Abstract C124: An effective and affordable blood test for lung cancer early detection using four protein markers and artificial intelligence

Abstract Background: Lung cancer is the leading cause of cancer incidence and mortality worldwide. While low-dose computed tomography (LDCT) reduces mortality in high-risk populations, its high false-positive rate and the required specialized infrastructure and radiologists limit its application. This study assesses LungCanSeek, a novel blood-based protein test for lung cancer early detection. Methods: This retrospective study enrolled 1,814 participants (1,095 lung cancer, 719 non-cancer) from three independent cohorts. Blood samples were analyzed for four protein tumor markers (PTMs) using Roche cobas. Artificial intelligence (AI) algorithms were developed for lung cancer detection and subtype classification: lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), and small cell lung cancer (SCLC). A two-step lung cancer screening approach was modeled, using LungCanSeek for initial screening, followed by LDCT for LungCanSeek's positive cases. Results: LungCanSeek demonstrated 83.5% sensitivity, 90.3% specificity, and 86.2% accuracy overall. Sensitivities of LUAD, LUSC, and SCLC were 83.3%, 81.4%, and 91.9%. Sensitivity increased with clinical stage in non-small cell lung cancer (NSCLC): 59.5% (I), 69.8% (II), 86.5% (III), and 91.3% (IV). For limited- and extensive-stage SCLC, sensitivities were 91.3% and 93.0%. The subtype classification accuracy was 77.4%. Compared with other blood-based lung cancer early detection tests like OncImmune’s EarlyCDT-Lung (41.0% sensitivity, 91.0% specificity) and DELFI’s FirstLook-Lung (84.0% sensitivity, 50.9% specificity), LungCanSeek showed superior performance. A screening was modeled for 9 million high-risk adults, based on the number of 15 million eligible individuals in the USA in 2024 at a 60% rate, with a 2.5% lung cancer incidence. LungCanSeek reduced false positives by 2.4-fold to 851,175 compared to 2,062,125 with LDCT. The two-step approach further cut false positives by 10.3-fold to just 200,026. LDCT’s total cost was $2,493 million, exceeding LungCanSeek’s $720 million and two-step’s $996.5 million. Conclusions: LungCanSeek is a non-invasive, easy to perform, cost-effective (reagent cost $15) and robust test for lung cancer early detection. The two-step approach offers a cost-effective strategy for population-wide lung cancer screening. Citation Format: Mao Mao, Wei Bing, Wang Wen. jian, Geng Shuai. peng, Wu Wei, Ding Chen. yu, Zhu Dan. dan, Cheng Shuo. yao, Zhao Qiu. rong, Luan Yi, Li Shi. yong. An effective and affordable blood test for lung cancer early detection using four protein markers and artificial intelligence [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C124.