Chemotherapy Options for Locally Advanced Gastric Cancer: A Review

Gastric cancer ranks as the sixth most common cancer globally and remains a significant contributor to cancer-related mortality. Detection at the stage of locally advanced gastric cancer (LAGC) offers an opportunity to improve survival outcomes through a multimodal treatment approach. Current management typically involves a combination of neoadjuvant and adjuvant systemic chemotherapy alongside gastrectomy. In select cases, the strategy is expanded to include targeted therapy and intraperitoneal chemotherapy (IPC), delivered via hyperthermic intraperitoneal chemotherapy (HIPEC) or pressurized intraperitoneal aerosol chemotherapy (PIPAC). While systemic chemotherapy and targeted therapies are implemented both preoperatively and postoperatively, IPC is often utilized postoperatively but can also be administered preoperatively or intraoperatively. Targeted therapy remains an area of active investigation in the LAGC setting, with promising agents targeting pathways such as HER2 and VEGF. However, the role of IPC modalities is less well established. The clinical utility of HIPEC remains controversial due to mixed outcomes in trials, and there is a paucity of clinical studies evaluating the preventive role of PIPAC. Future research is needed to elucidate the potential of novel targeted therapies and IPC modalities in the treatment of LAGC, particularly concerning optimal timing, frequency, and integration with systemic therapies. This review aims to summarize the current state of knowledge on chemotherapy options for LAGC, highlight existing gaps and controversies, and propose directions for future research.