Abstract
Lung cancer remains the leading cause of cancer-related deaths worldwide, partly because many patients are diagnosed at late stages, highlighting the urgent need for effective early detection and intervention strategies. Low-dose computed tomography (LDCT)-based screening reduces lung cancer mortality in high-risk populations defined by age and smoking history; however, the uptake of LDCT remains low among eligible individuals. Compounding this issue, modelling studies estimate that nearly half of lung cancers occur in individuals who do not meet eligibility criteria for LDCT-based lung cancer screening under current guidelines. Moreover, LDCT-based screening has inherent limitations, including a high rate of false-positive results that can lead to unnecessary invasive procedures, as well as substantial costs that limit scalability. Major efforts have been made to identify novel biomarkers such as radiomic features and liquid biopsy assays to enhance the accuracy of lung cancer risk prediction. Furthermore, the increasing detection of pulmonary nodules by LDCT or diagnostic CT scans has highlighted the importance of therapeutic interventions that can enable interception of high-risk precancerous nodules and halt their progression to invasive disease. In this Review, we summarize the current state of lung cancer screening, the disparities and infrastructural considerations for optimal implementation, and future directions in the development of biomarkers and design of precancer interception strategies that could transform both lung cancer prevention and early intervention.