Emerging Role of Immunotherapy in Neoadjuvant, Adjuvant, and Perioperative Management of Gastric Cancer

Gastric cancer remains a major global cause of cancer mortality despite improvements in surgery, perioperative chemotherapy, radiotherapy, and supportive care. For resectable locally advanced gastric and gastroesophageal junction adenocarcinoma, perioperative chemotherapy with fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) has become a major standard of care; however, recurrence remains frequent, reflecting the persistence of micrometastatic disease and biological resistance. Immune checkpoint inhibitors have transformed the management of advanced gastric cancer and are now being investigated in curative-intent settings. The rationale for earlier use is strong: intact tumor antigen, preserved lymphatic priming, and potential eradication of micrometastases may enhance immune-mediated control. This review discusses the emerging role of immunotherapy in neoadjuvant, adjuvant, and perioperative gastric cancer management, with a particular focus on pivotal trials including DANTE, Neoadjuvant Nivolumab Plus Ipilimumab and Adjuvant Nivolumab (NEONIPIGA), KEYNOTE-585, ATTRACTION-5, CheckMate-577, and MATTERHORN. MATTERHORN represents the most important recent phase III advance, showing that perioperative durvalumab plus FLOT significantly improves event-free survival compared with FLOT alone in resectable gastric or gastroesophageal junction adenocarcinoma. Future integration of immunotherapy will require careful biomarker selection, interpretation of survival endpoints, toxicity management, and adaptation to regional treatment standards.