Microsimulation modeling of extended annual CT screening among lung cancer cases in the National Lung Screening Trial

Purpose: To microsimulate the effects of three additional annual CT screening rounds on lung cancer (LC) survival in the National Lung Screening Trial (NLST). Methods: We used multiple imputation to model the effect of additional screening in the full NLST cohort on the time to LC diagnosis and on LC death in those participants who were diagnosed with LC by the end of NLST. Nodule growth models were derived from a Dutch in-vivo study. Microsimulations were repeated 500 times. The method was validated by simulating three rounds of CT screening in the original chest radiography (CXR) cohort. The times up to which the simulations remained within the 95% confidence bands of the CT cohort's original results were used to estimate the validity of the results in the CT cohort with three additional simulated screening rounds. Results: Validation of the simulation approach on the CXR cohort resulted in a LC mortality reduction which remained well within the 95% confidence intervals of the original CT cohort up to 6.5 years after the start of simulations. Simulating additional CT screening in the CT cohort led to LCs being diagnosed earlier than originally, resulting in a relative risk reduction in LC mortality of 11% (95% confidence bands, 7% to 14%) at 6.5 years. This is equivalent to preventing 71% (48% to 94%) more LC deaths than the original CT cohort achieved in comparison to the original CXR cohort. Conclusion: Three additional annual CT screening rounds in the NLST may have led to substantial further LC mortality reduction.