Limitations of the PRODIGE 7 trial.

Abstract

We read with great interest the full results of the PRODIGE 7 trial by François Quénet and colleagues. 1 Quénet F Elias D Roca L et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22: 256-266 Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar The authors concluded that the addition of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery is not advisable in patients with colorectal peritoneal metastases. We must congratulate the authors for their outstanding experience in this field and on the results of the study. The preliminary results of the PRODIGE 7 trial have been widely criticised because of several technical and methodological weaknesses, particularly with regards to the dose and method of oxaliplatin delivery. 2 Celeen W HIPEC with oxaliplatin for colorectal peritoneal metastasis: the end of the road. Eur J Surg Oncol. 2019; 45: 400-402 Summary Full Text Full Text PDF PubMed Scopus (52) Google Scholar , 3 Liberale G PRODIGE 7 should be interpreted with caution. Acta Chir Belg. 2019; 119: 263-266 Crossref PubMed Scopus (7) Google Scholar We would like to point out some additional factors that might have affected the final results of this study. 1 Quénet F Elias D Roca L et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22: 256-266 Summary Full Text Full Text PDF PubMed Scopus (74) Google Scholar Limitations of the PRODIGE 7 trialThe authors of the long-awaited PRODIGE 7 trial1 are to be congratulated for completing the first randomised trial assessing the value of oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) after complete or near-complete cytoreductive surgery for colorectal peritoneal metastases. Although the authors addressed the trial's limitations regarding the sample size calculation and the choice of high-dose, short-duration oxaliplatin given as a single intraperitoneal dose, important issues about the trial's external validity received relatively less attention. Full-Text PDF Limitations of the PRODIGE 7 trialThe authors of the PRODIGE 7 trial1 should be congratulated for conceiving and completing this trial at a time when no other study has evaluated the role of cytoreductive surgery alone for the treatment of colorectal peritoneal metastases. No benefit in the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery was observed, but the unprecedented median overall survival of more than 40 months in both groups (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) establishes the role of cytoreductive surgery in this setting. Full-Text PDF Limitations of the PRODIGE 7 trialThe PRODIGE 7 trial1 showed the key role of cytoreductive surgery in the treatment of patients with colorectal peritoneal metastases, but did not show a survival benefit for oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC). However, these results contradict those of a large randomised controlled trial comparing surgery alone with cytoreductive surgery plus HIPEC in patients with ovarian cancer.2 An unmistakable 1-year survival benefit was shown for cytoreductive surgery plus HIPEC in this trial,2 which is an effect that is seldomly achieved by oncological drugs in randomised controlled trials. Full-Text PDF Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trialConsidering 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. Full-Text PDF Limitations of the PRODIGE 7 trialI would like to congratulate the authors of the recent PRODIGE 7 trial1 for their important contribution to hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with colorectal peritoneal metastases. The relevant question of the added benefit of HIPEC to cytoreductive surgery has never been evaluated in a randomised trial. It is an important research topic and clinical question. Several randomised trials and well done propensity score-matched comparisons have provided proof of concept of adding HIPEC to cytoreductive surgery for treating peritoneal surface malignancy. Full-Text PDF Limitations of the PRODIGE 7 trial – Authors' replyWe thank Aditi Bhatt and colleagues, Fabio Carboni and Mario Valle, Michael A Ströhlein and Markus M Heiss, Peter Cashin, and Koen P Rovers and colleagues for their interest in the PRODIGE 7 trial.1 Full-Text PDF