Immunotherapy Enables Non-Surgical Management of dMMR/MSI-H Colorectal Cancer

Overview

This systematic review and meta-analysis of 9 studies involving 196 patients demonstrates that non-operative management following immunotherapy in dMMR/MSI-H colorectal cancer yields excellent oncologic outcomes, with local relapse rates near 0%, two-year recurrence-free survival approaching 100%, and organ preservation exceeding 90%. Immunotherapy appears to safely defer or omit surgery in selected patients achieving complete clinical response.

Background

Mismatch repair–deficient (dMMR) or microsatellite instability–high (MSI-H) colorectal cancer (CRC) has shown remarkable responsiveness to immune checkpoint inhibitors (ICIs). Landmark trials have established immunotherapy as first-line treatment in metastatic dMMR/MSI-H CRC, and neoadjuvant immunotherapy has demonstrated high efficacy in locally advanced disease. Emerging evidence suggests that a 'watch-and-wait' strategy after immunotherapy-induced complete clinical response (cCR) may allow organ preservation without compromising oncologic outcomes, challenging the traditional role of surgery.

Data Highlights

Key Findings

• Among 196 patients with dMMR/MSI-H CRC managed non-operatively after immunotherapy, local regrowth was extremely rare (2%).
• Two-year recurrence-free survival consistently ranged from 98% to 100%, with overall survival at 100% in studies with at least 20 months follow-up.
• Organ preservation was achieved in over 90% of patients, with the largest series reporting 96% anorectal preservation.
• Immune checkpoint inhibitor-related toxicities were generally low grade; severe immune-related adverse events were infrequent and manageable.
• Non-operative management after immunotherapy compares favorably to conventional chemoradiotherapy approaches, which have lower organ preservation rates and higher recurrence risk.
• Evidence primarily derives from rectal cancer, but preliminary data suggest feasibility in selected colon cancer patients as well.

Clinical Implications

For patients with dMMR/MSI-H colorectal cancer who achieve a complete clinical response after immunotherapy, a non-operative 'watch-and-wait' approach may be considered to preserve organ function without compromising oncologic outcomes. Careful patient selection, standardized response assessment, and close surveillance are essential. This strategy may reduce surgical morbidity and improve quality of life, but longer-term data and prospective trials are needed to confirm durability and safety.

Conclusion

Immunotherapy enables durable remission and high rates of organ preservation in dMMR/MSI-H colorectal cancer, supporting the potential to safely omit surgery in selected patients achieving complete clinical response. Further prospective studies are warranted to optimize protocols and validate long-term outcomes.

References

1. Cercek et al. 2022–2025 -- Immunotherapy in dMMR/MSI-H colorectal cancer
2. KEYNOTE and CheckMate trials -- Immune checkpoint inhibitors in metastatic CRC
3. Memorial Sloan Kettering Cancer Center series -- Non-operative management outcomes
4. MD Anderson cohort -- Disease control after immunotherapy discontinuation