Peritoneal metastasis in locally advanced colon cancer (T4 stage) is estimated around 25% at 3 years from surgical resection with a poor prognosis. There is controversy about the results using prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in this group of patients. We led a randomized controlled trial to determine the efficacy and safety of adjuvant HIPEC in patients with locally advanced colon cancer.
We did an open-label, randomized phase III study in 17 hospitals in Spain. Eligible patients were aged 18-75 years and had locally advanced primary colorectal cancer diagnosed preoperatively (cT4NxM0). Patients were randomly assigned (1:1) to surgery or surgery plus HIPEC (mitomycin C 30 mg/m2 during 60 minutes), both followed by systemic adjuvant chemotherapy. Randomisation was done via a web-based system, with stratification by treatment centre and gender. The primary outcome was 3 years loco-regional control rate, defined as the time from treatment to peritoneal disease recurrence or death form any cause, analysed by intention to treat (ITT). DFS and OS were secondary endpoints.
Between November 2015 and January 2021 184 patients were recruited and randomized (89 experimental vs. 95 control). The median of follow-up was 36 (IQR 27-36) months. Demographic, tumour features, surgical management and final pathology reports were similar between both groups. The loco-regional control (LC) was improved in the experimental arm (35,3 ± 0.4 vs. 33.2 ± 0.8 months) with a 3 years LC rate of 97% vs. 87% (p = 0.025). No differences were observed in DFS and OS. The pT4 subgroup showed a clear benefit of LC in the HIPEC arm. No differences in morbidity were observed between groups.
The addition of hyperthermic intraperitoneal chemotherapy with mitomycin C to a complete surgical resection for locally advanced colon cancer improves the loco-regional control rate. This benefit becomes more evident in the subgroup of patients with pT4 colon cancer.
Clinical trial identification
Legal entity responsible for the study
IMIBIC Maimonides Biomedical research Institute cordoba, Spain. Universitary Hospital Reina Sofia, Cordoba, Spain.
FIBICO (Biomedical Research Foundation, Cordoba) and Spanish Surgeon's Association (AEC).
All authors have declared no conflicts of interest.