Over- and underscreening for lung cancer.

Background and Objective: While low-dose computed tomography (LDCT) has significantly reduced lung cancer mortality, its full potential remains constrained under current screening paradigms. This review evaluates clinical discrepancies in LDCT implementation and explores adaptive screening frameworks. Methods: We synthesized clinical screening outcomes and investigated tumor natural history to identify the drivers of observed misalignments, providing the rationale for optimized screening strategies. Key Content and Findings: Evidence highlights significant disparities between Western and Eastern cohorts, with East Asian initiatives identifying a much higher proportion of early-stage disease driven by ground-glass nodules (GGNs) in non-smokers. These discrepancies are rooted in the diverse evolutionary trajectories of lung cancer, ranging from indolent GGNs with protracted natural history to aggressive subtypes with narrow "curative time windows". The mismatch between conventional smoking-centric protocols and these biological realities leads to a screening paradox: overscreening, which involves excessive screening frequency beyond clinical necessity primarily among low-risk individuals (e.g., annually) but also occurring within high-risk groups, and the intensive follow-up of indolent or clinically insignificant lesions, coexists with underscreening, which encompasses the failure to reach high-risk populations, the lack of adequate coverage for traditionally low-risk individuals, and the oversight of aggressive early lesions. To provide a conceptual basis for potentially reconciling these misalignments, we explore the "curative time window" theory and a hypothesis-generating "low-age, low-frequency" strategy. This framework considers the rationale for earlier baseline screening to intercept aggressive, early-onset cases while potentially extending intervals for individuals with negative baseline results or indolent trajectories to optimize resource allocation. Conclusions: Current smoking-centric guidelines may lack the flexibility to accommodate the biological diversity and shifting epidemiology of lung cancer. A transition toward risk-adapted screening frameworks, such as the conceptual "low-age, low-frequency" strategy, is suggested as a potential approach to optimize curative outcomes and screening efficiency, though prospective validation remains warranted.