August’s paper of the month looks at the PRODIGE-7 trial, a multicentre randomised open-label, phase 3 trial which sought to determine whether hyperthermic intraperitoneal chemotherapy in patients undergoing cytoreductive surgery for colorectal peritoneal metastases
François Quénet, Dominique Elias, Lise Roca, Diane Goéré, Laurent Ghouti, Marc Pocard, Olivier Facy, Catherine Arvieux, Gérard Lorimier, Denis Pezet, Frédéric Marchal, Valeria Loi, Pierre Meeus, Beata Juzyna, Hélène de Forges, Jacques Paineau, Olivier Glehen, UNICANCER-GI Group and BIG Renape Group
The Lancet Oncol, Volume 22, issue 2, February 2021
What is known about the subject?
Peritoneal metastases are seen around one tenth of colorectal cancer patients and are associated with worse survival than extraperitoneal metastases. The combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) has been used for more than a decade for selected colorectal cancer patients with peritoneal metastases. However, the specific benefits
associated with adding HIPEC to cytoreductive surgery
have not been assessed in prospective trials.
What the study adds?
This is the first study to address the specific role of HIPEC when used in combination with cytoreductive surgery to treat peritoneal metastases secondary to colorectal cancer. 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). Grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035) within postoperative 2 months. The addition of oxaliplatin-based HIPEC to cytoreductive surgery did not significantly affect overall survival or relapse free survival compared with cytoreductive surgery alone, but was associated with a higher number of postoperative complications at 60 days. The curative management of peritoneal metastases secondary to colorectal cancer with cytoreductive surgery alone (in association with systemic chemotherapy) at specialised cancer centres was unexpectedly efficacious in terms of long-term recurrence-free survival.
Implications for colorectal practice
High-dose oxaliplatin-based HIPEC given over a short duration should no longer be used, and macroscopically complete cytoreductive surgery should be considered the mainstay of
treatment of peritoneal metastases. Eligibility for surgical resection should be the main consideration in patients with colorectal cancer and peritoneal metastases. Such changes to
clinical practice would spare patients with colorectal cancer from undergoing unnecessary intraperitoneal chemotherapy.