Baum, M

Fallowfield, L

Farewell, V

Macbeth, F

Treasure, T

English

UCL Discovery

Michael Baum, Lesley Fallowfield, Vern Farewell, Fergus Macbeth and Tom Treasure  The NICE recommendations to ‘consider’ surgical resection for colorectal cancer (CRC) metastases should worry those who value evidence informing surgical practice.(1) There are no randomised controlled trials (RCT) of liver metastasectomy primarily due to liver surgeons’ opposition.(2) The effectiveness of peritoneal cytoreductive surgery (CRS) could not be deduced from the RCTs cited, because it was in both arms.(1)  The evidence given supporting lung metastasectomy is poor: one retrospective observational study(3) judged by NICE reviewers to have ‘high risk of selection bias’ and ‘very low quality’. Patients selected not to have metastasectomy (N=57) had high rates of known adverse features: >3 metastases (67%), bilateral (65%), multi-lobe (77%), multi-organ (37%) and <12 months since primary resection (49%),  far higher than in the 48 selected for metastasectomy: 4%, 19%, 10%, 12.5% and 33% respectively. The full results of the PulMiCC RCT (N=93) addressing this question have now been published and show no significant difference between lung metastasectomy and controls.(4)  NICE recommended lung metastasectomy on the basis of the Committee’s ‘clinical experience’. Patients are offered metastasectomy in the widely held belief that without operation their 5-year survival would be <5%.(5) RCTs of local treatment of metastases (CLOCC(6), SABR-COMET(7) and PulMiCC(4)) show this to be mistaken. For example, survival without metastasectomy, in CLOCC and PulMiCC taken together, had a weighted combined estimate of 30% (95% confidence interval (21%,40%)) derived using a complementary log-log scale.  Any putative survival benefit attributable to metastasectomy is probably much smaller than believed. CRC lung metastases are rarely symptomatic, or the cause of death; generally, patients who have metastasectomy still die from progressive CRC. The research recommendation to compare two unproven treatments, surgery and SABR, would not test the effectiveness of either.  The ‘experts’ appear to have steered NICE guidance, without evidence, towards their own practice and convictions.  1. Mohamed F, Kallioinen M, Braun M, Fenwick S, Shackcloth M, Davies J. Management of colorectal cancer metastases to the liver, lung or peritoneum suitable for curative intent: summary of NICE guidance. Br J Surg. 2020. 2. Fenwick SW, Poston GJ, Cameron IC, Huguet E, Welsh FK. Re: E Morris, T Treasure, Cancer Epidemiology, 49 (2017) 152-155. Cancer Epidemiol. 2018;52:158-9. 3. Kim CH, Huh JW, Kim HJ, Lim SW, Song SY, Kim HR, et al. Factors influencing oncological outcomes in patients who develop pulmonary metastases after curative resection of colorectal cancer. Dis Colon Rectum. 2012;55(4):459-64. 4. Milosevic M, Edwards J, Tsang D, Dunning J, Shackcloth M, Batchelor T, et al. Pulmonary Metastasectomy in Colorectal Cancer (PulMiCC): Updated analysis of 93 randomised patients - control survival is much better than previously assumed. Colorectal Disease. 2020;IN PRESS. 5. Beavis J, Buchan K. Re: Colorectal Cancer:summary of NICE guidance. BMJ [Internet]. 2020. Available from: https://www.bmj.com/content/368/bmj.m461/rapid-responses. 6. Ruers T, van Coevorden F, Punt CJ, Pierie JE, Borel-Rinkes I, Ledermann JA, et al. Local Treatment of Unresectable Colorectal Liver Metastases: Results of a Randomized Phase II Trial. J Natl Cancer Inst. 2017;109(9). 7. Palma DA, Olson R, Harrow S, Gaede S, Louie AV, Haasbeek C, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051-8. 

NICEGuidelines: management of colorectal cancer metastases

https://discovery.ucl.ac.uk/id/eprint/10127394/1/Baum%20et%20al%20BJS%20re%20NICE%20Draft%20May%202020.pdf

NICEGuidelines: management of colorectal cancer metastases

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