In a 2008 systematic review of chest CT lung cancer screening studies, the mean proportion of patients with any incidental abnormality was 65.2% (95% confidence interval [CI], 63.5%–66.9%). The mean proportion of patients with clinically significant incidental findings—defined as any abnormality considered to require additional diagnostic workup—was 14.2% (95% CI, 13.2%–15.2%). It is not clear whether the detection of these abnormalities produces a net benefit or a net harm.
A less familiar harm is overdiagnosis, the diagnosis of a condition that would not have become clinically significant had it not been detected by screening. In the case of screening with LDCT, overdiagnosis could lead to unnecessary diagnosis of lung cancer requiring some combination of surgery (e.g., lobectomy), chemotherapy, and radiation therapy. Although overdiagnosis is almost impossible to document in a living individual, autopsy studies suggest that many individuals die with lung cancer rather than from it. In one study, about one-sixth of all lung cancers found at autopsy had not been clinically recognized before death. Even this may be an underestimate because autopsy probably fails to detect many small lung cancers that are detectable by CT. Studies in Japan provide additional evidence that screening with LDCT could lead to a substantial amount of overdiagnosis. In a study in which smokers and nonsmokers were annually screened for lung cancer between 1996 and 1998 using LDCT, the overall rate of screen-detected lung cancers was very similar in the two groups: 0.46% for smokers (mainly men) and 0.41% for nonsmokers (mainly women). The nonsmoking group may have included individuals who were at an elevated risk for lung cancers for other reasons, but no information is provided on this point. A second study involving both smokers and nonsmokers reported a similar finding of a 1.1% lung cancer detection rate in both groups. Confirmative studies are needed to establish the level of overdiagnosis that might be associated with CT screening for lung cancer. In that same population, the volume-doubling times of 61 lung cancers were estimated using an exponential model and successive CT images. Lesions were classified into three types: (1) type G (ground glass opacity), (2) type GS (focal glass opacity with a solid central component), and (3) type S (solid nodule). The mean-doubling times were 813 days, 457 days, and 149 days for types G, GS, and S, respectively. In this study, annual CT screening identified a large number of slowly growing adenocarcinomas that were not visible on chest x-ray.
With completion of the NLST, there is now evidence that screening with LDCT can reduce lung cancer mortality risk in ever-smokers who have smoked 30 pack-years or more. The NLST included 33 centers across the United States. Eligible participants were between the ages of 55 years and 74 years at the time of randomization, had a history of at least 30 pack-years of cigarette smoking, and, if former smokers, had quit within the past 15 years. A total of 53,454 persons were enrolled; 26,722 persons were randomly assigned to screening with LDCT and 26,732 persons were randomly assigned to screening with chest x-ray. Any noncalcified nodule found on LDCT measuring at least 4 mm in any diameter and x-ray images with any noncalcified nodule or mass were classified as positive, although radiologists had the option of not calling a final screen positive if a noncalcified nodule had been stable on the three screening exams. The LDCT group had a substantially higher rate of positive screening tests than did the radiography group (round 1, 27.3% vs. 9.2%; round 2, 27.9% vs. 6.2%; and round 3, 16.8% vs. 5.0%). Overall, 39.1% of participants in the LDCT group and 16.0% in the radiography group had at least one positive screening result. Of those who screened positive, the false-positive rate was 96.4% in the LDCT group and 94.5% in the chest radiography group. This was consistent across all three rounds.