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We congratulate Sponholz and colleagues on their study showing the favourable impact of a left colon primary site on survival following lung metastasectomy for colorectal cancer (CRC). The survival rate for these patients is truly impressive. The difference attributable to primary site of CRC confirms the recently published study from the MD Anderson Cancer Centre and emphasises the influence of inherent biological factors on survival [1].
The authors kindly mentioned the randomised controlled trial (RCT) Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC) citing a preliminary analysis [2]. There was no difference in quality of life or health utility [3]. The full randomised trial (N=93) has since been published [4]. It is not a fair representation of events to say PulMiCC “was stopped because of poor recruitment”. The study recruited well, reaching a cohort of 512 patients. The difficulty was confined to randomisation due to the widespread assumption that survival without operation would be 0 and its corollary, that all 5-year survival is attributable to metastasectomy [5]. PulMiCC was closed in an orderly fashion so that it could be analysed to inform practice.
The intervention and control arms in the PulMiCC RCT were well matched for age, sex, carcinoembryonic antigen, prior liver metastases, primary cancer stage, interval since primary resection and the number of metastases. There was no demonstrable difference in survival at any time point up to 5 years. The revelation from PulMiCC was the magnitude of control survival which was 47.1% (95% CI: 31.9–62.6%) at 4 years. The median survival was in fact longer in the control arm (46 versus 42 months).[4] We cannot exclude an eventual survival benefit from metastasectomy but it must be much smaller than the widely believed ~40%. The findings of the cohort study, soon to be published, provide further insights into the effects of biological factors on survival.
References
Corsini EM, Mitchell KG, Correa A, Morris VK, Antonoff MB, MD Anderson Pulmonary Metastasectomy Working Group (2020) Effect of primary colorectal cancer tumor location on survival after pulmonary metastasectomy. J Thorac Cardiovasc Surg. https://doi.org/10.1016/j.jtcvs.2020.03.181
Treasure T, Farewell V, Macbeth F, Monson K, Williams NR, Brew-Graves C et al (2019) Pulmonary Metastasectomy versus Continued Active Monitoring in Colorectal Cancer (PulMiCC): a multicentre randomised clinical trial. Trials. 20(1):718
Brew-Graves C, Farewell V, Monson K, Milosevic M, Williams N, Morris E et al (2021) Pulmonary Metastasectomy in Colorectal Cancer: Health Utility scores by EQ-5D-3L in a randomised controlled trial show no benefit from lung metastasectomy. Color Dis 23(1):200–205
Milosevic M, Edwards J, Tsang D, Dunning J, Shackcloth M, Batchelor T, Coonar A, Hasan J, Davidson B, Marchbank A, Grumett S, Williams NR, Macbeth F, Farewell V, Treasure T (2020) Pulmonary Metastasectomy in Colorectal Cancer: updated analysis of 93 randomized patients - control survival is much better than previously assumed. Color Dis 22(10):1314–1324
Handy JR, Bremner RM, Crocenzi TS, Detterbeck FC, Fernando HC, Fidias PM, Firestone S, Johnstone CA, Lanuti M, Litle VR, Kesler KA, Mitchell JD, Pass HI, Ross HJ, Varghese TK (2019) Expert consensus document on pulmonary metastasectomy. Ann Thorac Surg 107(2):631–649
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Tom Treasure Chief Investigator of the PulMiCC Trial
Misel Milosevic Lead Principal Investigator of the PulMiCC Trial
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Treasure, T., Milosevic, M. Surgery, selection or biology in lung metastasectomy for colorectal lung metastasectomy? PulMiCC may not provide all the answers but it does narrow down the question. Int J Colorectal Dis 36, 2281 (2021). https://doi.org/10.1007/s00384-021-03916-8
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DOI: https://doi.org/10.1007/s00384-021-03916-8