Non Invasive Biomarkers for Diagnosing Clinically Significant Prostate Cancer

描述（由申请人提供）：尽管许多新诊断的前列腺癌（PC）有不痛的自然病史，但大多数男性仍然接受初级治疗，伴有相关的副作用和费用，即过度治疗。显然，有必要开发和实施针对局部PC的新管理策略，如果基于对疾病状态的准确评估以及惰性与侵袭性行为的可能性，这些策略将得到加强。该提案将验证这样一种假设，即表明不良PC特征的生物标志物（如高格里森模式）可以在PC患者的尿液中可重复检测到。我们进一步假设，一组非侵入性尿液生物标志物的初始采样和随着时间的推移对这些标志物的重复评估将与前列腺中存在的显著或不显著的癌症有关，因此可以用于为监测决策提供信息或进行最终治疗。这些假设将通过特定的目标来验证，这些目标旨在利用定量尿液分析和多机构纵向男性队列，通过积极监测伴随的生物标本、病理和临床数据来利用不同的前列腺癌相关rna。这些目标的成功完成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.