A history of lung metastasectomy may be told in narratives but we need randomized controlled trials to know what treatments should be used in the future

Abstract

© AME Surgical Journal. All rights reserved. AME Surg J 2021 | https://dx.doi.org/10.21037/asj-21-91 “Large randomized controlled trials are needed to guide our future management of colorectal lung metastases.” This is the final sentence of the narrative review by Ka Lun Mak and Michael Kuan Yew Hsin (1). We fully agree with them and we use that as our starting point, encouraging them and our many colleagues around the world to rise to that challenge. We are grateful to them for acknowledging the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study which we believe to be the largest prospective cohort of the practice, with 512 patients recruited. It provides baseline data to randomized controlled trial (RCT) standards (2). Nested within it is the only RCT that has ever addressed the question (3). While we appreciated PulMiCC being mentioned, we do not think it is adequately represented in their narrative. But we will return to that in due course. First we would like to parse their concluding sentence to tease out some points. They specify that a trial must be “large”. The size of the trial required to produce trustworthy evidence is inversely proportional to the effect size. The smaller the effect size the larger is the trial required to detect the difference. Conversely if there is a large effect relatively few patients are required to show it. For the question of lung metastasectomy the US Society of Thoracic Surgeons (STS)—which might be expected to be one of the betterinformed bodies of opinion on the matter—concluded that without operation, five-year survival can be assumed be zero among patients with lung metastases (4). An editorial in the European Journal of Cardio-Thoracic Surgery (EJCTS) claimed that survival with metastasectomy is as high as 60% (5). Neither statement was supported by a systematic review of numerical evidence. Both teams of authors knew that the question was being tested in the PulMiCC trial, and they mention the trial. But in their narratives, they chose to dismiss it before it had even been published. If both estimates had been correct, it would indicate a really large effect size of 60%. That means that for two groups of 10 patients expected survival might be, 6/10 versus 0/10 which by Fisher’s exact test would be highly significant (P=0.018). A difference of anywhere close to that magnitude would have signalled in the PulMiCC RCT of 93 patients but it was nowhere to be seen (lower panel of the figure). By specifying that the trial must be “large” Mak and Hsin inadvertently accept that the benefit attributable to localise treatment of lung metastases from colorectal cancer must be small, and much less than is widely claimed. Our re sea rch in p l ann ing the RCT inc luded mathematical modelling (6). We were convinced then by the data that if there was any benefit it would be much Editorial