Department of Pathology, Detroit Medical Center University Laboratories, Wayne State University School of Medicine, Detroit, Michigan.
Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, Massachusetts.
JAMA Intern Med. 2023 Oct 1;183(10):1144-1151. doi: 10.1001/jamainternmed.2023.3603.
There has been great enthusiasm for the emerging technology of molecular-based tests to detect and quantify tumor DNA circulating in the bloodstream, colloquially known as a liquid biopsy. However, less attention has been given to how their clinical utility depends on the indication for testing, which includes a range of clinical situations, each presenting unique challenges.
Five indications for circulating tumor DNA (ctDNA) blood testing were considered. (1) For therapy selection, ctDNA tests can identify genetic alterations in patients with cancer amenable to targeted therapy, but most patients do not have a targetable alteration. (2) For response to therapy, the absence of residual tumor DNA following cancer surgery could reduce the use of adjuvant chemotherapy, but it is unclear that this will happen in practice. (3) For disease surveillance following cancer treatment, ctDNA tests may well detect cancer recurrence before symptoms appear, yet earlier intervention may have no effect on mortality. (4) For diagnosis of suspected cancer, ctDNA tests are able to identify some symptomatic cancers, but how they add to the conventional diagnostic evaluation is unknown. (5) For screening for cancer, multicancer tests can detect many types of cancer, but their low sensitivity for early-stage tumors raises questions as to whether screening can help patients live longer or live better.
Circulating tumor DNA tests are being promoted for multiple indications. Numerous studies are ongoing, but randomized clinical trials of their effect on patient-centered outcomes are rare. While these tests have the potential to improve care in selected indications, this must be proven, as they will add cost, complexity, and unintended adverse effects for patients.
新兴的基于分子的检测技术在检测和量化血液中循环的肿瘤 DNA 方面具有很大的优势，通俗地称为液体活检。然而，人们对其临床效用如何取决于检测的适应症关注较少，这些适应症包括一系列临床情况，每种情况都存在独特的挑战。
考虑了五种循环肿瘤 DNA (ctDNA) 血液检测的适应症。（1）对于治疗选择，ctDNA 测试可以识别对靶向治疗有反应的癌症患者的遗传改变，但大多数患者没有可靶向的改变。（2）对于治疗反应，癌症手术后残留肿瘤 DNA 的缺失可能会减少辅助化疗的使用，但实际上是否会发生这种情况尚不清楚。（3）用于癌症治疗后的疾病监测，ctDNA 测试很可能在症状出现之前检测到癌症复发，但早期干预可能对死亡率没有影响。（4）用于疑似癌症的诊断，ctDNA 测试能够识别一些有症状的癌症，但它们如何增加常规诊断评估尚不清楚。（5）用于癌症筛查，多癌种测试可以检测多种类型的癌症，但它们对早期肿瘤的低敏感性引发了关于筛查是否有助于患者活得更久或生活质量更高的问题。
循环肿瘤 DNA 测试正在被推广用于多种适应症。许多研究正在进行中，但关于它们对以患者为中心的结局影响的随机临床试验却很少。虽然这些测试有可能在选定的适应症中改善护理，但这必须得到证明，因为它们将增加成本、复杂性和对患者的意外不良影响。
