Diagnostic Performance of the AptoDetect™-Lung Biomarker for Lung Cancer in a High-Risk Korean Population: A Multicenter Prospective Study

Background/Objectives: Blood-based biomarkers may improve risk stratification of indeterminate pulmonary nodules detected on low-dose computed tomography (LDCT). We evaluated the diagnostic performance and independent predictive value of an aptamer-based blood assay, AptoDetect™-Lung, in a high-risk Korean screening population. Methods: This multicenter prospective cohort study enrolled adults with Lung Imaging Reporting and Data System (Lung-RADS) category 3 or 4 pulmonary nodules identified on LDCT across ten tertiary hospitals in South Korea between June 2023 and December 2024. Analyses focused on a predefined high-risk subgroup meeting Korean screening criteria (age 54–74 years and ≥30 pack-years of smoking). Baseline serum AptoDetect™-Lung scores were measured. Associations with lung cancer diagnosis were assessed using univariate and multivariable logistic regression, adjusting for clinical and radiologic variables. Diagnostic performance was evaluated using receiver operating characteristic analysis. Results: Among 1084 participants with histopathologic confirmation, 319 met high-risk criteria, of whom 260 (81.5%) were diagnosed with lung cancer. In this subgroup, the AptoDetect™-Lung score was independently associated with malignancy after adjustment (adjusted odds ratio of 1.14 per unit; 95% confidence interval of 1.02–1.27; p = 0.020). Discriminative performance was higher in the high-risk subgroup than in the overall cohort (area under the curve [AUC] of 0.639 vs. 0.570; p = 0.025). Performance was higher for squamous cell carcinoma and small-cell lung cancer than for adenocarcinoma. A multivariable model incorporating biomarker score, Lung-RADS category, age, and family history achieved an AUC of 0.710. Conclusions: An aptamer-based blood biomarker may provide modest adjunctive value for risk stratification in high-risk individuals.