Perioperative Chemoimmunotherapy vs. Chemotherapy Alone for Gastroesophageal Cancer: A Systematic Review and Meta-Analysis.

PURPOSE: To systematically evaluate the efficacy and safety of adding immune checkpoint inhibitors (ICIs) to perioperative or neoadjuvant chemotherapy versus chemotherapy alone in resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma. METHODS: PubMed, Embase, and Cochrane CENTRAL were searched through July 31, 2025. Outcomes included event-free survival (EFS), pathologic complete response (pCR), overall survival (OS), disease-free survival (DFS), major pathologic response (MPR), R0 resection rate, and safety. Hazard ratios (HRs) and risk ratios (RRs) were pooled with random-effects models. RESULTS: Twenty studies (6 randomized controlled trials and 14 non-randomized comparative studies; 5,317 patients) were analyzed. Immunochemotherapy improved EFS (HR, 0.76; 95% CI, 0.66–0.87) and DFS (HR, 0.69; 95% CI, 0.60–0.78), with a nonsignificant trend for OS (HR, 0.81; 95% CI, 0.64–1.02). No significant effect modification by treatment timing (neoadjuvant-only vs. perioperative) was observed. Pathologic outcomes favored immunochemotherapy: pCR (RR, 2.93; 95% CI, 2.39–3.59) and MPR (RR, 1.59; 95% CI, 1.34–1.90). R0 resection rates were marginally higher (RR, 1.02; 95% CI, 1.00–1.03). Rates of grade ≥ 3 treatment-related adverse events (RR, 1.07; 95% CI, 0.97–1.17) and severe postoperative complications (RR, 1.00; 95% CI, 0.65–1.53) were comparable between groups. The pCR benefit was most pronounced in microsatellite instability–high tumors (RR, 5.18; 95% CI, 2.43–11.05). CONCLUSION: Adding ICIs to perioperative or neoadjuvant chemotherapy for resectable gastric and GEJ adenocarcinoma improves EFS, DFS, and pathological responses, without increasing severe toxicity or postoperative morbidity. R0 resection differences appeared clinically limited. MSI-H status emerged as a potential predictor of benefit.