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

RATIONAL AND

Objectives

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.

Materials And Methods

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.

Results

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%.

Conclusion

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.