Sixty Years of Lung Cancer Screening: From Sputum Cytology to Low-Dose CT and the Emerging Precision Era

To trace the evolution of lung cancer screening from early radiographic and sputum cytology trials through the landmark randomized trials that established low-dose computed tomography (LDCT) as a guideline-endorsed intervention, and to examine emerging technologies poised to transform the field.

A narrative synthesis of primary trial literature, guideline documents, and emerging research conducted March-May 2026. Key milestones-the Mayo Lung Project, Johns Hopkins Lung Project, Anti-Lung Cancer Association (ALCA) CT trials, Early Lung Cancer Action Project (ELCAP), National Lung Screening Trial (NLST), NELSON trial, and iterative US Preventive Services Task Force (USPSTF) guideline revisions-are reviewed chronologically alongside developments in CT technology and reporting systems.

Early sputum cytology and radiographic trials improved early-stage detection without a mortality benefit. Japanese ALCA trials established LDCT feasibility, demonstrating superior stage distribution (93% vs 53% stage I). The NLST demonstrated a 20% reduction in lung cancer mortality and 6.7% reduction in all-cause mortality with LDCT versus chest radiography, providing the evidence basis for the 2013 USPSTF guidelines. NELSON corroborated these findings, with a 24% lung cancer mortality reduction in men and greater benefit in women. The 2021 USPSTF revision broadened eligibility to ages 50-80 with ≥20 pack-years. Adherence remains suboptimal at 22-55%.

LDCT screening represents a convergence of technological innovation, rigorous clinical investigation, and evolving health policy. Emerging adjuncts, including circulating tumor DNA analysis and AI-assisted image interpretation, may improve detection accuracy and address adherence gaps. Lung-RADS has substantially reduced false-positive rates and continues to evolve.