Fuessel Susanne, Wirth Manfred P
Department of Urology. University Hospital and Faculty of Medicine. Technische Universität Dresden. Dresden. Germany. National Center for Tumor Diseases (NCT), partner site Dresden. Dresden. Germany.
Arch Esp Urol. 2019 Mar;72(2):116-125.
Prostate cancer (PCa) is a very heterogeneous disease with unknown outcome at the time of first diagnosis. Multiple clinicopathological parameters andmodern imaging approaches are currently used to detect PCa and to assess the necessity of early or delayed treatment according to the predicted aggressiveness of the tumor. Despite regular adjustments of predictive systems based on histopathological factors such as the Gleason grading system or based on prostate MRI such as the Prostate Imaging Reporting and Data System (PIRADS) these tools for risk stratification of PCa patients still harbor significant limitations with regard to the accuracy of PCa outcome prediction. Therefore, great hopes have been placed on the use of biomolecular markers which might be more closely associated with the underlying biological characteristics of this tumor entity and able to predict the course of the disease better than clinical parameters. Such biomarkers are expected to serve as valuable tools not only to improve PCa diagnostics but also to enhance pre- and posttreatment risk stratification which could finally facilitate therapeutic decisions.In this review, current literature on genomic biomarkers used for PCa detection and early prediction of the tumor aggressiveness is examined. First, germline mutations and single nucleotide polymorphisms which might influence PCa onset are discussed in relation to the usefulness of targeted PCa screening approaches. Moreover, different urine- and tissue-based diagnostic tests assessing PCa-associated alterations on genetic, epigenetic and transcriptional level are reviewed. Most of these genomic biomarker assays were validated in large patient cohorts and their potential clinical usability could be proven. They provide useful diagnostic information to facilitate decisions with regard to screen men at risk to develop PCa or to repeat diagnostics in men with negative biopsy results, but persistent suspicion of cancer.Several assays can assist the early identification of patients with high-risk PCa, who potentially would need treatment, and may facilitate the selection of patients suitable for active surveillance. More evidence of the clinicalusability of such genomic PCa detection assays has to be provided by further prospective studies to support the transferability of these new diagnostic approaches to daily clinical practice.
前列腺癌(PCa)是一种非常异质性的疾病,在首次诊断时其预后未知。目前,多种临床病理参数和现代成像方法被用于检测PCa,并根据预测的肿瘤侵袭性评估早期或延迟治疗的必要性。尽管基于组织病理学因素(如Gleason分级系统)或基于前列腺MRI(如前列腺影像报告和数据系统(PIRADS))对预测系统进行了定期调整,但这些用于PCa患者风险分层的工具在PCa预后预测的准确性方面仍存在显著局限性。因此,人们对使用生物分子标志物寄予厚望,这些标志物可能与该肿瘤实体的潜在生物学特征更密切相关,并且比临床参数更能预测疾病进程。预计此类生物标志物不仅将成为改善PCa诊断的有价值工具,还能加强治疗前和治疗后的风险分层,最终有助于治疗决策。在本综述中,我们研究了用于PCa检测和肿瘤侵袭性早期预测的基因组生物标志物的当前文献。首先,讨论了可能影响PCa发病的种系突变和单核苷酸多态性与靶向PCa筛查方法的有用性之间的关系。此外,还综述了评估基因、表观遗传和转录水平上PCa相关改变的不同基于尿液和组织的诊断测试。这些基因组生物标志物检测中的大多数已在大型患者队列中得到验证,并且其潜在的临床可用性已得到证实。它们提供了有用的诊断信息,有助于就筛查有患PCa风险的男性或对活检结果为阴性但仍怀疑患有癌症的男性重复进行诊断做出决策。几种检测方法可以帮助早期识别可能需要治疗的高危PCa患者,并可能有助于选择适合进行主动监测的患者。此类基因组PCa检测方法的临床可用性还需要更多前瞻性研究提供证据,以支持这些新诊断方法向日常临床实践的可转移性。