Neoadjuvant PD-1 inhibitors plus chemotherapy versus neoadjuvant chemotherapy alone in patients with resectable locally advanced gastric cancer

Neoadjuvant chemotherapy improves downstaging and survival in locally advanced gastric or esophagogastric junction adenocarcinoma (LAGC/EGJC), but the incremental benefit of adding programmed death-1 (PD-1) blockade and pragmatic perioperative biomarkers remain uncertain. We conducted a retrospective cohort of patients with clinically staged cT2N + M0 or cT3–4bNanyM0 (IIa–IVa) LAGC/EGJC who received neoadjuvant PD-1 inhibitor plus chemotherapy or chemotherapy alone, followed by D2 gastrectomy. After one-to-one propensity score matching, pathological response, radiologic response, recurrence-free survival (RFS), overall survival (OS), and safety were compared between the two groups. Exploratory analyses assessed PD-L1 combined positive score (CPS), mismatch repair (MMR) status, blood-based indices (NLR, PLR, SII, PNI). From January 2018 to December 2024, 360 patients were analyzed (n = 180 per group) after matching. The rates of ORR (70.56% vs. 47.22%), pCR (20.56% vs. 6.67%), and MPR (36.67% vs. 11.67%) in the Treatment group were statistically higher than those in the Control group (all P < 0.001). RFS and OS were prolonged with neoadjuvant PD-1 inhibitor plus chemotherapy at 1, 1.5, and 2 years (RFS HR = 0.330, 0.263, 0.302; OS HR = 0.363, 0.305, 0.358) with comparable perioperative safety. CPS showed limited discrimination. In contrast, dMMR and low NLR individually associated with deeper pathological response and longer survival. Neoadjuvant PD-1 inhibitor plus chemotherapy enhances tumor regression, facilitates downstaging, and confers early survival benefits with acceptable safety.