Hyperthermic Intraperitoneal Chemotherapy in Gastric Cancer: Distinguishing Prophylactic and Therapeutic Roles Within Contemporary Multimodal Management

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Peritoneal metastasis (PM) remains one of the most clinically important determinants of poor outcome in gastric cancer (GC), given the limited efficacy of systemic therapy within the peritoneal compartment. This has driven sustained interest in hyperthermic intraperitoneal chemotherapy (HIPEC), administered after cytoreductive surgery (CRS), as a strategy to improve locoregional disease control, although its role remains controversial in both prophylactic and therapeutic settings. A narrative review of the literature was performed using published randomized controlled trials, prospective cohort studies, retrospective comparative analyses, systematic reviews, and meta-analyses evaluating HIPEC in GC. Particular emphasis was placed on biological rationale, patient selection, disease burden, completeness of cytoreduction, treatment protocols, perioperative morbidity, and oncologic outcomes. The prophylactic and therapeutic applications of HIPEC were evaluated separately to avoid conflating two biologically and clinically distinct questions. In high-risk resectable disease, prophylactic HIPEC demonstrates a recurrent signal toward reduced peritoneal recurrence and improved disease-free survival, although supporting evidence remains heterogeneous and largely nonrandomized. In established PM, earlier studies and selected retrospective analyses suggested a survival signal with CRS-HIPEC; however, contemporary randomized trials, particularly GASTRIPEC-I and PERISCOPE II, have not demonstrated a convincing overall survival benefit and have highlighted important concerns regarding treatment-related morbidity and clinical trade-offs. Across both settings, outcomes appear highly dependent on patient selection, especially peritoneal cancer index, tumor biology, and the feasibility of complete cytoreduction. Overall, HIPEC remains biologically compelling but clinically unconfirmed as routine care in GC. At present, prophylactic HIPEC should be regarded as investigational but promising, whereas therapeutic CRS-HIPEC for established gastric PM should remain restricted to highly selected patients managed in experienced centers and, ideally, within clinical trials or prospective registries.