Circulating tumor DNA (ctDNA) enables real-time genomic profiling of cancer without the need for tissue biopsy. ctDNA-based technology is seeing rapid uptake in clinical practice due to the potential to inform patient management from diagnosis to advanced disease. In metastatic disease, ctDNA can identify somatic mutations, copy-number variants (CNVs), and structural rearrangements that are predictive of therapy response. However, the ctDNA fraction (ctDNA%) is unpredictable and confounds variant detection strategies, undermining confidence in liquid biopsy results. Assay design also influences which types of genomic alterations are identifiable. Here, we describe the relationships between ctDNA%, methodology, and sensitivity–specificity for major classes of genomic alterations in prostate cancer. We provide recommendations to navigate the technical complexities that constrain the detection of clinically relevant genomic alterations in ctDNA.

循环肿瘤 DNA (ctDNA) 可以在不需要组织活检的情况下对癌症进行实时基因组分析。由于有可能为从诊断到晚期疾病的患者管理提供信息，因此基于 ctDNA 的技术正在临床实践中迅速普及。在转移性疾病中，ctDNA 可以识别预测治疗反应的体细胞突变、拷贝数变异 (CNV) 和结构重排。然而，ctDNA 分数 (ctDNA%) 是不可预测的，并且会混淆变异检测策略，从而削弱对液体活检结果的信心。分析设计也会影响可识别的基因组改变类型。在这里，我们描述了前列腺癌中主要基因组改变类别的 ctDNA%、方法和敏感性-特异性之间的关系。