• Department of Radiology, The University of North Carolina, Chapel Hill, NC, USA.
• The University of North Carolina Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA.

The benefits and harms of lung cancer screening reported in the National Lung Screening Trial (NLST) likely differ from those observed in academic and community settings. High rates of positive screening findings in the NLST led to the development of the Lung CT Screening Reporting and Data System (Lung-RADS) to standardize interpretation and reporting. We conducted a prospective observational study of lung cancer screening data from four lung cancer screening sites in North Carolina to compare prospective use of Lung-RADS in a real-world screened population versus Lung-RADS retrospectively applied to the NLST, and to determine if Lung-RADS assessment use differs in academic versus community settings. We included 4,037 screening examinations from 11/2014 to 12/2018 in academic and community sites and 75,126 NLST LDCT screening exams. On baseline screening exams, the proportion of positive LDCT exams was higher in community versus academic sites or the NLST (17.7% vs. 11.4% and 13.6%, P value <0.01). On subsequent screens, the proportion of positive exams was lowest in the NLST and higher in community and academic sites (5.9% vs. 12.7% and 11.6%, P value <0.01). After adjusting for age, race, sex, and smoking status, patients screened at academic versus community sites were 34% less likely to have a positive screen at baseline [adjusted odds ratio (aOR) =0.66; 95% confidence interval (95% CI): 0.51-0.86] but on subsequent examinations, there was no difference in academic versus community sites (aOR =0.91; 95% CI: 0.58-1.43). Our findings may be due to differences in radiologists' training or experiences or the availability of prior images for comparison.