Study Highlights: The NLST trial found that three rounds of low-dose CT scans (T0, T1, and T2) resulted in a 20% relative reduction in lung cancer mortality compared with radiography; low-dose CT scans had higher sensitivity for early-stage lung cancer, but lower positive predictive value than radiography; two rounds of lung cancer incidence screening using low-dose CT scans resulted in a decrease in the number of late-stage lung cancer diagnoses compared with radiography decreasing numbers and increasing numbers of early-stage lung cancer diagnoses. The U.S. National Lung Screening Trial was designed to determine whether three rounds of annual low-dose computed tomography (LDCT) screening (T0, T1, and T2) compared with chest radiography reduced lung cancer mortality. In this paper, Dr. Aberle et al. of the University of California Radiological Sciences Research Unit present detailed data from the first two rounds of lung cancer incidence screening (T1 and T2). The paper was published in the September 2013 online edition of the leading international journal NEJM. The investigators assessed subjects’ screening adherence rates, screening and downstream diagnostic test results, lung cancer case characteristics, and first-line treatment, in addition to examining the performance characteristics of the two screening methods. The results showed that in the T1 and T2 screening, subjects in the low-dose CT group had positive rates of 27.9% and 16.8%, respectively, compared with 6.2% and 5.0% in the radiography group. In the low-dose CT group, the sensitivity and specificity of T1 screening were 94.4% and 72.6%, respectively, with a positive predictive value of 2.4% and a negative predictive value of 99.9%; the positive predictive value of T2 screening was 5.2%. In the radiographic group, the sensitivity of T1 screening was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8%; the sensitivity and positive predictive value increased in T2 screening. For patients with known stage of lung cancer, 87 (47.5%) of the T1 scans in the low-dose CT scan group were stage IA and 57 (31.1%) were stage III or IV, while 31 (23.5%) of the T1 scans in the radiography group were stage IA and 78 (59.1%) were stage III or IV. The same group differences in stage distribution were found in T2 screening. The study thus concluded that low-dose CT scans have a higher sensitivity for detecting early lung cancer, but a lower positive predictive value than radiography. Two rounds of lung cancer incidence screening using low-dose CT scans resulted in a lower number of advanced lung cancer diagnoses and an increased number of early lung cancer diagnoses compared to radiography. Background: The National Lung Screening Trial (NLST) is a randomized trial comparing lung cancer-specific mortality in a high-risk cohort of people with low-dose CT scans versus chest X-ray screening.The NLST trial found that three rounds of low-dose CT scans (T0, T1, and T2) resulted in a 20% relative reduction in lung cancer mortality compared with radiography.