Lead-time bias in esophageal cancer screening in high-risk areas in China

OBJECTIVE: To investigate what extent lead-time bias is likely to affect endoscopic screening effectiveness for esophageal cancer in the high-risk area in China. METHODS: A screening model based on the epidemiological cancer registry data, yielding a population-level incidence and mortality rates, was carried out to simulate study participants in the high-risk area in China, and investigate the effect of lead-time bias on endoscopic screening with control for length bias. RESULTS: Of 100,000 participants, 6,150 (6.15%) were diagnosed with esophageal squamous dysplasia during the 20-year follow-up period. The estimated lead time ranged from 1.67 to 5.78 years, with a median time of 4.62 years [interquartile range (IQR): 4.07−5.11 years] in the high-risk area in China. Lead-time bias exaggerated screening effectiveness severely, causing more than a 10% overestimation in 5-year cause-specific survival rate and around a 43% reduction in cause-specific hazard ratio. The magnitude of lead-time bias on endoscopic screening for esophageal cancer varied depending on the screening strategies, in which an inverted U-shaped and U-shaped effects were observed in the 5-year cause-specific survival rate and cause-specific hazard ratio respectively concerning a range of ages for primary screening. CONCLUSIONS: Lead-time bias, usually causing an overestimation of screening effectiveness, is an elementary and fundamental issue in cancer screening. Quantification and correction of lead-time bias are essential when evaluating the effectiveness of endoscopic screening in the high-risk area in China.