Advancing gastric cancer treatment: A comprehensive review of hyperthermic intraperitoneal chemotherapy's role and outcomes.

Background: Peritoneal metastases (PM) represent the most frequent and lethal form of dissemination in advanced gastric cancer (GC), with limited efficacy of systemic chemotherapy [median overall survival (OS): 2-9 months]. Over the past decades, hyperthermic intraperitoneal chemotherapy (HIPEC), often combined with cytoreductive surgery (CRS), has emerged as a locoregional strategy to improve peritoneal disease control. Retrospective studies have suggested promising survival benefits (median OS: 18.8 months); however, conflicting results from prospective trials have limited its widespread adoption. This systematic review hypothesizes that selected patients with advanced or high-risk GC may benefit from HIPEC and evaluates whether such benefits have been confirmed in recent prospective evidence.

Aim: To evaluate the role and outcomes of HIPEC in advanced and high-risk GC through a systematic review of prospective trials.

Methods: A systematic review of prospective randomized and controlled clinical trials (2010-2024) was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Studies were selected from PubMed, Cochrane, Scopus, and ClinicalTrials.gov. No geographical restrictions were applied in the search process. Eligible studies included patients with advanced GC (T3+, positive peritoneal cytology/PM) receiving HIPEC in either therapeutic or prophylactic settings. Exclusion criteria included retrospective studies, single-arm trials, and those lacking survival outcomes. Risk of bias was assessed using Risk of Bias 2.0 and Risk of Bias in Non-Randomized Studies of Interventions tools; sensitivity and heterogeneity analyses were also conducted.

Results: Thirteen prospective studies (eight therapeutic, five prophylactic) were included. In therapeutic settings, CRS combined with HIPEC yielded a median OS of 11-24.9 months vs 4-6 months with systemic therapy alone. Completeness of cytoreduction (CC-0) was achieved in 67.3% of cases, and associated with improved disease-free survival. In prophylactic settings, HIPEC significantly reduced peritoneal recurrence, particularly in T4 tumors. Sensitivity analyses confirmed robustness of findings, though benefit was driven by a few key trials. Heterogeneity was moderate across studies; lack of standardized HIPEC protocols and patient selection criteria limited comparability.

Conclusion: HIPEC may improve survival and reduce recurrence in selected GC patients, particularly those with low peritoneal burden and CC-0 resection. Further standardization and prospective trials are needed.