The extraordinarily long lead times of screen-detected lung cancer in never-smokers

BackgroundThe randomized trials of low-dose computed tomography (LDCT) screening enrolled individuals at high risk of lung cancer: heavy cigarette smokers. Nevertheless, opportunistic screening of never smokers has become commonplace in certain regions of East Asia. Lung cancer detection rates reported for this low risk group regularly exceed those reported in the randomized trials. We sought to determine the lead time - the length of time between screen detection and when symptoms would manifest (clinical presentation) - associated with LDCT detection rates reported in Taiwan. ObjectiveTo estimate the lead time for LDCT lung cancer detection in never smoking Taiwanese females, under the assumption that all detected cancers progress. MethodsWe analyzed data from the Taiwan Lung Cancer Screening in Never-Smoker Trial (TALENT), a prospective cohort of {approx}12000 never smokers aged 55-75, and compared age-specific screen detection rates to lung cancer incidence rates in the pre-screening period. Lead time was estimated using Morrisons approximation: one-half the ratio of screen detection to pre-screening incidence. ResultsInvasive lung cancer detection rates in never smoking females were 18 (age 70-74) to 37 (age 55-59) times higher than the respective age-specific lung cancer incidence rates prior to widespread screening. The estimated lead times for invasive lung cancers thus ranged from 9 (age 70-74) to 18.5 years (age 55-59). Had we included in situ lung cancer detection, the estimated lead time of screening would range from approximately 10 to 20 years. ConclusionIf all detected cancers progress, the lead times for LDCT lung cancer detection in never-smokers would be 5 to 20 times longer than that reported in the randomized trials of heavy smokers (1 to 2 years). Such extended lead times are not only undesirable (Why label and treat a patient for a cancer not destined to clinically present in the next 1 or 2 decades?), but also a major source of overdiagnosis - providing plenty of time for a patient to die from other causes before developing a symptomatic cancer (Type 1 overdiagnosis). Furthermore, some screen-detected cancers may not progress and thus have an infinite lead time (Type 2 overdiagnosis). Regardless, it appears that substantial overdiagnosis has occurred in screening low-risk, never smoking individuals.