Hyperthermic intraperitoneal chemotherapy for management of gastrointestinal and biliary tract malignancies: a systematic review and meta-analysis of randomized trials

Abstract

Background: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) promised to transform the management of peritoneal carcinomatosis (PC). Forty years since the introduction of the technique, published data from randomized controlled trials (RCTs) remain scarce. We assessed the cumulative comprehensive available evidence on the use of HIPEC in gastrointestinal (GI) and biliary tract malignancies and established the current benchmark for GI HIPEC research in both the prevention and treatment of peritoneal metastases. Methods: RCTs were identified through a systematic search of Medline, Cochrane and Embase databases. Overall survival and progression-free survival were the outcomes of interest. Results: The search resulted in 13 RCTs for gastric cancer (10 on prophylactic and 3 on therapeutic HIPEC), 4 for colorectal cancer (2 on prophylactic and 2 on therapeutic HIPEC), and 1 for pancreatic cancer. No RCTs were identified that included other types of GI or biliary tract cancers. Current randomized evidence does not support any overall survival benefit from the use of HIPEC in the adjuvant setting for gastric cancer or for colorectal cancer in any setting. Despite the survival benefit noticed in the treatment of PC from gastric cancer (risk ratio 0.85, 95% confidence interval 0.77-0.93; P<0.001), the results were derived from only 190 patients. Conclusions: The current evidence from RCTs does not support the use of HIPEC in the treatment/prevention of PC in GI and biliary tract malignancies. HIPEC should continue to be considered experimental until level 1 evidence from properly designed international multicenter studies becomes available.