Neoadjuvant Chemotherapy for Gastric Cancer: Evolving Approaches and Supporting Evidence

Neoadjuvant and perioperative therapy have emerged as promising strategies for managing locally advanced gastric cancer (LAGC). Landmark phase III studies, such as PRODIGY and RESOLVE, have established neoadjuvant chemotherapy as a viable therapeutic option in Asia. More recently, the MATTERHORN trial demonstrated the potential of incorporating immune checkpoint inhibitors (ICIs) into perioperative treatment. However, the use of fluorouracil, leucovorin, oxaliplatin, and docetaxel in Asian populations warrants careful consideration, given regional treatment standards and concerns regarding chemotherapy-related toxicities, including neutropenia. This review summarizes key perioperative trials and highlights the evolving role of ICIs while also addressing emerging evidence on targeted therapies in LAGC. Key considerations include assessment of treatment response, as the validity of pathological response as a surrogate endpoint for survival remains unclear; risk- and biomarker-driven patient selection; and unresolved questions regarding the necessity and optimal duration of postoperative therapy. Personalizing postoperative treatment based on prognostic and molecular markers-including clinical stage, pathological response, and circulating tumor DNA status-represents an important next step toward improving outcomes.