BMJ 2014;348:g1970 doi: 10.1136/bmj.g1970 (Published 7 March 2014)
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Editorials
EDITORIALS Lung cancer screening with low dose computed tomography Now recommended in the US, but what about the UK? 1
2
David R Baldwin consultant respiratory physician , David M Hansell professor of thoracic imaging , 3 Stephen W Duffy professor of cancer screening , John K Field director of research, Roy Castle 4 Research Programme Respiratory Medicine Unit, David Evans Research Centre, Nottingham University Hospitals, Nottingham NG5 1PB, UK; 2Department of Radiology, Royal Brompton and Harefield NHS Foundation Trust, London, UK; 3Wolfson Institute of Preventive Medicine, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 4Roy Castle Lung Cancer Research Programme, University of Liverpool Cancer Research Centre, Liverpool, UK 1
Lung cancer is a health problem that clearly merits a screening programme. Each year about 35 000 people in the United Kingdom die from lung cancer—more than the number for colorectal and breast cancer combined. In addition, about three quarters of people present with incurable disease, at a stage when treatment has little effect on overall survival; early stage disease is curable; risk factors for lung cancer are well understood; and a highly sensitive screening test is available.
criteria, level of harm, optimal clinical pathways, and cost effectiveness.3 Better selection for screening using a risk prediction model has been shown to prevent more deaths per person screened, with a reduction in the number needed to screen to prevent one death in NLST from 320 to 270.4 If screening is restricted to those with a greater than 1.25% risk of death from lung cancer over five years, this number falls to 166.5
The National Lung Screening Trial (NLST) randomised more than 53 400 people in the United States aged 55-74 years who had smoked in the past 15 years and had accumulated a minimum of 30 pack years to three annual screens with low dose computed tomography or chest radiography.1 The trial recruited between 2002 and 2004, and in October 2010 it was stopped one year earlier than planned because the prespecified lung cancer mortality reduction of 20% had been reached in the low dose computed tomography arm. The trial also showed a reduction in all cause mortality of 6.7%.
Computed tomography detects about 25 benign lesions for every cancer detected. In NLST, 0.2% (59/26 722) of participants underwent a computed tomography guided lung biopsy for a non-cancerous lesion, and seven (0.03%) had a major complication.1 Overdiagnosis occurs when indolent cancers are detected in people who would not die from the cancer. These people do not benefit from early diagnosis but are subject to the same harms as others from investigations, treatment, and the psychological impact of being told they have cancer. Estimates based on the excess seen in NLST and in lead time estimation from various sources suggest that 10-20% of screen detected cancers are overdiagnosed (18.5% in NLST).7 8 Although, arguably, the benefits outweigh the harms, harms can be reduced further. The Dutch-Belgian NELSON trial and the UK Lung Screen pilot trial both use volumetric measurements to detect growth, with management of abnormal findings governed by protocol.9 10 This reduces the number of false positive screens, defines more accurately the need for invasive procedures, and may reduce overdiagnosis.
Many of the early trials of screening with chest radiography and the non-randomised computed tomography studies were not designed to minimise the biases operating in screening trials that result in apparently longer survival but no reduction in mortality. The answer to this problem was to design randomised controlled trials with disease specific mortality as the endpoint.
Several US professional organisations have since recommended that screening be introduced for people of the same age and smoking habit as those in NLST. After a commissioned independent analysis of the evidence, the US Preventive Services Taskforce recommended that lung cancer screening should be offered to people with comparable risk to those in NLST, but with the upper the age limit extended to 80 years.2 A decision about the introduction of such screening in the UK awaits assimilation of the available evidence about selection
Physical harms may result from radiation, further investigation of abnormal findings, and treatment. The radiation dose used in low dose computed tomography is about a fifth of that typically used in thoracic computed tomography, less than half a person’s annual background radiation dose. Annual screening with this technique is estimated to cause one radiation induced lung cancer death for every 22 deaths prevented.6
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BMJ 2014;348:g1970 doi: 10.1136/bmj.g1970 (Published 7 March 2014)
Page 2 of 2
EDITORIALS
Psychological harm has been shown to be minimal in screening trials. Anxiety and distress increase transiently in people with positive or indeterminate findings but return to baseline after the second screen.11 Distress and fear of cancer decreased in subjects with negative results compared with baseline. Whether people may be falsely reassured and continue, or even start, smoking is not known: smoking cessation rates in NELSON were 14.5% in the low dose computed tomography arm compared with 19.1% in the control arm; both of these were higher than the 6-7% background rate.12 Evidence for cost effectiveness is based on modelling, largely using findings from NLST. Although some models yield higher costs, these reduce when the benefit of smoking cessation is included. The most detailed model gave an incremental cost effectiveness ratio of $23 000 (£13 786; €16 746) when it included a basic smoking cessation intervention, and this improved to $17 000 with a more intensive regimen (varenicline plus behavioural techniques). This study also showed that efficient clinical and radiological follow-up protocols will be crucial to the design of the most cost effective programmes.13 Healthcare professionals who care for patients with lung cancer recognise that screening can prevent suffering and save lives but they also understand that harms must be minimised and screening has to be cost effective. Biennial or annual screening between ages 60 and 75 years in those with a risk of lung cancer in excess of 1% per annum, with clear protocols for the management of abnormal findings, would probably achieve this while we await research evidence that will help refine programme design.14 In February this year, the UK screening committee received a detailed new policy proposal from members of the UK Lung Screen study setting out the evidence and key problems so that recommendations can be made about implementation. In addition, the Department of Health’s science and technology committee has called for submissions regarding evidence for screening, including for lung cancer; we hope for a favourable outcome.
