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

Abstract

Aim Lung 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. Method Multidisciplinary 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. Results From 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. Conclusion Patients 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.

Pulmonary metastasectomy in colorectal cancer: health utility scores by EQ‐5D‐3L in a randomized controlled trial show no benefit from lung metastasectomy

“…It is most often used in health economics studies to generate quality adjusted life years. The PulMiCC EQ‐5D‐3L results reported here complement the trial survival data [1] (Figure 1) and will contribute to a future health economics evaluation.…”

Cytoreductive surgery and HIPEC in colorectal cancer—did we get hold of the wrong end of the stick?

“…In summary CRC, even in the metastatic setting has become a disease amenable to surgical treatments and the prognosis of patients with PM has considerably improved. In different indications there are multimodal approaches, combining metastasectomy (liver/lung) with systemic chemotherapy that lead to unexpected long-term survival [28,29]. Against this background it is noteworthy that the PRODIGE 7 trial has also established an impressive median OS of >41 months with CRS alone [19].…”

Sample size calculations for randomized controlled trials and for prediction models

“…As we said, the actual sample size calculation may be much more complicated. In fact, the PulMiCC trial was powered for non-inferiority of leaving the metastases unresected using time to event analysis [10]. With this smaller difference (40% and 30%) the numbers needed to power the study were commensurately higher, and in the event not achievable due to the tenacity with which cancer teams held on to the near zero assumption and its implications [11,12].…”

“…The outcome of importance is survival. For lung metastasectomy, results are usually given as survival rate, usually at an interval of 5 years, but there are too many factors and uncertainties to conclude that metastasectomy has a survival benefit by observation alone [3].…”