Using Prostate Health Index and MRI in Combination for Cost-effectively Detecting High-Grade Prostate Cancer in Minorities

项目摘要 理由：PSA筛查检测到太多的低风险前列腺癌（PCas）， 前列腺活检（PB）。因此，需要针对侵袭性PCa提高特异性的新诊断测试。 前列腺健康指数（PHI）测量3种激肽释放酶亚型，并已在多个队列中得到验证， 欧洲和美国用于预测PB时Gleason分级≥3+4级具有临床意义（cs）的PCa。测试可以 预防30-58%的不必要的PB，代价是延迟或错过极少数高级别PCA的检测。 18前列腺多参数MRI（MP-MRI）同样有希望检测Gleason ≥3+4 PCA。8，18，19 来自英国的PROMIS研究导致不必要的PB减少了27%，几乎没有遗漏的癌症。 然而，这两种测试的低特异性仍然使一半以上的男性遭受不必要的PB。此外， 在黑人男性中验证，在西班牙裔中几乎没有验证，因此排除了对 在高风险和不断增长的人群中预测准确性。18我们的长期目标是经济有效地 减少PCa过度检测和不必要的前列腺活检。 简要描述：目的1是一项观察性研究，旨在确定单独使用PHI和MRI的有效阈值， 串联（即PHI +/- MP-MRI和MP-MRI+/-PHI）或并联（PHI和MRI）检测csPCa。目标2是一项研究 按种族确定最具成本效益的策略。目标3将评估MRI遗漏的csPCas 通过仔细的病理检查并突出遗漏的csPCa，以在MP-MRI上证实， 并没有出现在核磁共振成像上所有地区将被分配一个PIRADS评分。MRI上未观察到的csPC将 根据Gleason分级、肿瘤大小和囊外扩展进行表征。我们还将寻找其他 侵袭性特征，如粉刺坏死、筛状组织学、导管内癌、神经内分泌 分化，以及淋巴血管和神经周围浸润。我们将通过以下措施实现这些目标 具体目标： 1)单独、串联和平行使用PHI和MRI确定特异性最高的活检策略 最大限度地检测活检初治黑人和西班牙裔患者的临床显著前列腺癌 男子; 2A）比较用于在初始活检时检测Gleason ≥3+4 PCa的活检策略的成本; 2B）估计每种策略相对于所有男性活检的成本效果，作为每个Gleason的成本 检出≥3+4个PCa; 3)描述接受根治性乳房切除术的黑人和西班牙裔男性的MRI盲态病变。

PROJECT SUMMARY Rationale: PSA screening detects too many low risk prostate cancers (PCas) and subjects too many men to prostate biopsy (PB). Hence, new diagnostic tests with improved specificity for aggressive PCa are needed. Prostate Health Index (PHI) measures 3 kallikrein isoforms and has been validated in multiple cohorts in Europe and the US for prediction of Gleason grade ≥3+4 clinically significant (cs) PCa at PB. The test could prevent 30-58% of unnecessary PBs at a cost of deferring or missing detection of very few high-grade PCas.16- 18 Multi-parametric MRI of the prostate (MP-MRI) is similarly promising for detecting Gleason ≥3+4 PCa.8,18,19 The PROMIS study from the UK resulted in a 27% reduction in unnecessary PBs with few missed cancers.19 However, both tests low specificity still subjects over half of men to unnecessary PB. Moreover, there is limited validation in Black men and almost no validation in Hispanics, thus precluding meaningful estimates of predictive accuracy in a high-risk and a growing population.18 Our long-term goal is to cost-effectively reduce PCa over-detection and unnecessary prostate biopsies. Brief Description: Aim 1 is an observational study to identify effective thresholds of PHI and MRI used alone, in series (i.e. PHI +/- MP-MRI and MP-MRI+/-PHI) or in parallel (PHI & MRI) for detecting csPCa. Aim 2 is a study to determine the most cost-effective strategy by race. Aim 3 will assess the csPCas that were missed by MRI by careful pathologic review and highlighting the missed csPCa for corroboration on MP-MRI to see if they were truly not present on the MRI. All regions will be assigned a PIRADS Score. csPCas not seen on MRI will be characterized for Gleason grade, tumor size and extracapsular extension. We will also look for other aggressive features like comedonecrosis, cribriform histology, intraductal carcinoma, neuroendocrine differentiation, and lymphovascular and perineural invasion. We will address these objectives with the following Specific Aims: 1) Identify the biopsy strategies with highest specificity using PHI and MRI alone, in series, and in parallel to maximize the detection of clinically significant prostate cancer for biopsy-naïve Black and Hispanic men; 2A) Compare the costs of the biopsy strategies for the detection of Gleason ≥3+4 PCa at initial biopsy; 2B) Estimate the cost-effectiveness of each strategy relative to biopsying all men as the cost per Gleason ≥3+4 PCa detected; 3) Characterize the MRI-blind lesions in Blacks and Hispanics men undergoing radical prostatectomy.