What have we learned in the process of setting up and running the PulMiCC (Pulmonary Metastasectomy in Colorectal Cancer) randomised controlled trial?

Abstract

: The majority of lung metastasectomy operations are for colorectal cancer (CRC). The practice is highly selective. Of patients who have had a potentially curative resection, about 2–3% subsequently have a lung metastasectomy. The motive for operation is to cure the patient by removing the only evident remaining cancer. We review the methods used to investigate the evidence on which this practice is based, going from review of published observational cohort studies, through a citation network to a randomised controlled trial (RCT). The non-inferiority RCT Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) compared survival, quality of life, and health utility in 46 patients randomised to metastasectomy and 47 control patients. The two arms were well balanced for the known prognostic characteristics: the number of metastases, carcinoembryonic antigen levels, previous liver metastasectomy, cancer stage, and the interval since primary resection. Median survival was similar in the two arms: 3.5 years after metastasectomy and 3.8 years among controls and hazard ratio for death within five years of 0.93 (95% CI: 0.56–1.56). There were 12 five-year survivors after metastasectomy and 11 among controls. The size of the trial does not exclude the possibility of occasional long-term survivors in whom metastasectomy appears to have removed the only residue of cancer, as has been observed anecdotally. As might be expected, after metastasectomy there was a decline in lung function as measured by % predicted FEV1. There were also more lung symptoms among the patient reported outcomes. The decline in self-reported health state was similar in the two arms. The generally assumed near zero five-year survival without metastasectomy was not found in PulMiCC or in the control groups of two other randomised studies, CLOCC and SABRE-COMET. Patients, and those treating for them, should be aware of this new information in reaching a decision about lung metastasectomy.