Lung Cancer Detectability by Test, Histology, Stage, and Gender: Estimates from the NLST and the PLCO Trials

BACKGROUND: Implementing optimal lung cancer screening programs requires knowledge of the natural history and detectability of lung cancer. This information can be derived from the results of clinical trials with the aid of microsimulation models. METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) program and individual-level data from the National Lung Screening Trial (NLST) and the Prostate, Lung, Colon, and Ovarian Cancer Screening trial (PLCO) were used to investigate the sensitivity (by histology and stage) of CT and chest radiography (CXR) and the mean preclinical sojourn time (MPST) of lung cancer (by gender, histology, and stage). The MISCAN-Lung model was used to reproduce the lung cancer incidence by method of detection (clinically or screen-detected), gender, histology, and stage in both trials and SEER, by calibrating CT and CXR sensitivity and natural history parameters. RESULTS: CT sensitivity ranges from 8.83% to 99.35% and CXR sensitivity from 2.51% to 97.31%, depending on histology and stage. CT sensitivity for stage IA is more than 3-fold higher compared with CXR, for all histologies. The total MPST estimates for lung cancer progressing through preclinical stages IA to IV range from 3.09 to 5.32 years for men and 3.35 to 6.01 years for women. The largest difference in total MPST between genders was estimated for adenocarcinoma. CONCLUSIONS: We estimate longer MPSTs for lung cancer compared with previous research, suggesting a greater window of opportunity for lung cancer screening. IMPACT: This study provides detailed insights into the natural history of lung cancer and CT screening effectiveness.