Microsatellite instability and immunotherapy: redefining the role of surgery in colorectal cancer

The integration of molecular diagnostics into surgical oncology is redefining the management of colorectal cancer (CRC). Microsatellite instability (MSI) testing and mismatch repair (MMR) analysis have moved from purely prognostic tools to key determinants of therapeutic strategy. In MSI-high (MSI-H) and MMR-deficient (dMMR) tumours, immune checkpoint inhibitors have shown unprecedented pathological response rates, leading to a paradigm shift in non-metastatic CRC. Recently published trials suggest that immunotherapy may alter the timing and extent of resection, while raising new questions about patient selection, surgical planning, and long-term oncological safety. Conversely, microsatellite-stable (MSS) disease remains a therapeutic frontier, with ongoing studies exploring combined immunotherapy regimens. This evolving landscape demands that surgeons develop a deeper understanding of tumour biology and participate actively in translational research. The future of CRC surgery will rely not only on technical excellence but on the ability to integrate molecular knowledge into precise, multidisciplinary treatment algorithms.