Hyperthermic intraperitoneal chemotherapy for gastric cancer: a narrative review

Abstract

Background and objective: Gastric cancer (GC) is the 5th most common malignancy globally, and although there have been modest gains in improving survival rates, it remains a leading cause of death. A component contributing to the poor survival rates includes advanced disease stage at presentation. Approximately 30-40% of GC patients present with metastases at diagnosis, with poorer outcomes when peritoneal metastases are present. However, recent studies have demonstrated potential utility of hyperthermic intraperitoneal chemotherapy (HIPEC) for GC with peritoneal carcinomatosis (GCPC) and for prevention of peritoneal carcinomatosis in high-risk patients. HIPEC for GC is highly debated. It is currently not recommended as part of standard of care for GC. The objective of this study is to discuss the various factors influencing the success of HIPEC, current intraperitoneal (IP) chemotherapy treatment regimens, timing of HIPEC administration, major randomized controlled trials (RCTs) and non-RCTs (NRCTs), and meta-analyses in GC patients.

Methods: A review of the Library of Congress, the Cochrane Review, Google Scholar, PubMed, and ClinicalTrials.gov was performed. All articles and trials with available data in English with full text were considered. Necessary keywords used to search included "gastric cancer" and/or "HIPEC". Included articles were independently reviewed by authors.

Key content and findings: Optimal HIPEC administration timing is unclear, but many utilize it in a neoadjuvant or prophylactic setting. Signet ring pathology and epithelial mesenchymal transition (EMT) cell histologic subtypes may have more aggressive pathology, limiting HIPEC success rates. Patients who receive complete cytoreduction and have low peritoneal carcinomatosis index (PCI) burden have been shown to have improved median overall survival (OS) after HIPEC. The data suggests in GCPC, HIPEC can modestly improve recurrence-free and OS. The data regarding benefits of prophylactic HIPEC in advanced GC (AGC) remains mixed.

Conclusions: HIPEC for GC is controversial. Much of the literature is exploratory in nature or difficult to compare, as many outcomes are novel/not cross validated against substantial preceding data, with highly variable patient populations and study designs. However, in certain clinical scenarios in high volume centers, some patients with non-metastatic or low burden disease who undergo prophylactic or intraoperative HIPEC may benefit with improved overall and recurrence free survival (RFS).

Keywords: Hyperthermic intraperitoneal chemotherapy (HIPEC); cytoreductive surgery (CRS); gastric cancer (GC); peritoneal carcinomatosis index (PCI); stage.