Neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy in locally advanced gastric cancer: A systematic review and...

Neoadjuvant immunochemotherapy (nICT) has emerged as a promising perioperative strategy for locally advanced gastric and gastroesophageal junction cancer (LAGC/EGJC), yet its survival benefit beyond pathological response and optimal patient selection remain uncertain. We conducted a systematic review and meta-analysis to evaluate the efficacy, safety, and biomarker stratification of nICT compared with neoadjuvant chemotherapy (nCT). PubMed, Embase, Web of Science, and the Cochrane Library were searched through August 30, 2025. Comparative studies of nICT versus nCT and single-arm nICT cohorts were included. Overall survival (OS) and recurrence-free survival (RFS) were primary outcomes. Fifteen comparative studies and thirty-four single-arm or biomarker datasets were included. Compared with nCT, nICT significantly improved OS (HR = 0.80, 95 % CI 0.70-0.92) and RFS (HR = 0.78, 95 % CI 0.69-0.87), and achieved higher pathological complete response, major pathological response, and R0 resection rates. Although treatment-related adverse events were more frequent with nICT, postoperative recovery and complication rates were comparable. Single-arm analyses showed pooled pathological complete and major pathological response rates of approximately 20 % and 43 %, with encouraging 2-year OS and RFS. Biomarker analyses demonstrated enrichment of pathological response in patients with PD-L1 CPS ≥ 1/≥ 5 and dMMR/MSI-H, whereas tumor mutational burden and Epstein-Barr virus status showed inconsistent discriminatory value. Meta-regression revealed no significant effect modification. Overall, nICT provides pathological and early survival improvement without compromising perioperative safety, supporting its integration into perioperative strategies for LAGC/EGJC.