• Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland.
• Institute of Sport, Exercise and Active Living, Victoria University, Melbourne, Australia.
• Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland3Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins Medicine.
• Information Management Services Inc, Calverton, Maryland.

IMPORTANCE: The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations.

OBJECTIVE: Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations.

DESIGN, SETTING, AND PARTICIPANTS: Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST.

EXPOSURES: Annual CT lung screening for 3 years beginning at age 50 years.

MAIN OUTCOMES AND MEASURES: For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death).

RESULTS: Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (≥1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]).

CONCLUSIONS AND RELEVANCE: Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.