Respiratory Oncology Unit (Department of Pulmonology) and Leuven Lung Cancer Group, University Hospital Gasthuisberg, Leuven, Belgium.
The authors declare no conflict of interest.
Address for correspondence: Johan Vansteenkiste, MD, PhD, Respiratory Oncology Unit (Pulmonology), University Hospital Gasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. E-mail: email@example.com
After the disappointing experience with lung cancer screening studies based on chest x-ray and/or sputum cytology several decades ago, great expectations are now in place on screening with modern low-dose spiral computed tomography (LDSCT) scan. The prevalence data of one of these randomized studies is reported in this issue of our journal.1
The definition of screening—adapted from Stedman’s Concise dictionary—consists of an examination of a group of usually asymptomatic individuals to detect those with a high probability of having a given disease, typically by means of an inexpensive, safe, and well-performing diagnostic test.2 To reach the real goal—reduction of lung cancer related mortality—four conditions need to be in place: a sensitive test for detection of small lesions; small lesions need to be associated with truly early stage disease; an effective treatment is available for these lesions; and acceptable morbidity and cost of the screening tool.
Screening for lung cancer by LDSCT has been studied extensively in the past decade, and it looks like this might become the long awaited tool. Looks like, because until today, all the available data have been gathered from many—some even very large—cohort studies, but not yet from large randomized controlled trials. These nonrandomized studies show promising results. In the I-ELCAP trial in asymptomatic smokers or past smokers, for instance, 85% of lung cancers were detected in stage I, and the estimated 10-year survival rate of patients whose stage I lung cancer was removed by surgery was 92%.3 This suggests that LDSCT is a sensitive tool that is able to detect small lesions associated with truly early stage, for which an effective therapy is available. This does not prove, however, that the strategy results in a reduction of lung cancer related mortality. This evidence can only come from the eagerly awaited results from two large randomized controlled trials that are currently running, the American National Lung Screening Trial, started in 2002, and the Dutch-Belgian Nederlands-Leuvens Longkanker Screening Onderzoek (NELSON) trial, started in 2003.4,5 The long-term postscreening follow-up on the primary end point of reduction of lung cancer mortality in participants in the National Lung Screening Trial and the NELSON trial is planned to end in 2009 and 2014, respectively. Until then, the “pro and con debate” on CT screening for lung cancer will probably remain a “battle over lung scans.”6,7
Some other, smaller RCTs have been setup in Italy, France, and in Denmark, the Danish randomized lung cancer CT screening trial (DLCST), whose first round or prevalence CT results are reported now.1 This DLCST has been designed in accordance with the NELSON trial to allow pooling of both study data together once both screening trials will have been finished. The combined data on lung cancer-specific mortality of around 20,000 included individuals will then give these two CT lung cancer screening trials an 80% power to show a lung cancer mortality reduction of at least 25%.5
Although waiting for the final results of these trials’ follow-up period by the year 2014, it is interesting to compare the first round CT screening results of the DLCST to the previously reported results from other series. The lung cancer detection rate of 0.83% (17 cases of lung cancer in 2052 participants) is lower than previously reported in nonrandomized CT screening trials. As pointed out by the authors, this result is not easily explainable at this time, and results of the lung cancer prevalence in their control group also need to be awaited. What is probably more important is the stage distribution of lung cancers that were detected in the randomized Danish trial: only 53% of screen detected lung cancers were stage I, definitely lower than in the International Early Lung Cancer Action Program trial. Around 65% of all screen-detected lung cancers in the DLCST could be surgically resected. How this all will translate into better prognosis, improved lung cancer survival and, most importantly, lower lung cancer mortality figures for the screening participants is very difficult to predict at present.
Even if lung cancer screening with LDSCT would become a validated screening method, its applicability in large parts of the world will be debated, for its safety and cost-effectiveness. One issue will be the most appropriate algorithm to be used for further diagnosis of noncalcified nodules that will often be detected on LDSCT, to reduce the number of invasive tests for benign nodules, and whether this algorithm can be improved by, e.g., use of more precise estimations of growth by computer-aided volumetric measurements, or by selective use of 18Fluorodeoxyglucose-positron emission tomography scan.8 Another question will be the exact definition of a high-risk population to target for lung cancer screening. Lung cancer risk models (such as the Liverpool Lung Project model) combining different epidemiological risk factors besides smoking history have been developed and will also need to be further validated.9
Until that time, we strongly endorse different international medical society guidelines that screening for lung cancer in asymptomatic individuals with LDSCT is not ready for widespread clinical practice in 2009.10,11 Recently reported efforts of total body screening of healthy individuals with CT scan, magnetic resonance imaging, or even FDG-positron emission tomography scan12 similarly belong in clinical trial settings at present. It would be an error to promote LDSCT screening for lung cancer as an evidence-based screening method at present, but we all have hopes that—in a few years’ time—we do not need to conclude that this whole idea of trials was an error. Lung cancer continues to be the leading cause of cancer deaths, and a successful strategy to reduce lung cancer mortality is desperately needed.
Although awaiting the final results of the randomized trials, it would certainly be an error not to address the main cause of lung cancer, tobacco smoking. What we know for sure at present is that ignoring or not sufficiently addressing the need for smoking cessation of patients in our lung cancer screening trials and in our daily clinical practice, really would be the unforgivable error. We should avoid it, by using counseling and smoking cessation aids whenever possible.
1. Pedersen JH, Ashraf H, Dirksen A, et al. The Danish randomized lung cancer CT screening trial—overall design and results of the prevalence round. J Thorac Oncol
2. Dirckx JH. Stedman’s Concise Medical dictionary for the Health Professions, 4th ed. Baltimore: Lippincott Williams & Wilkins, 2001.
3. Henschke CI, Yankelevitz DF, Libby DM, et al. Survival of patients with stage I lung cancer detected on CT screening. N Engl J Med
4. Clark KW, Gierada DS, Marquez G, et al. Collecting 48,000 CT exams for the Lung Screening study of the National Lung Screening trial. J Diag Imaging
doi: 10.1007/s10278-008-9145-9, September 2008.
5. Van Iersel CA, De Koning HJ, Draisma G, et al. Risk-based selection from the general population in a screening trial: selection criteria, recruitment and power for the Dutch-Belgian randomised lung cancer Multi-slice CT screening trial (NELSON). Int J Cancer
6. Marshall E. A bruishing battle over lung scans. Science
7. Twombly R. Lung cancer screening debate continues despite international CT study results. J Natl Cancer Inst
8. Pastorino U, Bellomi M, Landoni C, et al. Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results. Lancet
9. Cassidy A, Myles J, van Tongeren M, et al. The LLP risk model: an individual risk prediction model for lung cancer. Br J Cancer
10. Smith RA, Cokkinides V, Brawley OW. Cancer screening in the United States, 2009: A review of current American Cancer Society guidelines and issues in cancer screening. CA Cancer J Clin
11. Bach P, Silvestri GA, Hanger M, Jett JR. Screening for lung cancer. ACCP evidence-based clinical practice guidelines (2nd edition). Chest
12. Nishizawa S, Kojima S, Teramukai S, et al. Prospective evaluation of whole-body cancer screening with multiple modalities including [18
F]Fluorodeoxyglucose positron emission tomography in a healthy population: a preliminary report. J Clin Oncol
doi: 10.1200/JCO.2008.18.223 8, March 2009.