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: 8495282
• 负责人: Javier Hernandez
• 金额: $ 41.36万
• 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/8495282
• 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; 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; screening; 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.

描述（由申请人提供）：前列腺癌是男性中最常见的非皮肤肿瘤，一生中约有六分之一的男性受其影响。目前控制该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，活检中未发现前列腺癌，而许多癌症低于“正常”水平。我们之前在18882人的前列腺癌预防试验（PCPT）中观察到，在接受非那雄胺（一种5 α还原酶2型抑制剂和一种用于改善排尿的药物）治疗的男性中，PSA是前列腺癌存在的更好预测因子。前列腺癌最重要的预测指标是开始使用非那雄胺后PSA的变化：PSA没有改变或增加的男性患前列腺癌的风险几乎是PSA下降65%或更多的男性的3倍。基于这些先前的观察，我们的假设是，在3个月的非那雄胺治疗期间，PSA速度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有效性，我们将招募500名前列腺癌风险中等（20-60%）且计划进行前列腺活检的男性，接受3个月的非那雄胺5mg /天的治疗。我们计划使用我们的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的比例随机分配给非那雄胺或安慰剂，每月进行PSA检测，3个月后进行前列腺活检。然后，我们将在这三个月的非那雄胺治疗期间评估PSA速度作为前列腺癌活检的生物标志物。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，并确定当加入PCPT前列腺癌风险计算器中使用的其他前列腺癌危险因素时，3个月非那雄胺PSA速度的独立诊断价值。我们还将PSA与非那雄胺联合治疗或代替PCPT风险计算器的表现与其他新开发的前列腺癌生物标志物（包括PCA3、[-2]ProPSA和TMPRSS2:ERG）进行比较，并评估这些额外的前列腺癌生物标志物对PCPT风险计算器表现的独立预测价值。该项目的长期目标是开发一种新的方法，以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，前列腺活检的成本相当高，而且存在感染和出血等潜在风险。