Estimation of Lead Time via Low-Dose CT in the National Lung Screening Trial

Based on recent reports from the National Lung Screening Trial (NLST), smokers who were screened by low-dose computer tomography (LDCT) had a 20% lower chance of dying from lung cancer than those screened by chest X-rays. However, due to the complexities of lead time bias and over diagnosis, no formal test has been shown to reduce lung cancer mortality. To correctly evaluate survival benefit due to early detection, it is critical to estimate lead time, the length of time that detection of a disease is advanced by screening. We applied a recently developed probability method to estimate lead time, using the LDCT data from NLST, where human lifetime was treated as random and derived from the actuarial life table of the US Social Security Administration. Using Bayesian posterior samples of key parameters extracted from the NLST-LDCT data, simulations on lead time were carried out on 16 hypothetical cohorts with four initial ages (55, 60, 65, and 70) and four future screening intervals (12, 18, 24, and 30 months). For each scenario, the estimated lead time for both screen-detected and interval cases is reported. Results show that the probability of no-early-detection (interval cases) increases monotonically when the screening interval increases for both genders. A male heavy smoker with an initial screening age at 60 has 11.65% (female 6.76%) chance of no-early-detection with annual screenings. This probability increases to 36.35% (female 28.26%) if the screenings were biennial. The mean lead time appears longer for women than for men. The mean lead time decreases when the screening interval increases, but it appears stable across different initial age groups. These results lay a foundation to evaluate survival benefit accurately with LDCT and to schedule future screening exams.