Efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy for locally advanced colorectal cancer (HIPECT4): final analysis of randomized clinical trial

Abstract

BACKGROUND: Despite adjuvant systemic chemotherapy after surgical resection in patients with pT4 stage colon cancer, a high percentage of them will develop peritoneal metastases. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) is a treatment option with the goal of preventing metachronous peritoneal metastases. The aim of this study was to report the longer-term outcomes of peritoneal control with the use of intraoperative HIPEC based on mitomycin C after the last enrolled patient of the HIPECT4 trial reached 36 months follow-up. METHODS: Between November 2015 and March 2021, patients with resectable primary clinical T4 N0-2M0 were included and randomized (1:1) to either adjuvant HIPEC with mitomycin C (30 mg/m2, 60 minutes) or standard treatment. The primary endpoint was locoregional control at 36 months. Kaplan-Meier survival analysis with a log-rank test was used to compare the two study groups. RESULTS: A total of 184 patients were included and followed up at 36 months. The locoregional control rate was improved with HIPEC compared with adjuvant chemotherapy alone (hazard ratio 0.19, 95% confidence interval 0.04 to 0.86; P = 0.031). Three years overall survival and disease-free survival did not differ between patients assigned to the HIPEC and control groups. Subgroup analysis showed better locoregional control with the use of HIPEC for patients with definitive pT4 colon cancer (hazard ratio 0.08, 0.01 to 0.65; P = 0.017) and per protocol (receiving adjuvant chemotherapy) patients (hazard ratio 0.18, 0.04 to 0.83; P = 0.028). The pattern of recurrence was modified significantly using HIPEC with less peritoneal relapse. CONCLUSION: The long-term outcome analysis of the HIPECT4 trial demonstrated that using mitomycin C-based HIPEC reduced peritoneal recurrence in patients with locally advanced colon cancer without increasing toxicity. However, there was no difference in overall survival and disease-free survival. REGISTRATION NUMBER: NCT02614534 (https://clinicaltrials.gov/).