Second-Look Surgery Plus HIPEC vs Surveillance for Patients at High Risk for Colorectal Peritoneal Metastases

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In a French phase III trial (PROPHYLOCHIP–PRODIGE 15) reported in The Lancet Oncology, Goéré et al found that second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) did not improve disease-free survival vs standard surveillance in patients at high risk of developing colorectal peritoneal metastases.

Study Details

The multicenter open-label trial included 150 patients with primary colorectal cancer and synchronous and localized colorectal peritoneal metastases removed during tumor resection, resected ovarian metastases, or a perforated tumor. Patients were randomly assigned between June 2010 and March 2015 to receive second-look surgery plus HIPEC (n = 75) or surveillance after resection of colorectal cancer according to French guidelines (n = 75) after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence.

Patients in the second-look surgery group received oxaliplatin/HIPEC (oxaliplatin at 460 mg/m², or oxaliplatin at 300 mg/m² plus irinotecan at 200 mg/m², plus fluorouracil at 400 mg/m²) or mitomycin/HIPEC (mitomycin at 35 mg/m²) alone in case of neuropathy. Second-look surgery consisted of complete exploration of the abdominal cavity via xyphopubic incision, with resection of all resectable peritoneal implants. The primary outcome was 3-year disease-free survival in the intention-to-treat population.


  • Second-look surgery plus HIPEC did not improve disease-free survival vs standard surveillance.
  • No differences in peritoneal recurrence-free survival or overall survival were observed.
  • Disease-Free Survival

    Median follow-up was 50.8 months. Second-look surgery was performed in 71 of the 75 patients in the second-look surgery group; of these, 67 received HIPEC, with 59 receiving oxaliplatin/HIPEC.

    Three-year disease-free survival was 53% in the surveillance group vs 44% in the second-look surgery group (hazard ratio = 0.97, 95% confidence interval = 0.61–1.56, P = .82). No significant difference was observed in 5-year disease-free survival (49% vs 42%, P = .82) or 3-year peritoneal recurrence-free survival (61% vs 59%). No differences were observed in 3-year overall survival (80% vs 79%) or 5-year overall survival (72% vs 68%).

    Adverse Events

    Grade 3 or 4 adverse events occurred in 41% of the second-look surgery group, with the most common being intra-abdominal adverse events (hemorrhage, digestive leakage; 23%) and hematologic adverse events (18%). No treatment-related deaths were reported.

    The investigators concluded, “Systematic second-look surgery plus oxaliplatin/HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes.”

    Diane Goéré, MD, of University Hospital Saint-Louis, Assistance Publique–Hôpitaux de Paris, is the corresponding author for The Lancet Oncology article.

    Disclosure: The study was funded by the French National Cancer Institute. For full disclosures of the study authors, visit