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.

中文翻译：

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肺癌筛查的新兴策略：血液及其他筛查

背景虽然基于低剂量计算机断层扫描 (LDCT) 的肺癌筛查 (LCS) 可以降低高危人群中与肺癌相​​关的死亡率，但它仍然是一个不完善且基本上未得到充分利用的过程。基于 LDCT 的 LCS 可能会导致假阳性结果，从而导致侵入性操作和潜在的发病率。相反，当前的指导方针可能无法捕捉到高危人群，特别是那些来自代表性不足的少数群体的人群。为了解决这些局限性，出现了许多生物标志物来补充 LDCT 并改善早期肺癌检测。内容 本综述主要关注当前 LCS 临床开发中的基于血液的生物标志物，包括蛋白质、microRNA、循环 DNA 和甲基化 DNA 组合。我们还检查了其他正在研究中的新兴生物标志物——利用气道上皮、呼出气、痰和尿液。我们重点介绍生物标志物测试的挑战和局限性，以及将分子策略与成像技术相结合的最新策略。摘要 LCS 的多种生物标志物正在积极研究中，以改善结节检测后的风险分层，或优化基于风险的患者选择以进行基于 LDCT 的筛查。正在进行和未来的临床试验的结果将阐明 LCS 范式中生物标志物的临床效用。