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

项目总结/摘要 前列腺癌是一个巨大的公共卫生负担，在美国每年约有17万人被诊断出前列腺癌。的 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， 建议对约75，000例诊断的低风险前列腺癌进行积极监测 每年.主动监测方案各不相同，但都涉及监测，通常通过PSA检测和前列腺 活检，只有在有迹象表明可能发生更侵袭性的癌症时才建议进行治愈性治疗。 礼物然而，来自随机研究的新数据表明，在有限的监测下， 与那些接受直接化疗的人相比， 治愈性治疗目前迫切需要一种标记物来改善男性的风险分层， 主动监视的候选人更好的风险分层将改善积极监测的患者选择， 将确定适当和及时的触发治愈性治疗，并将优化和个性化 监测方案，例如监测前列腺活检的频率。 许多商业上可获得的分子生物标志物测定已经被开发用于前列腺癌 检测或用于高风险癌症的预后，并且其中几种正在作为测定法销售， 确定新诊断的前列腺癌的治疗与监测，但没有生物标志物， 在主动监测人群中进行了专门测试或验证。在这份提案中，我们将利用现有的 市售的检测试剂盒，其包含经分析验证的分子生物标志物，并对其进行评估 在主动监测中预测有临床意义的终点的新用途。我们将雇用一名 前瞻性-回顾性设计，询问来自大型多中心的注释良好的生物标本 金丝雀前列腺主动监测研究（PASS）队列。金丝雀PASS计划是一个多学科的 由临床研究者（泌尿科、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中，Canary PASS最适合验证检测， 他们可以在短期内融入临床实践。对于本提案中的工作， 与三个行业合作伙伴（GenomeDx、MDxHealth、OPKO Diagnostics）合作，以验证组织， 尿液和血液生物标记物用于主动监测。 在主动监测中成功实施检测以改善风险分层和预后 患者将减少过度治疗，改善监测方案，而不会增加癌症死亡率。

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.