• Department of Radiology, Duke University Medical Center, Durham, North Carolina2Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina.
• Division of Cancer Prevention, National Cancer Institute, Bethesda, Maryland.
• Center for Statistical Sciences, Brown School of Public Health, Providence, Rhode Island5Department of Biostatistics, Brown School of Public Health, Providence, Rhode Island.
• Center for Statistical Sciences, Brown School of Public Health, Providence, Rhode Island.
• Department of Community Health Sciences, Brock University, St Catharines, Ontario, Canada.
• Department of Radiology, Wake Forest University Health Sciences Center, Winston-Salem, North Carolina.
• Department of Radiology, Dartmouth Medical School, Hanover, New Hampshire9Department of Community and Family Medicine, Dartmouth Medical School, Hanover, New Hampshire.
• Department of Radiology, University of California, Los Angeles.

IMPORTANCE: Screening for lung cancer has the potential to reduce mortality, but in addition to detecting aggressive tumors, screening will also detect indolent tumors that otherwise may not cause clinical symptoms. These overdiagnosis cases represent an important potential harm of screening because they incur additional cost, anxiety, and morbidity associated with cancer treatment.

OBJECTIVE: To estimate overdiagnosis in the National Lung Screening Trial (NLST).

DESIGN, SETTING, AND PARTICIPANTS: We used data from the NLST, a randomized trial comparing screening using low-dose computed tomography (LDCT) vs chest radiography (CXR) among 53 452 persons at high risk for lung cancer observed for 6.4 years, to estimate the excess number of lung cancers in the LDCT arm of the NLST compared with the CXR arm.

MAIN OUTCOMES AND MEASURES: We calculated 2 measures of overdiagnosis: the probability that a lung cancer detected by screening with LDCT is an overdiagnosis (PS), defined as the excess lung cancers detected by LDCT divided by all lung cancers detected by screening in the LDCT arm; and the number of cases that were considered overdiagnosis relative to the number of persons needed to screen to prevent 1 death from lung cancer.

RESULTS: During follow-up, 1089 lung cancers were reported in the LDCT arm and 969 in the CXR arm of the NLST. The probability is 18.5% (95% CI, 5.4%-30.6%) that any lung cancer detected by screening with LDCT was an overdiagnosis, 22.5% (95% CI, 9.7%-34.3%) that a non-small cell lung cancer detected by LDCT was an overdiagnosis, and 78.9% (95% CI, 62.2%-93.5%) that a bronchioalveolar lung cancer detected by LDCT was an overdiagnosis. The number of cases of overdiagnosis found among the 320 participants who would need to be screened in the NLST to prevent 1 death from lung cancer was 1.38.

CONCLUSIONS AND RELEVANCE: More than 18% of all lung cancers detected by LDCT in the NLST seem to be indolent, and overdiagnosis should be considered when describing the risks of LDCT screening for lung cancer.