Controlled Trial Data Casts Doubt on the Supposed Benefit of Lung Metastasectomy. Comment on Chandra et al. The Colorectal Cancer Tumor Microenvironment and Its Impact on Liver and Lung Metastasis. Cancers 2021, 13, 6206.

We read with interest the comprehensive review by Chandra et al. [...].

Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial: a systematic review of published responses.

OBJECTIVES: The objective of this review was to assess the nature and tone of the published responses to the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) randomized controlled trial. METHODS: Published articles that cited the PulMiCC trial were identified from Clarivate Web of Science (©. Duplicates and self-citations were excluded and relevant text was extracted. Four independent researchers rated the extracts independently using agreed scales for the representativeness of trial data and the textual tone. The ratings were aggregated and summarized. Two PulMiCC authors carried out a thematic analysis of the extracts. RESULTS: Sixty-four citations were identified and relevant text was extracted and examined. The consensus rating for data inclusion was a median of 0.25 out of 6 (range 0-5.25, interquartile range 0-1.5) and, for textual tone, the median rating was 1.87 out of 6 (range 0-5.75, interquartile range 1-3.5). The majority of citations did not provide adequate representation of the PulMiCC data and the overall textual tone was dismissive. Although some were supportive, many discounted the findings because the trial closed early and was underpowered to show non-inferiority. Two misinterpreted the authors' conclusions but there was an acceptance that 5-year survival was much higher than widely assumed. CONCLUSIONS: Published comments reveal a widespread reluctance to consider seriously the results of a carefully conducted randomized trial. This may be because the results challenge accepted practice because of 'motivated reasoning', but there is a widespread misunderstanding of the fact that though PulMiCC with 93 patients was underpowered to test non-inferiority, it still provides reliable evidence to undermine the widespread belief in a major survival benefit from metastasectomy.

The full cohort of 512 patients and the nested controlled trial in 93 patients in the Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) study raise doubts about the effective size at present claimed.

A comparison of the relative merits of video-assisted pulmonary metastasectomy versus thoracotomy is predicated on the assumption that removal of asymptomatic lung metastases favourably influences survival and that it does so by a large degree. Recently published but long-awaited evidence from a prospective cohort study and a randomised trial of Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) challenges that assumption.