Comment on Moran’s “Light at the End of the Tunnel”: The Pulmonary Metastasectomy in Colorectal Cancer Study Sheds Some Light on the Question

Abstract

To the Editor-The editorial about resection of colorectal cancer peritoneal metastases referred to the pulmonary metastasectomy in colorectal cancer (PulMiCC) randomized controlled trial (RCT) 1 only to dismiss it. 2 We write to update the citation 3 and summarize some published data from the full PulMiCC study. 4,5 Recruitment reached 512 patients, but the Society of Thoracic Surgeons published consensus, that without metastasectomy survival would be zero 6 , led to the majority of patients (N = 263) being selected for metastasectomy. 4 The 22% 5-year survival among 128 unoperated patients refutes the zero assumption (p < 0.001). 4 All prognostic factors favored the operated patients: fewer (31% vs 65%) had solitary metastases, elevated carcinoembryonic antigen, liver involvement, and impaired performance status. They were younger with better lung function. Fiveyear survival (~60%) was comparable with the best of "real world" outcomes. 7 For the patients who were randomly assigned, prognostic factors were excellently balanced in the 2 arms of the nested RCT. There was no survival difference at any time point. 3 The number randomized (N = 93) precluded proof of noninferiority, but the generally believed large benefit can be confidently refuted. 8 Moran cited median survival of 42 months in PRODIGE as evidence for effectiveness of peritoneal resection, but it was hyperthermic intraperitoneal chemotherapy that was under test. There were no unoperated patients. 9 Without well-balanced controls, there is no proof of benefit. Similar median survival values were seen in the PulMiCC RCT, that is, 42 months for treated group and 45.6 months for control. 9 Selection for inclusion and guarantee time bias play a major part in the much better than expected survival rates. 5,10