Emerging Strategies in Lung Cancer Screening: Blood and Beyond

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.