Perioperative PD-1 inhibitor plus chemotherapy versus chemotherapy alone in gastric cancer with PAN metastasis undergoing D2 gastrectomy and PAND: a single-center retrospective cohort study.

OBJECTIVES: Research on the efficacy of perioperative immunotherapy for gastric cancer with para-aortic lymph node (PAN) metastasis remains limited. This study aimed to compare the safety and efficacy of chemotherapy plus programmed cell death protein-1 (PD-1) inhibitor versus chemotherapy alone in locally advanced GC patients with PAN metastasis. METHODS: We retrospectively reviewed patients with gastric cancer and limited No.16a2/b1 lymph node metastasis who received perioperative systemic therapy combined with D2 gastrectomy plus PAN dissection (PAND) between January 2018 and February 2024. Patients were divided into Group A (chemotherapy+PD-1 inhibitor, n=62) and Group B (chemotherapy alone, n=71). Pathological response, survival outcomes, and safety were evaluated. RESULTS: All patients in Group A achieved R0 resection, compared with 98.6% in Group B. Pathological outcomes were significantly better in Group A, with higher rates of pathological complete response (pCR; 37.1% vs. 4.2%, P<0.001) and major pathological response (MPR; 58.1% vs. 22.5%, P<0.001) compared to Group B. In Group A, patients with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥5 had higher pCR rates. The 3-year overall survival (OS) rate was also higher in Group A (64.5% vs. 42.3%). The median OS for Group B was 33.2 months, while Group A was not reached (P = 0.023). Adverse event incidences were comparable between groups, with no treatment-related deaths. CONCLUSION: Perioperative immunochemotherapy significantly enhances pathological response and survival in GC patients with PAN metastasis, with manageable safety. This regimen represents a promising therapeutic strategy for this patient population, necessitating long-term follow-up to confirm durable benefits.