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: 8673962
• 负责人: DANIEL W. LIN
• 金额: $ 74.72万
• 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/8673962
• 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; Future; Genes; Genomics; Guidelines; Health; Indolent; Infection; International; Intervention; Kinetics; Lead; Left; Length; Longevity; Malignant Neoplasms; Malignant neoplasm of prostate; Medicine; 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; 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）：前列腺癌主动监测的精准医学方法 项目摘要：前列腺癌 (PCa) 每年导致超过 28,000 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 例 PCa 新诊断，其中大多数选择主要治疗方法，例如放射或手术，其具有潜在的副作用以及随后的健康相关质量下降。生活。前列腺特异性抗原（PSA）筛查的广泛使用导致了深刻的分期迁移，大多数新诊断病例属于临床局限性且级别较低。这种阶段转移导致诊断数量远远超过致死病例数量，即对那些如果不治疗就永远不会进展或对患者造成伤害的癌症进行了过度诊断。根据隐匿性或潜伏性疾病的定义，过度诊断 PCa 的比例估计为 15-84%。在大型 PSA 筛查试验发表后，PSA 筛查实践发生了微小的变化，预计即使在最近的美国预防服务工作组 (USPSTF) 建议之后，患者仍将继续推动 PCa 筛查，而其他指南仍会促进知情决策。鉴于筛查检测到的 PCa 病程通常是惰性的，主动监测 (AS)——或者对癌症进行仔细监测，最常见的是 PSA 动力学和连续活检，并根据这些参数进行有选择的干预——是一种新兴的 PCa 初始管理替代方案，似乎不太可能威胁生命质量或寿命。 AS 是一种针对低级别、低体积恶性肿瘤患者的管理策略，对这些患者进行仔细随访，并根据明显进展进行治疗。然而，大多数AS策略要求进行连续活检以确定是否存在疾病进展，并且这些活检具有潜在的并发症，例如感染。用可靠的生物标志物补充 AS 来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 中询问疾病侵袭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 进展和/或分期不足和分级。我们的目标是在本提案中阐明这一挑战。我们将确认一组新的基于组织的生物标志物，以确定侵袭性疾病的存在或进展。这种由 Genomic Health 开发的新型基于活检的多基因定量 RT-PCR 检测 Oncotype DX 前列腺癌检测可在前列腺癌患者的多变量模型中区分侵袭性癌症和惰性癌症。我们将使用 PASS 队列（n=1000 名男性）来实现这一目标，这是北美最大的前瞻性多地点 AS 研究。我们还将使用下一代 DNA 测序评估男性 AS 侵袭性 PCa 的新兴组织生物标志物，还将评估活检样本 TMPRSS2:ERG 和 PTEN 状态，并确定与侵袭性 PCa 的关联。