Hyperthermic Intraperitoneal Chemotherapy Plus Cytoreductive Surgery for Colorectal Cancer Metastases Does Not Improve Overall Survival

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As reported in The Lancet Oncology by Quénet et al, the French phase III PRODIGE 7 trial has shown that the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery did not improve overall survival—and was associated with an increase in postoperative late complications—in patients with colorectal peritoneal metastases.

Study Details

The multicenter open-label trial included 265 patients with complete macroscopic resection or surgical resection with < 1 mm residual tumor tissue. They were randomly assigned perioperatively between February 2008 and January 2014 to receive oxaliplatin-based HIPEC plus cytoreductive surgery (n = 133) or surgery alone (n = 132).

Oxaliplatin HIPEC was administered via closed (360 mg/m²) or open (460 mg/m²) abdomen techniques, with systemic chemotherapy with fluorouracil at 400 mg/m² and leucovorin at 20 mg/m² given intravenously 20 minutes before HIPEC. All patients received investigator’s choice of systemic chemotherapy with or without targeted therapy before and/or after surgery.

The primary endpoint was overall survival in the intention-to-treat population.

Overall Survival

Peritoneal metastases were completely resected in 119 (89%) of 133 patients in the HIPEC group and in 121 (92%) of 132 patients in the surgery-alone group. Median follow-up was 63.8 months (interquartile range [IQR] = 53.0­–77.1 months). Median overall survival was 41.7 months (95% confidence interval [CI] = 36.2–53.8 months) in the HIPEC group vs 41.2 months (95% CI = 35.1–49.7 months) in the surgery-alone group (hazard ratio [HR] = 1.00, 95.37% CI = 0.63–1.58, P = .99). No significant differences in survival were observed in subgroup analyses. Overall survival at 1 and 5 years was 86.9% vs 88.3% and 39.4% vs 36.7%.

Median relapse-free survival was 13.1 months vs 11.1 months (HR = 0.91, P = .43). Rates at 1 and 5 years were 59.0% vs 46.1% and 14.8% vs 13.1%. Peritoneal-free survival did not significantly differ between groups; the rates of multiple metastatic occurrences were 29% vs 31%.

Adverse Events

Grade ≥ 3 adverse events at 30 days were observed in 42% of patients in the HIPEC group vs 32% of the surgery-alone group (P = .083). The most common intra-abdominal complications were digestive fistulae (11% vs 7%) and abscesses (5% vs 3%).

Treatment-related deaths occurred at 30 days in two patients (2%) in each group, with causes consisting of cardiac failure and massive pneumonia in the HIPEC group and intraperitoneal hemorrhage and septic shock in the surgery-alone group. Grade ≥ 3 adverse events at 60 days were observed in 26% of patients (including 27 of 34 with an event at day 30) in the HIPEC group vs 15% of patients (including 14 of 20 with an event at day 30) in the surgery-alone group (P = .035). Additional treatment-related deaths at 60 days occurred in two patients (2%) in the HIPEC group, with causes consisting of pulmonary embolism and bilateral pneumonia, and in one patient (1%) in the surgery-alone group, due to acute respiratory distress.

The investigators concluded, “Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases.”

François Quénet, MD, of the Department of Surgical Oncology, L’Institut du Cancer de Montpellier, is the corresponding author for The Lancet Oncology article.

Disclosure: The study was funded by Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, and Ligue Contre le Cancer. For full disclosures of the study authors, visit