Transporting Lung Cancer Screening Effects From National Lung Screening Trial to a US Screening-Eligible Population

The National Lung Screening Trial (NLST) found that screening with annual low-dose computed tomography (LDCT) reduces lung cancer (LC) mortality. Because studies have shown that the US population eligible for screening differs from NLST, we sought to quantitatively extend the NLST findings to this population.

We reweighted individual-level NLST data using inverse odds weights (IOW) to the covariate distribution of a contemporary screening-eligible population from the 2022 Behavioral Risk Factor Surveillance System (BRFSS) data. In the IOW and unweighted NLST population, we estimated the LC-specific and all-cause mortality among individuals undergoing three annual screenings of LDCT compared with chest radiography, as well as false-positive rates in the LDCT arm only.

We included 53,454 NLST participants and 7,265,314 survey-weighted screening-eligible BRFSS respondents (unweighted sample of 15,779). The BRFSS population was older, more racially and ethnically diverse, and more likely to currently smoke and have respiratory comorbidities. We estimated similar benefits of screening on LC and all-cause mortality in the weighted versus unweighted NLST population (5-year LC risk difference [RD; 95% CI], -29 [-54, 4] v -23 [-44, 3]; all-cause RD [95% CI], -44 [-95, 8] v -37 [-66, -7] deaths per 10,000 screened). Estimated false-positive rates were higher in the weighted versus unweighted NLST population across three annual screenings.

We estimated similar mortality benefits and slightly increased false-positive rates from LDCT in the weighted versus unweighted NLST population. Our findings account for the potential differences within subgroups of interest but not variations in longitudinal adherence and diagnostic work-up between trial and clinical practice.