Neoadjuvant immunotherapy for locally advanced resectable gastric and gastroesophageal junction adenocarcinoma: a systematic review and meta-analysis

Abstract Background and objective Neoadjuvant and perioperative immune checkpoint inhibitor (ICI)-based strategies are increasingly being investigated in locally advanced resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma, but the overall efficacy and safety of these approaches remain uncertain. This systematic review and meta-analysis aimed to evaluate pathological response, surgical outcomes, radiological response, and treatment-related safety of ICI-containing preoperative regimens in this setting. Methods A systematic search of PubMed/MEDLINE, Embase, Cochrane CENTRAL, Web of Science, and Scopus was conducted from 2014 to 2026. Google Scholar was also searched as a supplementary source for gray literature and citation tracking. Studies evaluating neoadjuvant or perioperative ICI-based therapy in adults with locally advanced resectable gastric or GEJ adenocarcinoma were included. Pooled estimates for pathologic complete response (pCR), major pathologic response (MPR), objective response rate (ORR), R0 resection, and safety outcomes were calculated using random-effects models. Results Twenty studies were included. The pooled pCR rate was 22.8% (95% c.i. 18.6% to 27.6%), MPR was 49.5% (95% c.i. 41.8% to 57.1%), ORR was 60.6% (95% c.i. 42.0% to 76.6%), and R0 resection was 97.2% (95% c.i. 94.0% to 98.7%). The pooled rates of grade 3 or higher adverse events, immune-related adverse events, and postoperative surgical complications were 24.0% (95% c.i. 15.6% to 35.2%), 23.2% (95% c.i. 15.4% to 33.5%), and 26.2% (95% c.i. 19.1% to 34.7%), respectively. Conclusion Neoadjuvant or perioperative ICI-based therapy is associated with encouraging pathological response and high R0 resection rates in locally advanced resectable gastric and GEJ adenocarcinoma. However, the available evidence is limited by substantial clinical heterogeneity and immature survival data. Larger randomized studies with longer follow-up are needed to confirm long-term oncologic benefit and better define optimal patient selection.