A Cost-Effectiveness Analysis of Lung Cancer Screening With Low-Dose Computed Tomography and a Diagnostic Biomarker

JNCI Cancer Spectr. 2021 Oct 6;5(6):pkab081. doi: 10.1093/jncics/pkab081. eCollection 2021 Dec.


Background: The Lung Computed Tomography Screening Reporting and Data System (Lung-RADS) reduces the false-positive rate of lung cancer screening but introduces prolonged periods of uncertainty for indeterminate findings. We assess the cost-effectiveness of a screening program that assesses indeterminate findings earlier via a hypothetical diagnostic biomarker introduced in place of Lung-RADS 3 and 4A guidelines.

Methods: We evaluated the performance of the US Preventive Services Task Force (USPSTF) recommendations on lung cancer screening with and without a hypothetical noninvasive diagnostic biomarker using a validated microsimulation model. The diagnostic biomarker assesses the malignancy of indeterminate nodules, replacing Lung-RADS 3 and 4A guidelines, and is characterized by a varying sensitivity profile that depends on nodules' size, specificity, and cost. We tested the robustness of our findings through univariate sensitivity analyses.

Results: A lung cancer screening program per the USPSTF guidelines that incorporates a diagnostic biomarker with at least medium sensitivity profile and 90% specificity, that costs $250 or less, is cost-effective with an incremental cost-effectiveness ratio lower than $100 000 per quality-adjusted life year, and improves lung cancer-specific mortality reduction while requiring fewer screening exams than the USPSTF guidelines with Lung-RADS. A screening program with a biomarker costing $750 or more is not cost-effective. The health benefits accrued and costs associated with the screening program are sensitive to the disutility of indeterminate findings and specificity of the biomarker, respectively.

Conclusions: Lung cancer screening that incorporates a diagnostic biomarker, in place of Lung-RADS 3 and 4A guidelines, could improve the cost-effectiveness of the screening program and warrants further investigation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Advisory Committees
  • Analysis of Variance
  • Biomarkers, Tumor / economics*
  • Cost-Benefit Analysis
  • Humans
  • Lung Neoplasms / diagnostic imaging*
  • Lung Neoplasms / prevention & control
  • Practice Guidelines as Topic
  • Program Evaluation
  • Quality-Adjusted Life Years
  • Radiation Dosage
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed / economics*
  • Tomography, X-Ray Computed / methods
  • Uncertainty
  • United States


  • Biomarkers, Tumor