Precision Medicine Approach to Prostate Cancer Active Surveillance

前列腺癌主动监测的精准医学方法

• 批准号: 8899479
• 负责人: DANIEL W. LIN
• 金额: $ 69.5万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8899479
• 关键词: Accounting; Active Sites; Adverse effects; Advisory Committees; Biological Assay; Biological Markers; Biopsy; Biopsy Specimen; Cancer Etiology; Cancer Patient; Cessation of life; Clinical; Clinical Management; Clinical Trials; Consensus; DNA; DNA Sequence; Data; Decision Making; Diagnosis; Disease; Disease Progression; Fluorescent in Situ Hybridization; Future; Genes; Genomics; Guidelines; Health; Indolent; Infection; International; Intervention; Kinetics; Lead; Left; Length; Longevity; Malignant Neoplasms; Malignant neoplasm of prostate; Modeling; Molecular; Monitor; Mutation; Newly Diagnosed; North America; Operative Surgical Procedures; PTEN gene; Pathway interactions; Patients; Population Control; Preventive; Prostate; Prostate-Specific Antigen; Protocols documentation; Publications; Radiation; Recommendation; Recording of previous events; Recurrence; Reverse Transcriptase Polymerase Chain Reaction; Risk; Risk Estimate; Screening for Prostate Cancer; Services; Slide; Staging; TMPRSS2 gene; Tissues; United States; Work; base; cohort; cost; disorder risk; follow-up; health related quality of life; men; migration; next generation; next generation sequencing; novel; outcome forecast; precision medicine; prospective; screening; standard of care; surveillance strategy; surveillance study; tumor progression; validation studies

DESCRIPTION (provided by applicant): Precision Medicine Approach to Prostate Cancer Active Surveillance Project Summary: Prostate cancer (PCa) accounts for over 28,000 deaths per year and was the second-greatest cause of cancer death among men in 2012. There will be over 241,000 new diagnoses of PCa this year with the majority opting for primary curative therapies, such as radiation or surgery, with associated potential side effects and subsequent declines in health related quality of life. Widespread use of prostate-specific antigen (PSA)-screening has led to profound stage migration, with the majority of newly diagnosed cases being clinically localized and of low grade. Such stage migration has resulted in the number of diagnoses far outnumbering the number of lethal cases, i.e. over diagnosis of those cancers that would never progress or cause harm to the patient if left untreated. Estimates of the proportion of over diagnosed PCa range from 15-84%, depending on the definition of occult or latent disease. PSA screening practices have changed minimally after publication of large PSA screening trials, and it is expected that even after the recent United States Preventive Services Task Force (USPSTF) recommendations, patients will continue to drive PCa screening, and other guidelines still promote informed decision-making. Given the often indolent course of screen-detected PCa, active surveillance (AS) - or careful monitoring of the cancer, most often with PSA kinetics and serial biopsy, with selected intervention based on these parameters - is an emerging initial management alternative for PCa that appears unlikely to threaten quality or length of life. AS is a management strategy for those with low-grade, low volume malignancy, who are followed carefully and treated with curative intent based on apparent progression. However, most AS strategies call for serial biopsies to determine whether there is disease progression, and these biopsies have potential complications such as infection. Supplementing AS with reliable biomarkers to predict disease progression would greatly enhance the appeal of this approach. We hypothesize that biomarkers of disease aggressiveness and prognosis can be interrogated in early stage PCa and that these biomarkers will reliably predict PCa progression and/or under-staging and grading. We aim to elucidate this challenge in this proposal. We will confirm a novel panel of tissue-based biomarkers to determine the presence of or progression to aggressive disease. This novel, biopsy-based multi-gene quantitative RT-PCR assay developed by Genomic Health, Oncotype DX Prostate Cancer Assay, discriminates aggressive from indolent cancer on multivariate modeling of prostate cancer patients. We will accomplish this using the PASS cohort (n=1000 men), the largest, prospective, multi- site AS study in North America. We will also evaluate emerging tissue-based biomarkers for aggressive PCa in men on AS using Next Generation DNA sequencing and will also assess on biopsy samples TMPRSS2:ERG and PTEN status and determine associations with aggressive PCa.

描述（由申请人提供）：前列腺癌主动监测项目的精确医学方法摘要：前列腺癌（PCA）每年占28,000多人死亡，是2012年男性癌症死亡的第二大原因。今年将有超过241,000个新的PCA诊断，而PCA将在今年的PCA诊断，大多数人选择主要的治疗疗法，例如，与远期治疗相关的效果相关的效果，并将其效果相关，并效果效果，并且效果效果以及效果以及效果的效果，并及其效果。前列腺特异性抗原（PSA）扫描的广泛使用导致了深刻的阶段迁移，大多数新诊断的病例都在临床上定位和低级。这种阶段的迁移导致诊断的数量远远超过了致命病例的数量，即，如果未经治疗，那些永远不会对患者造成伤害或损害的癌症的诊断。根据神秘或潜在疾病的定义，诊断过的PCA的比例估计值范围为15-84％。 PSA筛查实践在发布大型PSA筛查试验后的变化很小，并且预计即使在最近的美国预防服务工作组（USPSTF）建议之后，患者仍将继续进行PCA筛查，而其他准则仍然可以促进明智的决策。鉴于屏幕检测的PCA通常是顽固的过程，主动监视（AS）或仔细监测癌症（通常经常使用PSA动力学和连续活检），基于这些参数进行了精选干预 - 是PCA的一种新兴的初始管理替代方案，似乎不太可能威胁着质量或生命的长度。对于那些低度，低量恶性肿瘤的人的管理策略也是如此，他们经过了仔细的遵循并根据明显进展的治疗意图进行治疗。但是，大多数策略都要求进行连续活检以确定是否存在疾病进展，并且这些活检有潜在的并发症，例如感染。与可靠的生物标志物进行补充以预测疾病进展将大大增强这种方法的吸引力。我们假设可以在早期PCA中询问疾病侵略性和预后的生物标志物，并且这些生物标志物将可靠地预测PCA的进展和/或分期范围和分级。我们旨在在该提案中阐明这一挑战。我们将确认一个新型基于组织的生物标志物，以确定或进展为攻击性疾病。这款基于基因组健康开发的基于活检的新型多基因定量RT-PCR分析，Oncotype DX前列腺癌测定法，在前列腺癌患者的多元建模上歧视了侵略性的侵略性。我们将使用Pass队列（n = 1000名男子），最大的，前瞻性，多地点作为北美研究来实现这一目标。我们还将评估新兴组织的生物标志物在使用下一代DNA测序的男性中，以侵略性PCA，并将评估活检样品TMPRSS2：ERG和PTEN状态，并确定与攻击性PCA的关联。