Improving prostate biopsy efficiency: The finasteride challenge test

描述(申请人提供)：前列腺癌是男性中最常见的非皮肤病肿瘤，一生中约有六分之一的人会受到影响。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。不幸的是，对于PSA高于4.0 ng/ml(最常用的正常上限)的大多数男性来说，活组织检查没有发现前列腺癌，而许多癌症被发现低于这一正常水平。我们之前在18882人的前列腺癌预防试验(PCPT)中观察到，这是一项由国家癌症研究所赞助的研究，在接受药物非那雄胺、五α还原酶2型酶抑制剂和用于改善排尿的药物的男性中，PSA更好地预测前列腺癌的存在。前列腺癌最重要的预测指标是服用非那雄胺后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，在非那雄胺治疗的3个月期间，PSA速度更准确地预测前列腺癌的存在或不存在。为了证明这项测试的临床有效性，我们将招募500名前列腺癌风险中等(20%-60%)的男性，他们计划接受前列腺活检，接受3个月的非那雄胺治疗，每天5毫克。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的方式随机服用非那雄胺或安慰剂，每月进行PSA检测，3个月后接受前列腺活检。然后，我们将在非那雄胺治疗的这三个月中评估PSA速度，作为前列腺癌的生物标志物进行活检。然后，我们将描述非那雄胺治疗前后PSA的操作特点和直肠指诊，并确定3个月非那雄胺PSA速度与PCPT前列腺癌风险计算器中使用的其他前列腺癌风险因素相加后的独立诊断价值。我们还将比较PSA与非那雄胺联合治疗或替代PCPT风险计算器与其他新开发的前列腺癌生物标记物的性能，包括PCA3、[-2]ProPSA和TMPRSS2：ERG，并评估这些额外的前列腺癌生物标记物对PCPT风险计算器性能的独立预测价值。该项目的长期目标是开发一种新的方法来改进前列腺癌的检测，同时减少不必要的前列腺活检的数量，这些程序与相当高的成本以及包括感染和出血在内的潜在风险相关。

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.