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Competing interests: “We have read and understood the BMJ Group policy on declaration of interests and declare the following interests: All authors are members of the UKLS study group. Provenance and peer review: Commissioned; not externally peer reviewed. 1 2 3 4 5 6 7 8 9 10 11 12 13 14
National Lung Screening Trial Research Team; Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, et al. Reduced lung-cancer mortality with low-dose computed tomographic screening. N Engl J Med 2011;365:395-409. Humphrey LL, Deffebach M, Pappas M, Baumann C, Artis K, Mitchell JP, et al. Screening for lung cancer with low-dose computed tomography: a systematic review to update the US Preventive services task force recommendation. Ann Intern Med 2013;159:411-20. Field JK, Aberle DR, Altorki N, Baldwin DR, Dresler C, Duffy SW, et al. The International Association Study Lung Cancer (IASLC) strategic screening advisory committee (SSAC) response to the USPSTF recommendations. J Thorac Oncol 2014;9:141-3. Tammemagi MC, Katki HA, Hocking WG, Church TR, Caporaso N, Kvale PA, et al. Selection criteria for lung-cancer screening. N Engl J Med 2013;368:728-36. Kovalchik SA, Tammemagi M, Berg CD, Caporaso NE, Riley TL, Korch M, et al. Targeting of low-dose CT screening according to the risk of lung-cancer death. N Engl J Med 2013;369:245-54. De Koning HJ, Meza R, Plevritis SK, Ten Haaf K, Munshi VN, Jeon J, et al. Benefits and harms of computed tomography lung cancer screening strategies: a comparative modeling study for the US Preventive Services Task Force. Ann Intern Med 2014;160:311-20. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. Lancet 2012:380:1778-86. Duffy SW, Field JK, Allgood PC, Seigneurin A. Translation of research results to simple estimates of the likely effect of a lung cancer screening programme in the United Kingdom. Br J Cancer 2014; published online 13 Feb. Van Klaveren RJ, Oudkerk M, Prokop M, Scholten ET, Nackaerts K, Vernhout R, et al: Management of lung nodules detected by volume CT scanning. N Engl J Med 2009;361:2221-9. Baldwin DR, Duffy SW, Wald NJ, Page R, Hansell DM, Field JK. UK Lung screen (UKLS) nodule management protocol: modelling of a single screen randomised controlled trial of low-dose CT screening for lung cancer. Thorax 2011;66:308-13. Van den Bergh KA, Essink-Bot ML, Borsboom GJ, Scholten ET, van Klaveren RJ, de Koning HJ. Long-term effects of lung cancer computed tomography screening on health-related quality of life: the NELSON trial. Eur Respir J 2011;38:154-61. Van der Aalst CM, van den Bergh KA, Willemsen MC, de Koning HJ, van Klaveren RJ. Lung cancer screening and smoking abstinence: 2 year follow-up data from the Dutch-Belgian randomised controlled lung cancer screening trial. Thorax 2010;65:600-5. Villanti AC, Jiang Y, Abrams DB, Pyenson BS. A cost-utility analysis of lung cancer screening and the additional benefits of incorporating smoking cessation interventions. PLoS One 2013;8:e71379. Field JK, Hansell DM, Duffy SW, Baldwin DR. CT screening for lung cancer: countdown to implementation. Lancet Oncol 2013;14:e591-600.
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