Neoadjuvant Immunotherapy in Localized dMMR/MSI-H Colon Cancer: A Systematic Review of Pathological Response and Surgical Outcomes.

Abstract

Background: Neoadjuvant immune checkpoint inhibition is increasingly being investigated in localized mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) colon cancer, but evidence remains immature and often combined with broader cohorts.

Methods: We reviewed prospective interventional studies of neoadjuvant immune checkpoint inhibition in adults with localized, non-metastatic dMMR/MSI-H colon cancer. The Ovid MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov databases and reference lists were searched to 12 June 2026. Studies were eligible when colon-specific pathological response outcomes were reported or extractable. Primary outcomes were pathological complete response (pCR) and major pathological response (MPR). Secondary outcomes included surgical feasibility, R0 resection, delay, morbidity, adverse events, recurrence, and survival.

Results: Six studies were included: NICHE, NICHE-2, NICHE-3, RESET-C, IMHOTEP, and IBI310/sintilimab. pCR ranged from 44 to 78.4% and MPR from 57 to 95%, varying by regimen, denominator, and definition. NICHE-based dual-checkpoint studies reported pCR rates of 60-68% and MPR rates of 92-95%. Pembrolizumab-based studies reported pCR rates of 44-62.7%. The only randomized comparative study favored CTLA-4 plus programmed cell death protein-1 blockade over programmed cell death protein-1 blockade alone. Most patients proceeded to colectomy, with high R0 resection rates where reported. Severe treatment-related or immune-related adverse events occurred, including rare grade 5 events. Follow-up ranged from 8.1 to 26 months; recurrence was uncommon and survival outcomes immature.

Conclusions: Neoadjuvant immune checkpoint inhibition demonstrates substantial pathological activity and apparent surgical feasibility in selected localized dMMR/MSI-H colon cancer. Longer follow-up and comparative trials are needed to define regimen, timing, patient selection, and durable oncological benefit.