• Division of Pulmonary and Critical Care Medicine, Department of Medicine, Rochester University Medical Center, Rochester, NY; Wilmot Cancer Institute, University of Rochester, Rochester, NY. Electronic address: patricia_rivera@urmc.rochester.edu.
• Department of Radiology, The University of North Carolina, Chapel Hill, NC.
• Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC; Department of Epidemiology, The University of North Carolina, Chapel Hill, NC.
• Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC; Department of Medicine, The University of North Carolina, Chapel Hill, NC.
• Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Washington DC.
• Department of Radiology, The University of North Carolina, Chapel Hill, NC; Lineberger Comprehensive Cancer Center, The University of North Carolina, Chapel Hill, NC.

BACKGROUND: Trial participants are typically healthier than the general population. Differences in underlying characteristics between the population undergoing lung cancer screening (LCS) and LCS trial participants may alter the benefits of LCS.

RESEARCH QUESTION: Does the risk of developing and dying from lung cancer differ between trial participants and the general population?

STUDY DESIGN AND METHODS: Using data from the i) North Carolina Lung Screening Registry (NCLSR), ii) 2022 Center for Disease Control and Prevention's Behavioral Risk Factor Surveillance System (BRFSS) Lung Cancer Screening Module, and iii) National Lung Screening Trial (NLST), we estimated the 5-year probability of developing and dying from lung cancer if not screened using publicly available macros. Using Cohen's D, we compared these metrics in NCLSR and BRFSS populations to NLST participants.

RESULTS: BRFSS and NCLSR populations were older, had higher rates of COPD and prior history of cancer, and higher risk of developing and dying from lung cancer compared with NLST participants. While NCLSR populations were more likely to be currently smoking, median smoking exposure was similar among all groups. Median 5-year lung cancer risk was 21.2/1000 (IQR:13.0-35.2) among NLST participants compared with 46.1/1000 among 2013 BRFSS (Cohen=0.67515), 34.5/1000 among 2021 BRFSS (Cohen=0.47813), 36.5/1000 among 2013 NCLSR (Cohen=0.07748), and 32.3/1000 among 2021 NCLSR (Cohen=0.48289) populations. Median 5-year probability of dying from lung cancer if not screened showed similar patterns, with lowest rates among NLST participants at 12.5/1000 versus BRFSS and NCLSR populations.

INTERPRETATION: NCLSR and BRFSS populations have similar smoking exposure as NLST participants, but higher prevalence of lung cancer risk factors, lung cancer risk scores, and risk of lung cancer death if not screened. Monitoring LCS in the population is crucial, as individuals are older and have more comorbidities, raising concerns about potential LCS harms. However, they have a higher risk of dying from lung cancer if not screened.