Estimating heterogeneous survival treatment effects of lung cancer screening approaches: A causal machine learning analysis

The National Lung Screening Trial (NLST) found that low-dose computed tomography (LDCT) screening provided lung cancer (LC) mortality benefit compared to chest radiography (CXR). Considerable research concerns identifying the differential treatment effects that may exist in certain subpopulations. We shed light on several important issues in existing research and highlight the need for further investigation of the heterogeneous comparative effect of LDCT versus CXR, using more flexible and rigorous statistical approaches. We used a high-performance Bayesian machine learning approach designed for censored survival data, accelerated failure time Bayesian additive regression trees model (AFT-BART), to flexibly capture the relationships between the failure time and predictors. We then used the counterfactual framework to draw Markov chain Monte Carlo samples of the individual treatment effect for each participant. Using these posterior samples, we explored the possible treatment effect heterogeneity via a stepwise binary tree approach. When re-analyzed with AFT-BART, LDCT did not have a statistically significant LC or overall mortality benefit compared to CXR. The Asian and Black (particularly those with pack-year ≥ 37 years and without emphysema) NLST population were shown to have enhanced overall mortality benefit from LDCT than the population average. Although inconclusive for LC mortality benefit, Asians, Blacks and Whites with history of chronic obstructive pulmonary disease showed a small trend towards benefit from LDCT. Causal inference with flexible machine learning modeling can provide valuable knowledge for informing treatment decision and planning targeted clinical trials emphasizing personalized medicine approaches.