Objective:

To address decision-making challenges following immunotherapy in patients with metastatic colorectal cancer (mCRC) characterized by deficient DNA mismatch repair (dMMR) and microsatellite instability (MSI), highlighting the significance of these challenges in clinical practice.

Key Findings:

• ICI treatment has shown unprecedented efficacy in dMMR/MSI mCRC, with potential for long-term disease control and implications for treatment strategies.
• Optimal treatment duration remains unclear; evidence suggests shorter durations may not compromise efficacy, impacting patient management.
• Conventional imaging lacks specificity in distinguishing between fibrotic responses and viable disease, complicating treatment decisions and necessitating improved diagnostic tools.

Interpretation:

The rapid and durable responses to ICI in MSI mCRC indicate a shift in treatment paradigms, necessitating careful consideration of surgical interventions for residual lesions and their impact on patient outcomes.

Limitations:

• Current imaging modalities may not accurately differentiate between types of tumor responses, potentially leading to mismanagement.
• Lack of prospective randomized trials on optimal treatment duration and management of residual tumors highlights the need for further research.

Conclusion:

The potential for cure with ICI in dMMR/MSI mCRC should influence decisions regarding surgery for residual lesions, underscoring the need for improved diagnostic tools and treatment strategies, and emphasizing the importance of ongoing research.