Less Is More: No Benefit Reported for Hyperthermic Intraperitoneal Chemotherapy in Colorectal Cancer

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With a growing emphasis on value in cancer care, some types of resource-intensive therapies may need to be reconsidered. One such treatment may be hyperthermic intraperitoneal chemotherapy, which showed no benefit during surgery for colorectal cancer confined to the peritoneum in the PRODIGE 7 trial. Overall survival was not significantly different at 5 years in patients treated with this intensive chemotherapy than in those who were not: 41.7 months vs 41.2 months.1

François Quenet, MD

François Quenet, MD

“The addition of hyperthermic intraperitoneal chemotherapy with oxaliplatin does not influence the survival results. The survival rate of the surgery-alone group was unexpectedly high, which means that every colorectal cancer patient with isolated peritoneal carcinomatosis should be considered for surgery,” said lead author François Quenet, MD, of the Regional Cancer Institute, Montpelier, France.

In many developed countries, including the United States, hyperthermic intraperitoneal chemotherapy with oxaliplatin heated to 43°C in an attempt to increase the efficacy of chemotherapy during surgical removal of peritoneal carcinomatosis. Peritoneal carcinomatosis—tumors confined to the lining of the abdomen—occur in about 20% of cases of metastatic colorectal cancer.

“In the natural history of the disease, survival is less than 6 months. Today, when the patient is not able to be resected, the prognosis is 16 months of survival with modern systemic chemotherapy alone. If the patient is able to have complete resection of the tumors and hyperthermic intraperitoneal chemotherapy, the prognosis is 40 months of survival. In the best case, we can cure 16% of patients,” Dr. Quenet said.

“When this approach was introduced more than 15 years ago, it was the first effective treatment for metastatic tumors on a patient’s abdomen, but we didn’t know whether delivering heated chemotherapy during surgery was an important component of the treatment or not. This is the first randomized study assessing hyperthermic intraperitoneal chemotherapy in advanced colorectal cancer, and it shows no added benefit over surgery,” Dr. Quenet said.

Key Study Findings

The phaseIII PRODIGE 7 trial enrolled 265 patients at 17 centers in France; all patients had stage IV colorectal cancer and peritoneal carcinomatosis and no other metastatic sites. Patients were randomized 1:1 to undergo surgery (complete resection with at least 1-mm surgical margin) plus hyperthermic intraperitoneal chemotherapy or surgery alone. In both treatment arms, 96% of patients had been treated with systemic chemotherapy (physician’s choice) for 6 months before surgery, after surgery, or both.


  • No survival benefit was reported with hyperthermic intraperitoneal chemotherapy during surgery in patients with colorectal cancer and isolated peritoneal carcinomatosis.
  • This intensive chemotherapy was associated with more postoperative complications than surgery alone.
  • Hyperthermic intraperitoneal chemotherapy should not be used for routine treatment of peritoneal carcinomatosis outside of a clinical trial setting. 
  • For more information on the results of the PRODIGE 7 trial, see an interview with Michael J. Overman, MD, and François Quenet, MD, on The ASCO Post Newsreels at

At a median follow-up of 64 months, the median overall survival was 41.7 months in the hyperthermic intraperitoneal chemotherapy group vs 41.2 months in the non–hyperthermic intraperitoneal chemotherapy group. The 1-year survival rate was 86.9% and 88.3%, respectively, and the 5-year survival rate was 39.4% and 36.7%, respectively.

Recurrence-free survival was similar between the two groups: median of 13.1 months in the hyperthermic intraperitoneal chemotherapy group vs median of 11.1 months in the non–hyperthermic intraperitoneal chemotherapy group. One-year recurrence-free survival rates were 59% in the chemotherapy arm and 46.1% in the nonchemotherapy arm. The 5-year recurrence-free survival rates was 14.8% and 13.1%, respectively.

The overall mortality rate 30 days after surgery was 1.5% in both groups. There was no difference in the rate of adverse events in the first 30 days. By 60 days, the rate of grade 3 and 4 complications in the hyperthermic intraperitoneal chemotherapy group was almost double that in the nonchemotherapy group: 24.1% vs 13.6% (P = .030). Most complications were extra-abdominal.

Clinical Implications

A subgroup analysis suggested that hyperthermic intraperitoneal chemotherapy may be beneficial for patients with a medium disease burden in the peritoneal cavity, but this was not a pre-planned analysis and was based on small numbers of patients, so the findings are not conclusive. 

Dr. Quenet’s take-away message was that hyperthermic intraperitoneal chemotherapy is not necessary for patients with a low disease burden, nor is it necessary for patients with a high disease burden. But for those with a medium disease burden, more research is needed. 

DISCLOSURE: Dr. Quenet has received honoraria from Sanofi/Aventis, Novartis, and Ethicon; has been a consultant or advisor to Sanofi/Aventis, Ethicon, and Gamida Cell; and has received travel expenses from Sanofi, Novartis, and Ethicon.


1. Quenet F, Elias D, Roca L, et al: A UNICANCER phase III trial of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis: PRODIGE 7. 2018 ASCO Annual Meeting. Abstract LBA3503. Presented June 5, 2018.

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Expert Point of View: Andrew Epstein, MD

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“This is a very important study,” said ASCO expert Andrew Epstein, MD, of Memorial Sloan Kettering Cancer Center (MSK), New York. “Hyperthermic intraperitoneal chemotherapy is used in the United States and elsewhere, even though the benefits are unknown. This study shows...