Better evidence about screening for lung cancer.

In October 2010, the National Cancer Institute (NCI) announced that patients who were randomly assigned to screening with low-dose computed tomography (CT) had fewer deaths from lung cancer than did patients randomly assigned to screening with chest radiography. The first report of the NCI-sponsored National Lung Screening Trial (NLST) in a peer-reviewed medical journal appears in this issue of the Journal.1 Eligible participants were between 55 and 74 years of age and had a history of heavy smoking. They were screened once a year for 3 years and were then followed for 3.5 additional years with no screening. At each round of screening, results suggestive of lung cancer were nearly three times as common in participants assigned to low-dose CT as in those assigned to radiography, but only 2 to 7% of these suspicious results proved to be lung cancer. Invasive diagnostic procedures were few, suggesting that diagnostic CT and comparison with prior images usually sufficed to rule out lung cancer in participants with suspicious screening findings. Diagnoses of lung cancer after the screening period had ended were more common among participants who had been assigned to screening with chest radiography than among those who had been assigned to screening with low-dose CT, suggesting that radiography missed cancers during the screening period. Cancers discovered after a positive low-dose CT screening test were more likely to be early stage and less likely to be late stage than were those discovered after chest radiography. There were 247 deaths from lung cancer per 100,000 person-years of follow-up after screening with low-dose CT and 309 per 100,000 person-years after screening with chest radiography. The conduct of the study left a little room for concern that systematic differences between the two study groups could have affected the results (internal validity). The groups had similar characteristics at baseline, and only 3% of the participants in the low-dose CT group and 4% in the radiography group were lost to follow-up. However, there were two systematic differences in adherence to the study protocol. First, as shown in Figure 1 of the article, although adherence to each screening was 90% or greater in each group, it was 3 percentage points lower for the second and third radiography screenings than for the corresponding low-dose CT screenings. Because more participants in the radiography group missed one or two screenings, the radiography group had more time in which a lung cancer could metastasize before it was detected. Second, participants in the low-dose CT group were much less likely than those in the radiography group to have a diagnostic workup after a positive result in the second and third round of screening (Table 3 of the article), which might have led to fewer screening-related diagnoses of early-stage lung cancer after low-dose CT. The potential effect of these two differences in study conduct seems to be too small to nullify the large effect of low-dose CT screening on lung-cancer mortality. The applicability of the results to typical practice (external validity) is mixed. Diagnostic workup and treatment did take place in the community. However, the images were interpreted by radiologists at the screening center, who had extra training in the interpretation of low-dose CT scans and presumably a heavy low-dose CT workload. Moreover, trial participants were younger and had a higher level of education than a ran-