Neoadjuvant immune checkpoint inhibitors for localized dMMR/MSI-H gastric cancer: a meta-analysis

Early studies indicate that neoadjuvant immune checkpoint inhibitors (ICIs) induce high rates of tumor regression in localized deficient mismatch repair (dMMR) and microsatellite instability-high (MSI-H) gastric and gastroesophageal junction (GEJ) cancers, raising interest in nonoperative management (NOM). Most available data, however, come from small, nonrandomized cohorts. A systematic synthesis was undertaken to better characterize efficacy and safety outcomes.

A systematic search of PubMed, EMBASE, Scopus, Web of Science, and Cochrane Reviews was conducted from inception through June 2025 for prospective or retrospective studies of neoadjuvant ICIs in localized dMMR/MSI-H gastric or GEJ cancers reporting at least one prespecified outcome. Two reviewers independently extracted data and assessed study quality according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled estimates were calculated using a DerSimonian and Laird random-effects model, and NOM outcomes were qualitatively summarized.

Twenty studies (396 patients) met inclusion criteria; three used dual ICI therapy, and the remainder used ICI alone or with chemotherapy. Overall, 320 patients (81.0%) underwent surgical resection. The pooled pathologic complete response (pCR) rate was 41.9% [95% confidence interval (CI) 33.2% to 51.1%], clinical complete response 63.8% (95% CI 45.6% to 78.8%), major pathologic response 64.2% (95% CI 49.1% to 76.9%), and grade 3-4 immune-related adverse events 6.7% (95% CI 1.7% to 13.8%). pCR was higher with treatment duration ≥3 months compared with <3 months [50.2% (95% CI 42.3% to 58.7%) versus 28.4% (95% CI 18.9% to 40.2%), χ² = 8.84, P = 0.003]. Forty-four patients were managed nonoperatively, with two early local regrowths at median follow-up ranging from 11.5 to 28 months.

Neoadjuvant ICIs are associated with favorable efficacy and safety in localized dMMR/MSI-H gastric and GEJ cancers. Longer neoadjuvant exposure (≥3 months) may improve pCR rates. Larger prospective studies are needed to define optimal treatment duration and the role of organ-preserving strategies such as NOM.