Background: Prostate cancer (PCa) is one of the most frequently occurring malignancies. Although most cases are not life-threatening, approximately 20% endure an unfavorable outcome. PSA-based screening reduced mortality but at the cost of an increased overdiagnosis/overtreatment of low-risk (lrPCa) and favorable intermediate-risk (firPCa) PCa. PCa risk-groups are usually identified based on serum Prostate-Specific Antigen (PSA), the Gleason score, and clinical T stage, which have consistent although variable specificity or subjectivity. Thus, more effective and specific tools for risk assessment are needed, ideally making use of minimally invasive methods such as liquid biopsies. In this systematic review we assessed the clinical potential and analytical performance of liquid biopsy-based biomarkers for pre-treatment risk stratification of PCa patients. Methods: Studies that assessed PCa pre-treatment risk were retrieved from PubMed, Scopus, and MedLine. PCa risk biomarkers were analyzed, and the studies’ quality was assessed using the QUADAS-2 tool. Results: The final analysis comprised 24 full-text articles, in which case-control studies predominated, mostly reporting urine-based biomarkers (54.2%) and biomarker quantification by qPCR (41.7%). Categorization into risk groups was heterogeneous, predominantly making use of the Gleason score. Conclusion: This systematic review unveils the substantial clinical promise of using circulating biomarkers in assessing the risk for prostate cancer patients. However, the standardization of groups, categories, and biomarker validation are mandatory before this technique can be implemented. Circulating biomarkers might represent a viable alternative to currently available tools, obviating the need for tissue biopsies, and allowing for faster and more cost-effective testing, with superior analytical performance, specificity, and reproducibility.
背景：前列腺癌（PCa）是最常见的恶性肿瘤之一。尽管大多数病例不危及生命，但约20%的患者预后不良。基于前列腺特异性抗原（PSA）的筛查降低了死亡率，但代价是增加了对低风险（lrPCa）和有利中风险（firPCa）前列腺癌的过度诊断/过度治疗。前列腺癌风险分组通常基于血清前列腺特异性抗原（PSA）、格里森评分和临床T分期进行划分，这些指标虽具有一致性，但其特异性或主观性存在差异。因此，需要更有效、更特异的风险评估工具，理想情况下应利用液体活检等微创方法。本系统综述评估了基于液体活检的生物标志物在前列腺癌患者治疗前风险分层中的临床潜力与分析性能。 方法：从PubMed、Scopus和MedLine数据库中检索评估前列腺癌治疗前风险的研究。对前列腺癌风险生物标志物进行分析，并使用QUADAS-2工具评估研究质量。 结果：最终分析纳入24篇全文文献，其中病例对照研究占主导地位，主要报告尿液生物标志物（54.2%）和通过qPCR进行生物标志物定量分析（41.7%）。风险分组标准存在异质性，主要采用格里森评分进行划分。 结论：本系统综述揭示了循环生物标志物在评估前列腺癌患者风险方面具有显著的临床前景。然而，在实施该技术前，必须对分组标准、分类方法和生物标志物验证进行标准化。循环生物标志物可能成为现有工具的有效替代方案，避免组织活检的需要，实现更快速、更具成本效益的检测，并具有更优的分析性能、特异性和可重复性。
Biomarkers for Pre-Treatment Risk Stratification of Prostate Cancer Patients: A Systematic Review
肿瘤(癌症)患者之家