Background: Second-generation androgen receptor signaling inhibitors are one of the main treatment options in metastatic castration-resistant prostate cancer (mCRPC). Nonetheless, a considerable proportion show limited response to treatment, which indicates the need for convenient, easily accessible predictor biomarkers, a role suited for liquid biopsy.Methods: We conducted a PRISMA-compliant systematic review of four databases (Embase, Medline, Scopus, Web of Science) to identify all studies (observational studies and clinical trials) investigating cell-free DNA, circulating tumor cells, exosomes, and circulating RNAs as prognostic markers in metastatic castration-resistant patients starting androgen receptor signaling inhibitors. We excluded studies that evaluated combination therapies, rare histological subtypes or included nonmetastatic or castrate-sensitive disease. We also evaluated whether published papers followed reporting guidelines (REMARK, STROBE, or CONSORT for abstracts).Results: We identified a total of 123 reports, from which we identified only a few well-studied and consistent biomarkers: androgen receptor overexpression/copy number gain and splice variant 7, as well as disease burden markers (circulating tumor DNA fraction and circulating tumor cell concentration). Alterations or copy number loss in tumor suppressors PTEN, RB1, and TP53 were second in terms of quantity and consistency of evidence. However, a large majority of identified biomarkers were relatively understudied or inconsistent. We identified two potential vulnerabilities: inconsistent adherence to reporting guidelines and the under-inclusion of patients of non-Western European ancestry.Conclusions: A large number of biomarkers were linked to worse outcomes in prostate cancer; nonetheless, in most cases, the evidence is limited or inconsistent, or even contradictory. The main exceptions pertain to androgen receptor signaling and disease burden, and, to a smaller extent, to certain tumor suppressor genes. Further studies are needed to confirm their clinical utility, using clear and consistent methodologies and including patients from currently understudied populations.
背景：第二代雄激素受体信号抑制剂是转移性去势抵抗性前列腺癌（mCRPC）的主要治疗选择之一。然而，相当一部分患者对治疗反应有限，这表明需要便捷、易获取的预测性生物标志物，而液体活检正适合这一角色。 方法：我们按照PRISMA指南对四个数据库（Embase、Medline、Scopus、Web of Science）进行了系统综述，以确定所有研究（观察性研究和临床试验），这些研究调查了在开始使用雄激素受体信号抑制剂的转移性去势抵抗性患者中，游离DNA、循环肿瘤细胞、外泌体和循环RNA作为预后标志物的作用。我们排除了评估联合疗法、罕见组织学亚型或包含非转移性或去势敏感性疾病的研究。我们还评估了已发表的论文是否遵循报告指南（REMARK、STROBE或CONSORT摘要指南）。 结果：我们共确定了123篇报告，从中仅发现少数经过充分研究且一致的生物标志物：雄激素受体过表达/拷贝数增加和剪接变体7，以及疾病负担标志物（循环肿瘤DNA分数和循环肿瘤细胞浓度）。肿瘤抑制基因PTEN、RB1和TP53的突变或拷贝数丢失在证据的数量和一致性方面位居第二。然而，绝大多数已确定的生物标志物研究相对不足或结果不一致。我们发现了两个潜在的缺陷：对报告指南的遵循不一致，以及对非西欧血统患者的纳入不足。 结论：大量生物标志物与前列腺癌的不良预后相关；然而，在大多数情况下，证据有限或不一致，甚至相互矛盾。主要的例外涉及雄激素受体信号和疾病负担，以及在较小程度上涉及某些肿瘤抑制基因。需要进一步研究以确认其临床实用性，使用清晰一致的方法，并纳入目前研究不足的人群中的患者。
肿瘤(癌症)患者之家