J.Jpn. Surg. Soc.. 127(2): 178-184, 2026

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Feature topic

PREOPERATIVE IMMUNE CHECKPOINT INHIBITORS FOR COLORECTAL CANCER

Preoperative immune checkpoint inhibitors (ICIs) are rapidly reshaping the perioperative management of colorectal cancer. In microsatellite instability high/deficient mismatch repair (MSI-H/dMMR) rectal cancer, neoadjuvant PD-1 blockade achieves unprecedented clinical complete responses, enabling nonoperative management with durable control; contemporary Western guidelines now endorse ICIs in this setting. In MSI-H/dMMR colon cancer, short-course dual ICI (nivolumab plus ipilimumab) yields very high major and pathologic complete response rates, supporting broad applicability of neoadjuvant immunotherapy beyond the rectum. Conversely, for microsatellite stable/proficient MMR (MSS/pMMR) disease, ICIs alone remain insufficient; immunotherapy-based total neoadjuvant therapy improves complete response rates and facilitates organ preservation. Across settings, emerging biomarkers, including ctDNA dynamics and tumor–immune profiling, may refine selection and surveillance. Finally, detection of MSI-H/dMMR mandates genetic management: timely referral; germline testing for Lynch syndrome; tailored surveillance; and care for relatives. This review summarizes current evidence and ongoing trials of preoperative ICIs for rectal and colon cancer, outlines practical considerations for nonoperative strategies, and highlights priorities for standardization of response assessment, optimization of treatment sequencing and duration, and integration of precision biomarkers into surgical decision-making.

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