Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery in colorectal carcinoma at high risk of peritoneal carcinomatosis: short-term and long-term outcomes from the CHECK study – protocol for a randomised, multicentre, phase 3 trial

Abstract

IntroductionUp to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts’ involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking.Methods and analysisThis is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method.Ethics and disseminationThis trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings.Trial registration numberNCT03914820.

Adjuvant Hyperthermic Intraperitoneal Chemotherapy in Patients With Locally Advanced Colon Cancer (COLOPEC): 5-Year Results of a Randomized Multicenter Trial

“…11 Recently, a new trial protocol (the CHECK study) was published, which will determine the effect of adjuvant HIPEC with mitomycin-C and CO2 agitation. 8 But just like the French PROPHYLOCHIP trial that investigated second-look surgery plus HIPEC versus surveillance in patients at high risk of developing colorectal PM, this trial also includes patients with resected synchronous peritoneal or ovarian metastases. 12 In our opinion, therapy in such patients should no longer be regarded as prophylactic but rather as therapeutic for proven macroscopic PM.…”

“…Worldwide, adjuvant HIPEC using different protocols for different indications is still used in trial setting, and in some institutes even as part of daily clinical practice. [7][8][9] So far, to our knowledge, no long-term survival data from randomized trials on adjuvant HIPEC in colon ACCOMPANYING CONTENT cancer have been published. Therefore, this study aimed to determine long-term recurrence and survival outcomes and quality of life (QoL) after the last included patient of the COLOPEC trial had reached 5-year follow-up.…”