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

评估商用前列腺癌检测方法以加速主动监测中的新应用

• 批准号: 10217046
• 负责人: DANIEL W. LIN
• 金额: $ 19.45万
• 依托单位: FRED HUTCHINSON CANCER RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-18 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10217046
• 关键词: Address; American; Biological; Biological Assay; Biological Markers; Biopsy; Caring; Cessation of life; Clinical; Clinical Data; Clinical Investigator; Clinical Management; Clinical stratification; Cohort Studies; Collaborations; Costs and Benefits; Data; Diagnosis; Diagnostic; Disease; Disseminated Malignant Neoplasm; Evaluation; Genomics; Gleason Grade for Prostate Cancer; Goals; Health; High-Risk Cancer; Indolent; Infrastructure; Intervention; Laboratory Scientists; Malignant Neoplasms; Malignant neoplasm of prostate; Manufacturer Name; Marketing; Measurement; Medical Oncology; Modeling; Monitor; Neoplasm Metastasis; Newly Diagnosed; Operative Surgical Procedures; Outpatients; PSA screening; Pathology; Patient Selection; Patients; Performance; Population; Population Surveillance; Prognosis; Prostate; Prostate Cancer therapy; Protocols documentation; Public Health; Quality of life; Radical Prostatectomy; Randomized; Recommendation; Recurrence; Regimen; Research Design; Retrospective Studies; Risk; Schedule; Screening for Prostate Cancer; Serinus; Testing; Therapeutic Intervention; Time; Tissues; Uncertainty; Urine; Urology; Validation; Work; base; biomarker panel; biomarker validation; blood-based biomarker; cancer care; cancer diagnosis; cancer risk; clinical application; clinical practice; clinical predictors; clinical risk; cohort; combinatorial; cost; curative treatments; design; disorder risk; experience; genomic signature; high risk; improved; industry partner; men; molecular marker; multidisciplinary; novel; novel marker; overtreatment; patient stratification; programs; prospective; prostate biopsy; prostate cancer risk; risk prediction; risk stratification; side effect; surveillance study; tumor

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.

项目摘要/摘要 前列腺癌是一个巨大的公共卫生负担，每年在美国诊断出约170,000名男性。这 大多数被诊断为前列腺癌的男性即使没有治疗，也不会死于癌症，导致 大约75,000个低风险前列腺癌的主动监视的建议 每年。主动监视协议各不相同，但所有这些都涉及监测，通常是通过PSA测试和前列腺 活检，仅当有迹象表明可能是更多侵略性癌症的情况下，才建议进行治疗治疗 展示。但是，来自随机研究的新兴数据表明，监测有限的数据明显更多 与接受立即发生的患者相比 治疗治疗。迫切需要标记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患者选择主动监视， 将确定适当及时的治疗治疗触发因素，并将优化和个性化 监视方案，例如进行监视前列腺活检的频率。 已经开发了许多用于前列腺癌的市售分子生物标志物测定 检测或预后较高的风险癌症，其中一些被销售为 确定对新诊断的前列腺癌的治疗与监视，但没有生物标志物是 在主动监视人群中进行了测试或验证。在此提案中，我们将利用现有 纳入分析验证的分子生物标志物并对其进行评估的市售测定法 用于预测主动监视中临床意义有意义的终点的新颖使用。我们将采用一个 前瞻性回归设计，从大型多中心询问宣布良好的生物测量 金丝雀前列腺主动监视研究（PASS）队列。金丝雀通行计划是一个多学科 临床研究人员（泌尿外科，医学肿瘤学，病理学），统计学家和临床实验室的小组 科学家。与商业合作伙伴合作，Canary Pass可以最佳地验证测定法 可以在短期内将它们纳入临床实践。对于此提案中的工作，我们将利用 与三个行业合作伙伴（Genomedx，MDXHealth，OPKO诊断）的合作，以验证组织， 尿液和基于血液的生物标志物用于主动监测。 成功实施测定方法，以改善主动监视的风险分层和预后 患者将减少过度治疗并改善监测方案而不会增加癌症死亡。