Evaluation of commercially available prostate cancer assays to accelerate novel applications in active surveillance

项目摘要/摘要 前列腺癌是一个巨大的公共健康负担，美国每年约有17万名男性被诊断患有前列腺癌。这个 大多数被诊断患有前列腺癌的男性即使不接受治疗也不会死于癌症，导致 建议对确诊的约75,000例低危前列腺癌进行主动监测 每年。主动监测方案各不相同，但都涉及监测，通常是通过PSA检测和前列腺 活组织检查，只有在有迹象表明更具侵袭性的癌症可能是 现在时。然而，来自随机研究的新数据表明，在有限的监测下，更多的 与那些立即接受治疗的人相比，男性有临床进展或发展为转移癌 根治疗法。迫切需要标记物来改善男性患者的风险分层 积极监视的候选人。更好的风险分层将改善主动监测的患者选择， 将确定适当和及时的治疗触发因素，并将优化和个性化 监测方案，例如多久进行一次监测前列腺活检。 许多商业化的前列腺癌分子生物标志物检测方法已经被开发出来。 对高危癌症的检测或预后，其中几种方法正在市场上作为 确定新诊断的前列腺癌的治疗和监测，但还没有生物标记物 在现役监测人群中进行了专门测试或验证。在这个提案中，我们将利用现有的 商业上可用的包含分析验证的分子生物标记物并对其进行评估的检测方法 在主动监测中预测具有临床意义的终点的新用途。我们将聘请一名 从大型多中心询问注解良好的生物标本的前瞻性-回顾性设计 金丝雀前列腺主动监测研究(PASS)队列。金丝雀通行证计划是一个多学科的项目 由临床研究人员(泌尿外科、内科肿瘤学、病理学)、统计学家和临床实验室组成的小组 科学家。在与商业合作伙伴的合作下，Canary Pass最适合验证检测结果 他们可以在短期内整合到临床实践中。对于本提案中的工作，我们将利用 与三个行业合作伙伴(GenomeDx、MDxHealth、OPKO诊断)合作验证组织， 用于主动监测的尿液和血液生物标记物。 在主动监测中成功实施了改善风险分层和预后的分析方法 患者将减少过度治疗，并在不增加癌症死亡的情况下改进监测方案。

PROJECT SUMMARY/ABSTRACT Prostate cancer is a large public health burden, with about 170,000 men diagnosed annually in the US. The majority of men diagnosed with prostate cancer will not die from their cancer even if it is not treated, leading to the recommendation of active surveillance for the approximately 75,000 low risk prostate cancers diagnosed each year. Active surveillance protocols vary, but all involve monitoring, usually by PSA testing and prostate biopsy, with curative treatment recommended only if there are indications that more aggressive cancer may be present. Yet, emerging data from randomized studies suggest that with limited monitoring significantly more men have clinical progression or develop metastatic cancer when compared to those who undergo immediate curative treatment. There is an urgent need for markers that improve risk stratification for men who are candidates for active surveillance. Better risk stratification will improve patient selection for active surveillance, will identify appropriate and timely triggers for curative treatment, and will optimize and personalize surveillance regimens, e.g. how often to perform surveillance prostate biopsy. Many commercially available molecular biomarker assays have been developed for prostate cancer detection or for prognosis of higher risk cancers, and several of these are being marketed as assays that determine treatment versus surveillance for newly diagnosed prostate cancer, but no biomarkers have been tested or validated specifically in the active surveillance population. In this proposal, we will utilize existing commercially available assays that incorporate analytically validated molecular biomarkers and evaluate them for a novel use of predicting clinically meaningful endpoints in active surveillance. We will employ a prospective-retrospective design to interrogate well-annotated biospecimens from the large multi-center Canary Prostate Active Surveillance Study (PASS) cohort. The Canary PASS program is a multi-disciplinary group with clinical investigators (urology, medical oncology, pathology), statisticians, and clinical laboratory scientists. In collaboration with commercial partners, Canary PASS is optimally poised to validate assays so that they can be integrated into clinical practice in the near term. For the work in this proposal we will leverage collaborations with three industry partners (GenomeDx, MDxHealth, OPKO Diagnostics) to validate tissue, urine, and blood-based biomarkers for use in active surveillance. Successful implementation of assays for improved risk stratification and prognosis in active surveillance patients will reduce overtreatment and improve surveillance regimens without increasing cancer deaths.