Abstract
BackgroundLung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. We aimed to test its effectiveness in a randomised controlled trial (RCT).MethodsMultidisciplinary teams in 13 hospitals recruited participants with potentially resectable lung metastases to a multicentre, two-arm RCT comparing active monitoring with or without metastasectomy. Other local or systemic treatments were decided by the local team. Randomisation was remote and stratified by site with minimisation for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, the number of metastases, and carcinoembryonic antigen level. The central Trial Management Group were blind to patient allocation until completion of the analysis. Analysis was on intention to treat with a margin for non-inferiority of 10%.ResultsBetween December 2010 and December 2016, 65 participants were randomised. Characteristics were well-matched in the two arms and similar to those in reported studies: age 35 to 86 years (interquartile range (IQR) 60 to 74); primary resection IQR 16 to 35 months previously; stage at resection T1, 2 or 3 in 3, 8 and 46; N1 or N2 in 31 and 26; unknown in 8. Lung metastases 1 to 5 (median 2); 16/65 had previous liver metastases; carcinoembryonic antigen normal in 55/65. There were no other interventions in the first 6 months, no crossovers from control to treatment, and no treatment-related deaths or major adverse events. The Hazard ratio for death within 5 years, comparing metastasectomy with control, was 0.82 (95%CI 0.43, 1.56).ConclusionsBecause of poor and worsening recruitment, the study was stopped. The small number of participants in the trial (N = 65) precludes a conclusive answer to the research question given the large overlap in the confidence intervals in the proportions still alive at all time points. A widely held belief is that the 5-year absolute survival benefit with metastasectomy is about 35%: 40% after metastasectomy compared to < 5% in controls. The estimated survival in this study was 38% (23–62%) for metastasectomy patients and 29% (16–52%) in the well-matched controls. That is the new and important finding of this RCT.Trial registrationClinicalTrials.gov, ID: NCT01106261. Registered on 19 April 2010
Highlights
Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit
The report contains data on patients who had had a lung metastasectomy performed by the contributing surgeons but, as is typical in procedure-based clinical reporting, there were no comparable data on those who did not have metastases removed
One small comparative study was published in 1980 [4]. It reported that the survival of 12 patients who were potential candidates for metastasectomy but did not have it was not dissimilar to 70 comparable patients who had had lung metastasectomy
Summary
Lung metastasectomy in the treatment of advanced colorectal cancer has been widely adopted without good evidence of survival or palliative benefit. Standard care of colorectal cancer patients includes detection by active surveillance of asymptomatic metastases followed by surgical resection in selected patients. Lung metastasectomy is regarded as ‘a pillar of modern thoracic surgery’ [1] and is a substantial component of the work of thoracic surgical units internationally. This activity has been reported increasingly in clinical case series from the 1960s [2]. In 2013 a meta-analysis of the 25 largest single-arm follow-up studies from 2000 to 2011, reported an overall 5-year survival rate of 41% for patients having lung metastasectomy for colorectal cancer, at an average interval of about 2 years after primary resection. No controlled studies were found and the authors concluded that ‘the benefit attributable to surgery is neither immediate nor irrefutable’ [8]
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