Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed.

M Milosevic,B Davidson,V Farewell,T Treasure,A Marchbank,S Grumett,T Batchelor,J Hasan,A Coonar,N.R Williams,F Macbeth,M Shackcloth,D Tsang,J Edwards,J Dunning

doi:10.1111/codi.15113

Abstract

AimLung metastases from colorectal cancer are resected in selected patients in the belief that this confers a significant survival advantage. It is generally assumed that the 5‐year survival of these patients would be near zero without metastasectomy. We tested the clinical effectiveness of this practice in Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC), a randomized, controlled noninferiority trial.MethodMultidisciplinary teams in 14 hospitals recruited patients with resectable lung metastases into a two‐arm trial. Randomization was remote and stratified according to site, with minimization for age, sex, primary cancer stage, interval since primary resection, prior liver involvement, number of metastases and carcinoembryonic antigen level. The trial management group was blind to patient allocation until after intention‐to‐treat analysis.ResultsFrom 2010 to 2016, 93 participants were randomized. These patients were 35–86 years of age and had between one and six lung metastases at a median of 2.7 years after colorectal cancer resection; 29% had prior liver metastasectomy. The patient groups were well matched and the characteristics of these groups were similar to those of observational studies. The median survival after metastasectomy was 3.5 (95% CI: 3.1–6.6) years compared with 3.8 (95% CI: 3.1–4.6) years for controls. The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93 (95% CI: 0.56–1.56). Use of chemotherapy or local ablation was infrequent and similar in each group.ConclusionPatients in the control group (who did not undergo lung metastasectomy) have better survival than is assumed. Survival in the metastasectomy group is comparable with the many single‐arm follow‐up studies. The groups were well matched with features similar to those reported in case series.

Highlights

The lung is a common site of metastases and, since the earliest days of chest radiography, has been the site where metastases are most detected
The median survival after metastasectomy was 3.5 years compared with 3.8 years for controls
The estimated unadjusted hazard ratio for death within 5 years, comparing the metastasectomy group with the control group, was 0.93

Summary

Results

The first randomization was 2 December 2010 and the last was 24 November 2016. The randomized trial closed in December 2016 because of poor recruitment. Of the 93 patients randomized, 47 were assigned to the control group and 46 to metastasectomy. The clinical teams were subsequently allowed to treat as they judged clinically appropriate, and three patients in the control group had metastasectomy at 13, 19 and 27 months after randomization. Comparison of survival rates in the metastasectomy arm with those in the control arm, adjusting for and comparing patients with comparable minimization variables, gave an estimated hazard ratio of 0.87 with a 95% CI of 0.51–1.48. There is a numerical difference in estimated 5-year rates because there were seven (of 20) deaths in the control arm in year 5 and three (of 17) in the metastasectomy arm. Updated primary trial outcome analyses Restricting attention to 5 years of follow-up, as specified for the primary analysis of the trial, 58 deaths

Conclusion

Background

Study design

Ethical approval and consent to participate

Discussion