Non Invasive Biomarkers for Diagnosing Clinically Significant Prostate Cancer

描述(申请人提供)：尽管许多新诊断的前列腺癌(PC)都有无痛的自然病史，但大多数男性仍然接受与副作用和成本相关的初级治疗，即过度治疗。显然有必要为本地化的个人电脑开发和实施新的管理策略，如果建立在对疾病状态和懒惰与攻击性行为的可能性的准确评估的基础上，这一策略将得到加强。这项提议将检验这样一种假设，即指示不良PC特征的生物标记物(例如高Gleason模式)可以在PC患者的尿液中重复检测到。我们进一步假设，对一组非侵入性尿液生物标记物的初始采样和随着时间的推移对这些标记物的重复评估将与前列腺癌中显著或轻微癌症的存在相关，因此可用于监测或继续进行明确治疗的决策。这些假说将通过特定的目标进行验证，这些目标旨在利用定量尿液分析和多机构纵向队列男性管理的不同的前列腺癌相关RNA，并伴随着生物标本、病理学和临床数据。这些目标的成功实现将为前列腺癌的初始和纵向评估提供非侵入性工具，以便为局部疾病的准确治疗决策提供信息。

DESCRIPTION (provided by applicant): Despite the indolent natural history of many newly diagnosed prostate cancers (PC), most men still undergo primary curative therapy with associated side effects and costs, i.e. overtreatment. There is an clear need for the development and implementation of new management strategies for localized PC which would be enhanced if founded upon accurate assessments of disease status and the potential for indolent versus aggressive behavior. This proposal will test the hypothesis that biomarkers indicative of adverse PC characteristics (e.g. high Gleason pattern) can be reproducibly detected in the urine of men with PC. We further hypothesize that initial sampling of a panel of noninvasive urine biomarkers and the repeated evaluation of these markers over time will associate with the presence of significant versus insignificant cancer in the prostate, and thus can be used in informing decisions for surveillance or proceeding with definitive treatment. These hypotheses will be tested through specific aims designed to exploit distinct prostate cancer-associated RNAs using quantitative urine assays and a multi-institutional longitudinal cohort of men managed by active surveillance with attendant biospecimens, pathological, and clinical data. The successful completion of these aims will provide non-invasive tools for the initial and longitudinal assessment of prostate cancers in order to inform accurate treatment decisions for localized disease.