Low-Dose CT Screening for Lung Cancer: Trial and Error?

Abstract

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