ArticlesDetection of lung cancer through low-dose CT screening (NELSON): a prespecified analysis of screening test performance and interval cancers
Introduction
Until the 1990s, no effective screening test for lung cancer was available. Screening studies using sputum cytology or chest radiography did not show a significant reduction in lung cancer mortality. In the 1990s, cohort studies using low-dose CT as a lung cancer screening test were initiated.1, 2, 3 Low-dose CT seemed to be able to detect more and smaller lung cancers than chest radiography, with most being diagnosed at stage I.4, 5, 6 Moreover, survival in patients with screen-detected lung cancer was impressive. Findings from the National Lung Screening Trial (NLST) showed a 20% reduction in lung cancer mortality using low-dose CT compared with screening using chest radiography.7 The CISNET lung cancer working group modelled and assessed hundreds of screening scenarios using data from NLST; 26 selected efficient screening scenarios led to reductions in lung cancer mortality of between 4·6% and 21·2%.8 As a result, the US Preventive Services Task Force and medical societies recommended annual low-dose CT screening in the USA for people at high risk of developing lung cancer.8, 9, 10 However, no reduction in lung cancer mortality with an annual low-dose CT screening strategy has been reported in three smaller European trials,11, 12, 13 and results of several larger European trials are still awaited. In many European countries, the outcome of the NELSON trial or pooled analyses is awaited before a decision about implementation of a national service lung cancer screening programme is made.
Efficacy and acceptance of low-dose CT screening for lung cancer depends on the sensitivity of the screening test (ie, the risk of not detecting a lung cancer through screening). Lung cancers not detected by screening but diagnosed during the screening interval, known as interval cancers, might have been missed at screening or might have developed between screening and detection. Few studies about the incidence and characteristics of interval cancers in lung cancer screening have been reported.11, 14, 15, 16 None of these studies assessed causes of interval cancers, or whether improvements to the screening algorithm were possible.
The NELSON trial is a randomised trial to assess whether low-dose CT screening with an increasing length of screening interval (1, 2, and 2·5 years) compared with no screening reduces lung cancer mortality.17, 18 In this prespecified analysis, we aimed to assess the performance of the screening test to detect interval cancers, and provide insights into the incidence, histopathology, and causes for failed detection of these cancers.
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Study design and participants
Individuals from four centres in the Netherlands and Belgium were enrolled and randomly assigned to receive low-dose CT screening or no screening. Eligible participants were adults aged 50–75 years, who had smoked 15 or more cigarettes per day for more than 25 years or ten or more cigarettes per day for more than 30 years, and were still smoking or had stopped smoking less than 10 years previously. People with self-reported moderate or bad health (first question of SF-36), inability to climb
Results
Between Dec 23, 2003, and July 6, 2006, 15 822 individuals from four centres in the Netherlands and Belgium were enrolled and randomly assigned to receive low-dose CT screening (n=7915) or no screening (n=7907). For this prespecified analysis, we excluded the 7907 participants randomly assigned to the no screening group, the 477 participants from Belgium (because no data were yet available from the Belgian cancer registry), and 283 participants who did not attend their screening examinations
Discussion
In this study, we assessed the epidemiological, radiological, and clinical characteristics of screen-detected and interval lung cancers in the NELSON trial. 187 (3%) of the 7155 participants studied were diagnosed with lung cancer detected by screening, and another 34 (<1%) participants were diagnosed with interval lung cancer. Overall, sensitivity was about 85%, specificity about 99%, positive predictive value about 40%, and negative predictive value greater than 99%. Retrospectively, about a
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