Qualifying Multi-Transcript Signatures for Active Surveillance of Prostate Cancer

描述（由申请人提供）：绝大多数被诊断患有前列腺癌的男性不会死于疾病，并且可以通过积极监测来选择延迟或避免手术或放射治疗。被诊断患有前列腺癌且被归类为低风险的患者是主动监测的理想候选人。不幸的是，在诊断时可用的临床和病理参数将在大约1/3的所有病例中对前列腺癌进行分期或降级。因此，需要更好的策略来对新诊断的低风险前列腺癌进行风险策略。拟议项目的目标是评估现有的基于RNA的多分析物特征，用于前列腺癌诊断时的风险分层。为了解决明显缺乏在非白种人男性中进行主动监测的既定标准的问题，在单独的白种人和非洲裔美国人队列中平行进行验证。该项目由Cedars-Sinai医学中心、约翰霍普金斯、多伦多大学、罗斯韦尔公园癌症研究所和GenomDx Biosciences之间的学术-商业合作伙伴关系组成。该联盟将评估在大量前列腺切除术中训练和测试的签名，并确认其可预测不良前列腺癌病理学和疾病进展。现在很清楚，过去接受过膀胱切除术的大多数患者都是主动监测的候选人;因此，膀胱切除术的签名可能与现代主动监测候选人的诊断性活检相关。具体目的是（1）验证前列腺穿刺活检中的生物标志物预测考虑主动监测的男性的不良病理和进展，以及（2）测试非裔美国人种族对生物标志物特征的影响。该联盟有能力快速翻译和推广经验证的签名，因为所有检测都将在CLIA批准的实验室中进行，研究者在合作小组、国家专业协会和国家指南委员会中担任领导职务。

DESCRIPTION (provided by applicant): The vast majority of men diagnosed with prostate cancer do not die of their disease and can choose to delay or avoid surgical or radiation treatment by undergoing active surveillance. Patients diagnosed with prostate cancer that is categorized as low risk are ideal candidates for active surveillance. Unfortunately, clinical and pathologic parameters available at the time of diagnosis will understage or undergrade prostate cancer in approximately 1/3 of all cases. Therefore, better strategies are needed to risk-stratefy newly diagnosed, low risk prostate cancer. The goal of the proposed project is to evaluate existing RNA-based multi-analyte signatures for risk-stratification at the time of prostate cancer diagnosis. To address the glaring absence of well-established criteria for active surveillance in non-Caucasian men, the validation is performed in parallel in separate Caucasian and African-American cohorts. The project consists of an academic-commercial partnership between Cedars-Sinai Medical Center, Johns Hopkins, University of Toronto, Roswell Park Cancer Institute, and GenomDx Biosciences. The consortium will evaluate signatures trained and tested in large numbers of prostatectomies and confirmed to be predictive of adverse prostate cancer pathology and disease progression. It is now clear that majority of patients who have undergone prostatectomy in the past are candidates for active surveillance; therefore, signatures from prostatectomies are likely to be relevant to diagnostic biopsies from modern active surveillance candidates. The specific aims are (1) to validate biomarkers in prostate needle biopsies predictive of adverse pathology and progression in men considering active surveillance and (2) to test the effects of African-American ethnicity on the biomarker signatures. The consortium is well-positioned to rapidly translate and promote validated signatures since all assays will be performed in a CLIA-approved laboratories, and study investigators have leadership positions in cooperative groups, national professional societies, and national guidelines committees.