The role of biomarkers is crucial in oncology for both early diagnosis and the personalization of cancer treatments. Tissue biomarkers have gained a central role as predictors of the response to an increasing number of anticancer agents; conversely, the clinical role of circulating biomarkers (c-TMs) is limited and has remained almost unchanged over the years. The position of guidelines is summarized and discussed with reference to the potential usefulness of c-TMs in those areas of application that cannot be covered by tissue biomarkers. The pipeline of translational research on biomarkers is briefly described; the differences among analytical validation, clinical validation, and clinical utility are discussed, emphasizing that the assessment of clinical utility is the ultimate step toward clinical use. The role of monitoring of appropriateness as a proxy indicator of how the research pipeline has actually worked is discussed, and data and c-TMs overordering rates are reported. The role and limits of guidelines to influence appropriate c-TMs ordering are discussed. The design of primary studies on c-TMs is examined, underlining that they mainly focus on clinical validation rather than on clinical utility. The role of regulatory boards is also briefly presented and discussed.

中文翻译：

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循环癌症生物标志物的技术水平和趋势。

对于肿瘤的早期诊断和个性化治疗，生物标志物的作用在肿瘤学中至关重要。组织生物标志物已成为预测对越来越多的抗癌药反应的核心作用。相反，循环生物标志物（c-TMs）的临床作用是有限的，多年来一直保持不变。总结了指南的位置，并参考了c-TM在组织生物标志物无法覆盖的应用领域中的潜在用途。简要介绍了生物标记物的翻译研究流程；讨论了分析验证，临床验证和临床效用之间的差异，强调了对临床效用的评估是迈向临床使用的最终步骤。讨论了适当性监测作为研究管道实际工作方式的代理指标的作用，并报告了数据和c-TMs的超额订购率。讨论了影响适当c-TM排序的准则的作用和局限性。对c-TMs的基础研究设计进行了检查，强调它们主要侧重于临床验证而不是临床实用性。还简要介绍和讨论了监管委员会的作用。