious Re-examination of Dogma

The management of early-stage colorectal cancer (CRC) is undergoing a paradigm shift driven by advances in immunotherapy, particularly for tumors characterized by microsatellite instability-high (MSI-H) or mismatch repair deficiency (dMMR). Representing approximately 15% of non-metastatic CRC, this biologically distinct subgroup is intrinsically resistant to fluoropyrimidine-based chemotherapy yet uniquely sensitive to immune checkpoint inhibition. This review critically examines the emerging evidence supporting neoadjuvant versus adjuvant immunotherapy strategies in early-stage MSI-H/dMMR colon cancer, drawing on data from FOxTROT, NICHE-2, and ATOMIC. We argue that neoadjuvant immunotherapy is biologically more rational, clinically effective, and value-conscious—particularly relevant in resource-limited settings—while acknowledging that definitive practice change will require randomized comparative trials.