Improving prostate biopsy efficiency: The finasteride challenge test

提高前列腺活检效率：非那雄胺激发试验

• 批准号: 8137196
• 负责人: IAN M. THOMPSON
• 金额: $ 44.32万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-02 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137196
• 关键词: Affect; Area; Biological Markers; Biopsy; Blood Tests; Cancer Detection; Characteristics; Clinical; Collection; Controlled Clinical Trials; Detection; Diagnosis; Diagnostic; Digital Rectal Examination; Disease Marker; Drug usage; Early Diagnosis; Early treatment; Eligibility Determination; Enzymes; Epithelium; Finasteride; Gene Fusion; Goals; Hemorrhage; Hyperplasia; Infection; Malignant Neoplasms; Malignant neoplasm of prostate; Methodology; Methods; National Cancer Institute; Neoplasms; Oxidoreductase; Performance; Persons; Pharmaceutical Preparations; Placebo Control; Placebos; Predictive Value; Procedures; Production; Prostate; Prostate Cancer Prevention Trial; Prostate-Specific Antigen; Public Health; Randomized; Receiver Operating Characteristics; Recommendation; Recruitment Activity; Risk; Risk Factors; Schedule; Screening for Prostate Cancer; Screening procedure; Serum; TMPRSS2 gene; Testing; United States; Urination; base; cancer risk; cost; disorder control; falls; improved; inhibitor/antagonist; man; men; novel; older men; performance tests; prospective; prostate enlargement; public health relevance; statistics

DESCRIPTION (provided by applicant): Prostate cancer is the most common non-dermatologic neoplasm in men, affecting about one man in six in his lifetime. The primary public health approach for control of this disease is currently early diagnosis and treatment, relying primarily on the Prostate Specific Antigen (PSA) blood test for detection. Unfortunately, for most men with a PSA above 4.0 ng/mL (the most commonly-applied upper limit of normal), no prostate cancer is found at biopsy while many cancers are found below this 'normal' level. We have previously observed in the 18,882-person Prostate Cancer Prevention Trial (PCPT), a National Cancer Institute-sponsored study, that in men who received the drug finasteride, an inhibitor of the five alpha reductase type 2 enzyme and a medication used to improve urination, PSA was a better predictor of presence of prostate cancer. The most important predictor of the presence of prostate cancer was the change in PSA after beginning finasteride: men whose PSA did not change or increased had an almost 3-fold greater risk of having prostate cancer than those whose PSA decreased by 65% or more. Our hypothesis, based on these previous observations, is that PSA velocity during a 3-month treatment with finasteride more accurately predicts presence or absence of prostate cancer. To demonstrate the clinical usefulness of this test, we will recruit 500 men with an intermediate (20-60%) risk of prostate cancer and who are planning to undergo prostate biopsy to receive 3 months of finasteride at 5 mg/day. We plan to use our PCPT prostate cancer risk calculator to determine prostate cancer risk and subject eligibility. These men will be randomized in a 4:1 fashion to finasteride or placebo, will have PSA testing monthly and after 3 months will undergo prostate biopsy. We will then evaluate PSA velocity during these three months of finasteride treatment as a biomarker of prostate cancer on biopsy. We will then characterize the operating characteristics of PSA and digital rectal examination before and after finasteride treatment as well as determine the independent diagnostic value of the 3-month finasteride PSA velocity when added to the other prostate cancer risk factors used in the PCPT prostate cancer risk calculator. We will also compare the performance of PSA with finasteride treatment in combination or in place of the PCPT Risk Calculator to other newly developed prostate cancer biomarkers including PCA3, [-2]ProPSA, and TMPRSS2:ERG and evaluate the independent predictive value of these additional prostate cancer biomarkers on the performance of the PCPT Risk Calculator. The long term goal of this project is to develop a new methodology to improve prostate cancer detection while reducing the number of unnecessary prostate biopsies, procedures that are associated with considerable cost as well as potential for risks including infection and bleeding. PUBLIC HEALTH RELEVANCE: Hundreds of thousands of negative prostate biopsies occur each year in the US, most commonly prompted by an elevated PSA test. Finasteride, a drug used to treat prostate enlargement, appears to make PSA a more reliable test for cancer. We will determine if 3 months of treatment with finasteride will improve prostate cancer detection, with the potential for eliminating many of these unnecessary prostate biopsies.

描述（由申请人提供）：前列腺癌是男性最常见的非皮肤肿瘤，约六分之一的男性一生受其影响。目前控制这种疾病的主要公共卫生方法是早期诊断和治疗，主要依靠前列腺特异性抗原（PSA）血液检测进行检测。不幸的是，对于大多数 PSA 高于 4.0 ng/mL（最常用的正常上限）的男性来说，活检时没有发现前列腺癌，而许多癌症却低于这个“正常”水平。我们之前在美国国家癌症研究所赞助的一项 18,882 人前列腺癌预防试验 (PCPT) 中观察到，在接受药物非那雄胺（一种 5 α 还原酶 2 型酶抑制剂）和一种用于改善前列腺癌症状的药物的男性中，排尿、PSA 是前列腺癌存在的更好预测指标。前列腺癌最重要的预测因素是开始使用非那雄胺后 PSA 的变化：PSA 没有变化或增加的男性患前列腺癌的风险比 PSA 下降 65% 或更多的男性高出近 3 倍。基于这些先前的观察，我们的假设是非那雄胺治疗 3 个月期间 PSA 速度可以更准确地预测前列腺癌的存在或不存在。为了证明该测试的临床实用性，我们将招募 500 名具有中等 (20-60%) 前列腺癌风险并计划进行前列腺活检的男性，接受 3 个月的非那雄胺 5 毫克/天的治疗。我们计划使用 PCPT 前列腺癌风险计算器来确定前列腺癌风险和受试者资格。这些男性将以 4:1 的方式随机分配服用非那雄胺或安慰剂，每月进行 PSA 检测，3 个月后将接受前列腺活检。然后，我们将评估这三个月非那雄胺治疗期间的 PSA 速度，作为活检时前列腺癌的生物标志物。然后，我们将描述非那雄胺治疗前后 PSA 和直肠指检的操作特征，并确定 3 个月非那雄胺 PSA 速度与 PCPT 前列腺癌风险中使用的其他前列腺癌风险因素相结合时的独立诊断价值计算器。我们还将比较 PSA 与非那雄胺治疗联合或代替 PCPT 风险计算器与其他新开发的前列腺癌生物标志物（包括 PCA3、[-2]ProPSA 和 TMPRSS2:ERG）的性能，并评估这些附加的独立预测价值前列腺癌生物标志物对 PCPT 风险计算器性能的影响。该项目的长期目标是开发一种新的方法来改善前列腺癌的检测，同时减少不必要的前列腺活检的数量，这些手术涉及相当大的成本以及潜在的风险，包括感染和出血。 公共健康相关性：美国每年都会发生数十万例前列腺活检呈阴性，最常见的原因是 PSA 测试升高。非那雄胺是一种用于治疗前列腺肥大的药物，似乎使 PSA 成为更可靠的癌症检测方法。我们将确定 3 个月的非那雄胺治疗是否会改善前列腺癌的检测，并有可能消除许多不必要的前列腺活检。