Pulmonary metastasectomy in colorectal cancer: PulMiCC and future trials.

Quant Imaging Med Surg 2020;10(11):2215-2217 | http://dx.doi.org/10.21037/qims-20-774 Marcus Taylor and colleagues provide an excellent summary of the present situation with respect to the treatment of lung metastases from colorectal cancer (CRC), but we don’t agree with the specific research question they propose to test in a randomized trial. They write: ‘In conclusion, there remains very little high-quality evidence demonstrating the benefit of any form of intervention in this patient group and hence a controlled trial comparing overall survival between patients undergoing surgical metastasectomy, SABR or RFA for biopsy-proven metastatic colorectal cancer is required to address the question of which modality provides superior outcomes in this cohort of patients.’ (1). In their review they found no good evidence for benefit of any of these local treatments of metastases and so, we contend, it would be irrational to do a randomized controlled trial (RCT) making a comparison between any of them. Unless you know there is benefit, which requires a non-interventional arm, all you might show is which does less harm. Otherwise you would, unknowingly, interpret the difference as a greater benefit. The paper by Hasegawa on which Taylor et al. comment includes 70 patients with a predominance of favorable features for longer than average survival. Ten departments took more than 6 years to select and accrue these patients and so it is likely that they were highly selected. But we are provided with no denominator. In 79% of them the prognostic indicators were good: metastases were solitary, the mean size was 1 cm, 66% of had no CEA elevation, and there was a mean interval since primary CRC resection of more than 3 years (2). As Taylor et al. observe there were also very few histological confirmations. The 3-year survival was 84%. At the same time point, survival in the non-metastasectomy arm of the RCT Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) was 70% (3). These were patients eligible for metastasectomy but not as highly selected as in Hasegawa’s RFA report. The difference in survival may simply be due to higher selection and a better prognosis. The belief in the clinical benefit of surgical lung metastasectomy has been entirely based on an assumption that 5-year survival would be zero, or close to it, if the lung metastases had not been removed (4). This assumption has been robustly challenged by the STS working group on lung metastasectomy. They could find no evidence to support this belief among over 1,000 papers. They state emphatically that the assumption of zero mortality is not supported by the literature (5). The zero belief was somewhat modified in the systematic review by Gonzalez et al. who wrote that survival is ‘worse than 5%’ (6). In support they cited a paper, from more than Letter to the Editor