Study protocol for hyperthermic intraperitoneal chemotherapy in the treatment of locally advanced gastric cancer after laparoscopic or robotic Gastrectomy with D2 lymphadenectomy: a phase III multicentre prospective randomized controlled clinical trial (HIPEC-09).

BACKGROUND: Although some prospective clinical studies have shown comparable oncological outcomes between laparoscopic and open surgery for advanced gastric cancer, the 3-year recurrence-free survival rate of patients who undergo laparoscopic radical gastrectomy is lower than that of patients who undergo open radical gastrectomy. Animal experiments have also shown that laparoscopic surgery may increase the risk of peritoneal metastasis during carbon dioxide pneumoperitoneum. Previous single-centre clinical trials have confirmed that HIPEC can effectively eliminate free cancer cells, thereby improving the survival rate of patients with advanced gastric cancer. In this study, we aimed to investigate the safety and efficacy of the combination of laparoscopic gastrectomy with HIPEC in advanced gastric cancer to reduce the incidence of peritoneal metastasis. METHODS: A total of 616 patients will be randomly divided into 2 groups at a 1:1 ratio using central randomization after laparoscopic exploration in this prospective, randomized, controlled, open, multicentre clinical trial. The experimental arm will receive laparoscopic or robotic D2 surgery with 2 cycles of HIPEC treatment followed by 6–8 cycles of adjuvant chemotherapy, whereas the control group will undergo laparoscopic or robotic D2 surgery followed by 6–8 cycles of systemic chemotherapy. The primary endpoint for this study is 5-year recurrence-free survival. The secondary endpoints are the 5-year overall survival rate, peritoneal metastasis rate, peritoneal metastasis-free survival, regional recurrence rate, distant metastasis rate, toxicity and side effects of the treatment program. DISCUSSION: This is the first multicentre randomized controlled clinical study exploring whether HIPEC can prevent peritoneal metastasis after laparoscopic or robotic radical gastrectomy under carbon dioxide pneumoperitoneum for advanced gastric cancer. Minimally invasive surgery under carbon dioxide pneumoperitoneum can cause tremendous changes in the peritoneal microenvironment, increasing the risk of gastric cancer cell peritoneal dissemination and metastasis. In previous studies, the roles of HIPEC and laparoscopic gastrectomy for advanced gastric cancer have been confirmed. The innovation of this study lies in observing whether the combination of HIPEC can decrease the risk of peritoneal metastasis and recurrence in patients with advanced gastric cancer after laparoscopic or robotic gastrectomy under carbon dioxide pneumoperitoneum. TRIAL REGISTRATION: The trial was registered on 14/05/2023 under clinicaltrials.gov (Identifier: NCT05871099).