Neoadjuvant PD-1-Based Immunotherapy in Localized dMMR/MSI-H Colorectal Cancer: A Systematic Review and Arm-Based...

Area of Science:

• Oncology
• Immunotherapy
• Gastrointestinal Oncology

Background:

• Deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) colorectal cancer (CRC) exhibit sensitivity to immune checkpoint blockade.
• Neoadjuvant PD-1-based immunotherapy is being investigated for localized dMMR/MSI-H CRC.

Purpose of the Study:

• To evaluate the efficacy, safety, and clinical maturity of neoadjuvant PD-1-based immunotherapy in localized dMMR/MSI-H CRC.
• To systematically review prospective studies assessing PD-1 inhibitors in this patient population.

Main Methods:

• PRISMA-compliant systematic review of prospective studies.
• Pooled analysis of pathologic complete response (pCR) and major pathologic response (MPR) using random-effects models.
• Evaluation of immune-related adverse events (irAEs), surgery rates, and clinical outcomes.

Main Results:

• Pooled pCR rate was 0.65 (95% CI, 0.54-0.74) and pooled MPR rate was 0.89 (95% CI, 0.79-0.94).
• Any-grade irAEs occurred in 0.54 (95% CI, 0.36-0.71), with grade ≥3 irAEs in 0.06 (95% CI, 0.04-0.10).
• High pooled surgery proportion (0.96) noted, often protocol-mandated; promising organ preservation in rectal cancer cohorts.

Conclusions:

• Neoadjuvant PD-1 immunotherapy is a promising strategy for localized dMMR/MSI-H CRC.
• Early-phase evidence, indirect comparisons, and limited follow-up restrict definitive conclusions for routine adoption.