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他们的疾病，他们可以通过接受积极的监测来选择推迟或避免手术或放射治疗。被诊断为低风险前列腺癌的患者是积极监测的理想对象。不幸的是，诊断时可用的临床和病理参数将低估或低估约三分之一的前列腺癌。因此，需要更好的策略来应对新诊断的、低风险的前列腺癌。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。为了解决在非高加索男性中明显缺乏良好的积极监测标准的问题，在不同的高加索人和非裔美国人队列中同时进行验证。该项目包括锡达斯-西奈医学中心、约翰霍普金斯大学、多伦多大学、罗斯威尔公园癌症研究所和GenomDx生物科学公司之间的学术-商业合作伙伴关系。该联盟将评估在大量前列腺切除术中训练和测试的信号，并确认这些信号可以预测前列腺癌的不良病理和疾病进展。现在很明显，过去接受过前列腺切除术的大多数患者都是积极监测的对象；因此，前列腺切除术的特征很可能与现代积极监测对象的诊断活检有关。具体目标是(1)验证前列腺针刺活检中的生物标记物，预测考虑积极监测的男性的不利病理和进展，以及(2)测试非裔美国人种族对生物标记物签名的影响。该联盟处于有利地位，可以快速翻译和推广有效签名，因为所有的分析都将在CLIA批准的实验室进行，研究调查人员在合作团体、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.