循环肿瘤 DNA（ctDNA，癌细胞脱落的 DNA）正在成为迄今为止发现的最具变革性的癌症生物标志物之一。尽管在癌症检测和患者管理的所有阶段都可能有用，但其最令人兴奋的可能性之一是作为相对无创的全癌症筛查测试。 Galleri 或 CancerSEEK 等 ctDNA 检测的初步结果表明，它们对恶性肿瘤具有很高的特异性 (> 99.0%)。它们的敏感性因癌症类型和疾病阶段而异，但在 I 期疾病患者中通常较低。与现有筛查策略相比，ctDNA 的一个主要优势是能够在一次测试中检测多种癌症类型。迄今为止发表的大多数研究的局限性在于，它们主要是病例对照研究，这些研究是在既往诊断为恶性肿瘤的患者中进行的，并使用表面健康的受试者作为对照。因此，如果这些测试用于无症状人群（即可能采用这些测试的人群）的筛查，则报告的敏感性、特异性和阳性预测值可能会较低。为了证明在无症状人群中的临床实用性，必须在大型随机前瞻性随机试验中证明这些测试可以降低癌症死亡率，而不会导致过度诊断。 Galleri 和 CancerSEEK 目前正在进行此类试验。

Circulating tumor DNA (ctDNA, DNA shed by cancer cells) is emerging as one of the most transformative cancer biomarkers discovered to-date. Although potentially useful at all the phases of cancer detection and patient management, one of its most exciting possibilities is as a relatively noninvasive pan-cancer screening test. Preliminary findings with ctDNA tests such as Galleri or CancerSEEK suggest that they have high specificity (> 99.0%) for malignancy. Their sensitivity varies depending on the type of cancer and stage of disease but it is generally low in patients with stage I disease. A major advantage of ctDNA over existing screening strategies is the potential ability to detect multiple cancer types in a single test. A limitation of most studies published to-date is that they are predominantly case-control investigations that were carried out in patients with a previous diagnosis of malignancy and that used apparently healthy subjects as controls. Consequently, the reported sensitivities, specificities and positive predictive values might be lower if the tests are used for screening in asymptomatic populations, that is, in the population where these tests are likely be employed. To demonstrate clinical utility in an asymptomatic population, these tests must be shown to reduce cancer mortality without causing excessive overdiagnosis in a large randomized prospective randomized trial. Such trials are currently ongoing for Galleri and CancerSEEK.