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Lung cancer screening with low dose computed tomography

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1970 (Published 07 March 2014) Cite this as: BMJ 2014;348:g1970

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Re: Lung cancer screening with low dose computed tomography

I am surprised that Baldwin et al are so confident of the benefits of lung cancer screening with low-dose CT (LDCT). The NLST, in finding a 20% reduction in mortality from screening with LDCT, in comparison to plain X-ray screening, which itself is ineffective, suggests that screening may be one strategy for improving lung cancer outcomes in a well-motivated American population. However, the absolute reduction in mortality achieved is small: 87 avoided deaths in 26,722 screened participants, representing a 0.33% lower risk of dying from lung cancer for each individual participant. A massive 24% of participants were found to have a nodule over 3 rounds, leading to further diagnostic work up. Even in these large academic institutions, a major complication occurred in 5 of every 10,000 cases with a benign nodule.

Overall, for every cancer death avoided, 1.38 cases may have been overdiagnosed [1]. Furthermore, the figures for overdiagnosis may have been worse if the control arm had received no chest radiographs. The risk of overdiagnosis, as might be expected, depends on histological sub-type and is most striking in patients with a diagnosis of broncho-alveolar cell carcinoma, now more correctly termed minimally invasive adenocarcinoma, in whom the risk of overdiagnosis was estimated to be 85% after 7 years of follow-up or 49% with lifetime follow-up [1]. These data raise the question as to the necessity and type of therapy required if a diagnosis of minimally invasive adenocarcinoma is established.

Because the major risk factor for lung cancer is the smoking of tobacco, in order to qualify for entrance into a screening program, individuals need to have consumed substantial amounts of tobacco and many will be current cigarette smokers. Consequently, the target population of a lung cancer screening programme may be expected to have a relative disregard for its own health and a tendency to accept of risk, potentially predisposing to poor acceptability of and adherence to screening. Indeed, it has been shown that smokers in the USA are significantly more likely than never smokers to be male, non-white, less educated, to report poor health status and to be less likely to be able to identify a usual source of healthcare [2]. This study also indicated that current smokers were less likely than never smokers to believe that early detection would result in a good chance of survival and expressed relative reluctance to consider computed tomography screening for lung cancer. Interestingly only half of these smokers stated that they would opt for surgery for a screen-diagnosed cancer, further calling into question the value of early diagnosis in this group.

Of greatest concern in extrapolating the positive results of the NLST, none of the European studies have found evidence of any significant, or indeed even a trend towards, reduction in mortality. The epidemiology of cancer subtypes and benign nodule prevalence is very different in the different populations. In the UK, squamous cancers represent about 40% of cancers and adenocarcinomas 18%, whilst in the USA squamous cancers only represent 27% with adenocarcinoma being the most prevalent type at 31% [3]. As squamous cancers tend to arise in more often in proximal airways they are less amenable to identification as a lung nodule on CT, unlike adenocarcinomas, which more often present as intrapulmonary nodules. A longer screening interval and the use of volumetric techniques employed in the NELSON study seems attractive, but they remain completely unproven. The DANTE and DLCST have employed similar protocols to the NLST but have not so far found any reduced mortality.

Concentration on harm reduction through screening potentially deflects attention from other approaches. In particular it is known that patients often tolerate lung cancer symptoms for long periods before presenting with them [4]. Furthermore, general practitioners find identifying lung cancer cases challenging and patients will often attend several times before the diagnosis is considered and a chest radiograph performed [5]. An early study revealed that educating the public and primary health care teams on the importance of cough as a lung cancer symptom resulted in a large increase in chest radiographs being performed and suggested earlier diagnosis [6]. This has led on to the national “Be Clear on Cancer” campaign in the UK. It is believed that the results of the first campaign have been positive, leading to state funding of a repeat programme in 2013. Facilitating earlier diagnosis of symptomatic disease should reduce the risk of overdiagnosis. Further work is taking place to look at the effects of lowering thresholds for the obtaining of chest radiographs for chest symptoms in primary care [7].

I believe that screening in lung cancer is potentially able to improve mortality in a highly motivated US population, but our understanding of how to apply this in real populations, including those outside the USA, is in its infancy. Interestingly, costs are much reduced when combined with smoking cessation, and given that participating in a screening programme does not appear to promote quitting, it may be that much of the benefit arises purely from the smoking cessation element.

Furthermore, the considerable costs of screening need to be balanced against the small but definite harms resulting from radiation exposure, investigations of benign lesions and the more significant difficulty of finding of inconsequential disease (overdiagnosis). Until we have better understanding of these issues, I believe we should be concentrating on the earlier diagnosis of symptomatic disease, at least in the UK.

References

1. Patz, E.F., et al., Overdiagnosis in Low-Dose Computed Tomography Screening for Lung Cancer. JAMA internal medicine, 2013: p. ---.
2. Silvestri, G.A., et al., Attitudes towards screening for lung cancer among smokers and their non-smoking counterparts. Thorax, 2007. 62(2): p. 126-130.
3. Youlden, D.R., S.M. Cramb, and P.D. Baade, The International Epidemiology of Lung Cancer: Geographical Distribution and Secular Trends. Journal of Thoracic Oncology, 2008. 3(8): p. 819-831 10.1097/JTO.0b013e31818020eb.
4. Corner, J., et al., Is late diagnosis of lung cancer inevitable? Interview study of patients' recollections of symptoms before diagnosis. Thorax, 2005. 60(4): p. 314-319.
5. Bowen, E.F. and C.F. Rayner, Patient and GP led delays in the recognition of symptoms suggestive of lung cancer. Lung Cancer, 2002. 37(2): p. 227-228.
6. Athey, V.L., et al., Early diagnosis of lung cancer: evaluation of a community-based social marketing intervention. Thorax, 2012. 67(5): p. 412-7.
7. Hurt, C.N., et al., A feasibility study examining the effect on lung cancer diagnosis of offering a chest X-ray to higher-risk patients with chest symptoms: protocol for a randomized controlled trial. Trials, 2013. 14: p. 405.

Competing interests: No competing interests

29 March 2014
Trevor K Rogers
Chest Physician
Doncaster Royal Infirmary
Armthorpe Road, Doncaster, DN2 5LT