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Pathologic response and safety of preoperative treatment regimens in gastric cancer undergoing D2 gastrectomy: a real-world cohort study

Year: 2026

Type: article

Abstract: Objective: To compare pathological response and safety among three preoperative treatment regimens-chemotherapy alone, chemotherapy plus immunotherapy, and chemotherapy plus immunotherapy and targeted therapy-in gastric cancer undergoing D2 gastrectomy, and to assess biomarker associations with response. Methods: We retrospectively included 195 patients who received preoperative systemic therapy followed by D2 gastrectomy: chemotherapy alone (n = 47), chemotherapy plus immunotherapy (n = 100), or chemotherapy plus immunotherapy and targeted therapy (n = 48). Preoperative therapy was considered neoadjuvant for cM0 disease and conversion therapy for selected baseline cM1 disease. The primary endpoint was MPR (including pCR). pCR was also reported separately as a subset of MPR; secondary endpoints were preoperative treatment-related adverse events, surgical and pathological outcomes, and disease-free and overall survival (DFS, OS). Logistic regression was used to identify factors associated with MPR; DFS and OS were evaluated with Kaplan-Meier and Cox models. Results: Overall pCR and MPR rates were 20.5% and 40.0%. MPR rates were 27.7%, 37.0%, and 58.3% in the chemotherapy, chemotherapy+immunotherapy, and triple-regimen groups. The triple regimen improved MPR versus chemotherapy in unadjusted analysis, but regimen type was not an independent predictor after adjustment. Lauren intestinal subtype and PD-L1 CPS ≥5 were strongly associated with higher MPR, and in PD-L1-low tumors the triple regimen was associated with higher MPR. Rates of grade ≥3 adverse events and postoperative complications were similar across groups. DFS and OS did not differ significantly; higher cN stage and older age were associated with worse outcomes. Conclusion: Preoperative treatment regimens containing immunotherapy, particularly the triple combination, improved pathological response without increasing preoperative risk. Tumor biology-especially Lauren subtype and PD-L1 expression-had a greater impact on response than regimen intensity, supporting biomarker-guided strategies.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1766793