HIPEC addition to complete surgical resection beneficial for patients with locally advanced colon cancer: JAMA

The phase 3 randomized clinical trial of 184 adults in Spain revealed an improvement in the locoregional control rate at three years in the HIPEC group (97%) versus the surgery alone group (87%), without an increase in morbidity. Patients in the HIPEC group received cytoreduction plus HIPEC with mitomycin C and patients in the other group (comparator group) received cytoreduction alone.

Advances in colon cancer treatment continue to change the disease course and improve patients' lives and survival. Locally advanced colon cancer, T4 or perforated, is a problematic scenario linked with poor outcomes. Adjuvant chemotherapy is often recommended, but limited evidence supports its use in stage II pT4 colon cancer. Despite adequate surgical and systemic treatment, peritoneal metastasis in locally advanced colon cancer (T4 stage) patients can recur as high as 25% at three years from surgical resection and is tied to poor prognosis. The clinical benefit of prophylactic HIPEC is controversial in these patients.

Against the above background, Alvaro Arjona-Sánchez, University Hospital Reina Sofia, Córdoba, Spain, and colleagues aimed to assess the safety and efficacy of intraoperative HIPEC in patients with locally advanced colon cancer in an open-label, phase 3 randomized clinical trial. They determined if using hyperthermic intraperitoneal chemotherapy with mitomycin C and complete cytoreduction improves locoregional control in these patients.

The trial was conducted at 17 Spanish centres and enrolled patients aged 18 to 75 with locally advanced primary colon cancer diagnosed preoperatively. One hundred eighty-four patients were randomly allocated in a ratio of 1:1 to the investigational group (n=89) or comparator group (n=95). Those in the investigational group received cytoreduction and HIPEC with mitomycin C (30 mg/m2 over 60 minutes), and those in the comparator group received cytoreduction alone. Both were followed by systemic adjuvant chemotherapy. The mean age of the participants was 61.5 years, and 60.3% were male. They were followed for a median of 36 months.

The three-year locoregional control (LC) rate (primary outcome) was defined as the percentage of patients without the recurrence of peritoneal disease analyzed by intention to treat. Secondary endpoints included overall survival, disease-free survival, rate of toxic effects, and morbidity.

The study revealed the following findings:

• Demographic and clinical characteristics were found to be similar between groups.
• In the investigational group, the 3-year LC rate was higher (97.6%) than in the comparator group (87.6%) (hazard ratio [HR], 0.21).
• No differences were found in the groups for disease-free survival (investigational, 81.2%; comparator, 78.0%; HR, 0.71) or overall survival (investigational, 91.7%; comparator, 92.9%; HR, 0.79).
• The definitive subgroup with pT4 disease revealed a pronounced benefit in the 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; HR, 0.09).
• No differences in toxic effects or morbidity between groups were observed.

Based on the findings, the researchers suggest considering hyperthermic intraperitoneal chemotherapy for locally advanced colorectal cancer patients.

Reference:

Arjona-Sánchez A, Espinosa-Redondo E, Gutiérrez-Calvo A, et al. Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial. JAMA Surg. Published online April 26, 2023. doi:10.1001/jamasurg.2023.0662