First-Line Therapy for MSI-H/dMMR Colorectal Cancer Stage I

Rationale for Immunotherapy in MSI-H/dMMR CRC

• Immunotherapy has demonstrated superior outcomes in MSI-H/dMMR colorectal cancer patients compared to conventional chemotherapy, with significant improvements in progression-free survival and overall survival 2
• The 2024 ASCO guidelines provide a strong recommendation for immunotherapy in MSI-H/dMMR rectal cancers (evidence quality: low; strength of recommendation: strong) 1

Specific Treatment Recommendations

• PD-1 inhibitors (pembrolizumab, nivolumab) are the preferred first-line agents for MSI-H/dMMR CRC stage I 2, 3
• For patients who cannot receive immunotherapy due to contraindications, surgical resection alone may be sufficient for stage I disease 1
• Fluoropyrimidine-based chemotherapy can be considered, though historically less effective in dMMR tumors 1

Clinical Evidence Supporting Immunotherapy

• Multiple studies have demonstrated high response rates to PD-1 inhibitors in MSI-H/dMMR colorectal cancer 3

Important Considerations

• MMR/MSI testing should be performed on all colorectal cancer specimens to identify patients eligible for immunotherapy 3
• Patients with stage I MSI-H/dMMR CRC have excellent prognosis compared to more advanced stages, but immunotherapy is still preferred due to its superior efficacy and favorable safety profile 4
• For patients with contraindications to immunotherapy, surgical resection remains the cornerstone of treatment for stage I disease 1

Treatment Algorithm

• If confirmed MSI-H/dMMR, first choice is PD-1 inhibitor immunotherapy (pembrolizumab or nivolumab) 2, 3
• If contraindicated, proceed with surgical resection alone 1
• Continue immunotherapy for recommended duration per specific agent guidelines 3