Perioperative Chemoimmunotherapy for Resectable Gastric and Gastroesophageal Junction Cancer: A Conceptual, Biomarker-Informed, and Regionally Adapted Framework.

Perioperative treatment for resectable gastric and gastroesophageal junction (GEJ) adenocarcinoma is changing rapidly as immune checkpoint inhibition enters a field historically shaped by distinct chemotherapy and surgical paradigms. This review critically appraises contemporary perioperative and adjuvant evidence and proposes a biomarker-informed, regionally adaptable framework for clinical decision-making. We conducted a structured narrative review of perioperative and adjuvant systemic therapy, surgical outcomes, treatment completion, safety, and biomarker evidence in resectable gastric and GEJ adenocarcinoma, with emphasis on randomized phase III trials, mature follow-up, prospective biomarker studies, and relevant regulatory data. MATTERHORN demonstrated significant event-free survival and subsequently overall survival benefits with perioperative durvalumab plus fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT), supporting regulatory approvals. In contrast, KEYNOTE-585 increased pathological complete response but did not meet the prespecified event-free survival statistical boundary, while ATTRACTION-5 did not establish postoperative nivolumab after D2 gastrectomy as a new standard. MSI-H/dMMR is the most clinically relevant perioperative biomarker, although chemotherapy-free strategies remain investigational. PD-L1 thresholds validated in advanced disease should not be directly transferred to the curative setting. Pathological response, ypN status, circulating tumor DNA/molecular residual disease, and emerging multimodal risk models are prognostic, but none currently provides validated treatment-effect prediction sufficient to mandate postoperative escalation or de-escalation. Perioperative treatment should integrate resectability, surgical quality, patient fitness, regional chemotherapy backbones, MSI-H/dMMR status, treatment completion, and postoperative recovery. The proposed framework is conceptual rather than a guideline and requires prospective validation.