Immunotherapy in Localized Colorectal Cancer: Current Practice and Future Directions.

Area of Science:

• Oncology
• Immunotherapy
• Gastroenterology

Background:

• Immune checkpoint inhibitors (ICIs) have revolutionized localized colorectal cancer (CRC) treatment, especially for mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) subtypes.
• Early-stage CRC management is evolving with immunotherapy, showing significant promise.

Purpose of the Study:

• To review current clinical evidence and evolving paradigms of immunotherapy in early-stage CRC.
• To identify critical questions and future directions for ICI therapy in CRC.

Main Methods:

• Review of current clinical evidence and evolving paradigms of immunotherapy in early-stage CRC.
• Evaluation of neoadjuvant immunotherapy efficacy in localized MSI-H colon and rectal cancers.
• Assessment of circulating tumor DNA (ctDNA) as a biomarker for molecular residual disease monitoring.

Main Results:

• Neoadjuvant immunotherapy demonstrates unprecedented efficacy in localized MSI-H colon and rectal cancers, with high rates of pathologic complete responses.
• Nonoperative management is a viable, organ-preserving standard for selected MSI-H rectal cancer patients.
• Significant unmet need exists for extending ICI benefits to microsatellite-stable (MSS) CRC.

Conclusions:

• Immunotherapy has transformed early-stage MSI-H CRC treatment, enabling nonoperative management in select rectal cancer cases.
• Further research is needed on optimal ICI regimens, duration, and the role of ctDNA.
• Developing strategies for MSS CRC and employing precision de-escalation and biomarker-driven trials are crucial for future progress.