Imaging-based biological age estimation predicts competing mortality risk in lung cancer screening

Abstract

Abstract Lung cancer screening (LCS) participants have a high competing risk of non-lung cancer related death, which limits screening benefit. We hypothesized that imaging-based biological age can identify individuals at higher risk of non-lung cancer mortality. Low dose computed tomography scans from a large LCS trial were retrospectively analyzed. Bone density loss, muscular fat infiltration, vascular calcification, and visceral fat mass were calculated using segmentations from a nnU-Net based deep learning segmentation model. Each participant’s age gap, defined as the difference between their estimated biological age and chronological age, was estimated with disease course mapping using a Bayesian mixed-effects model. Disease course map construction used all available longitudinal scan data, whilst individual biological age prediction used baseline scan data only. The performance of age gap as a parameter in competing risk models for non-lung cancer related death versus lung cancer diagnosis was evaluated, following the TRIPOD + AI reporting guideline. We included 29,745 scans from 12,478 participants in the final analysis. Median follow-up was 5 years, representing 58,284 person-years at risk. Multivariable survival models of competing risks were constructed, including the estimated age gap. The subdistribution hazard ratio (sHR) for each decade of age gap for non-lung cancer related death was higher (sHR = 2.0, 95% CI 1.8–2.3), compared to lung cancer diagnosis (sHR = 1.3, 95% CI 1.2–1.5). Addition of age gap improved model concordance of non-lung cancer death compared to a model with clinical variables alone (pooled C-index = 0.69 vs 0.73, difference + 0.04, 95% CI 0.03–0.04, p < 0.001). Biological age estimation using an imaging-based disease progression model improves prediction of non-lung cancer related death in lung cancer screening.