Abstract
BACKGROUND: Although low dose computed tomography (LDCT)-based lung cancer screening (LCS) can decrease lung cancer-related mortality among high-risk individuals, it remains an imperfect and substantially underutilized process. LDCT-based LCS may result in false-positive findings, which can lead to invasive procedures and potential morbidity. Conversely, current guidelines may fail to capture at-risk individuals, particularly those from under-represented minority populations. To address these limitations, numerous biomarkers have emerged to complement LDCT and improve early lung cancer detection. CONTENT: This review focuses primarily on blood-based biomarkers, including protein, microRNAs, circulating DNA, and methylated DNA panels, in current clinical development for LCS. We also examine other emerging biomarkers-utilizing airway epithelia, exhaled breath, sputum, and urine-under investigation. We highlight challenges and limitations of biomarker testing, as well as recent strategies to integrate molecular strategies with imaging technologies. SUMMARY: Multiple biomarkers are under active investigation for LCS, either to improve risk-stratification after nodule detection or to optimize risk-based patient selection for LDCT-based screening. Results from ongoing and future clinical trials will elucidate the clinical utility of biomarkers in the LCS paradigm.