Diagnosing clinically-significant prostate cancer in African American men: Systematic random versus MR-image-fusion guided biopsy

 描述（由申请人提供）：大多数局限性前列腺癌（PCa）是惰性的，在患者的一生中永远不会变得具有侵袭性。这些患者中的许多人可以从主动监测（AS）中受益，但对他们个人风险的不确定性促使他们选择根治性椎间盘切除术（RP）或放射治疗，这可能对生活质量产生负面影响，在美国只有约10%的患者选择AS。阻止AS更广泛采用的关键障碍之一是，目前的12芯系统随机前列腺穿刺诊断活检（SR-Bx）方案可能会错过约30%患者中已经存在于前列腺中的更晚期疾病区域，从而在诊断时引入分期不足和分级不足的错误。这种错误似乎在非洲裔美国人（AA）男性中更高，他们患侵袭性PCa和死于这种疾病的风险更高。具体而言，在AA男性中，现有的确定AS资格的预测因子似乎表现得更差，活检期间遗漏的高级别肿瘤的比率更高，AS期间肿瘤进展的比率更高。因此，迫切需要测试更可靠的活检方法，以更好地区分具有临床意义的疾病（CiPCa）的男性，他们将真正受益于AS，与那些需要明确治疗的具有临床意义的PCa（CSPCa）。我们已经证明，在白色男性中，使用MRI识别可疑病变并使用MRI-US图像融合活检技术（MRUS-Bx）进行前列腺活检，在CSPCa检测、癌核长度、每个癌核的癌率、癌体积估计和前壁癌检测（在AA男性中更常见）方面优于SR-Bx。我们现在建议进行一项随机对照试验，比较AA和白色男性中SR-Bx和MRUS-Bx的CSPCa检出率，以提供更好的临床工具来区分CSPCa和CiSPCa，从而从长远来看，提高AA男性的总生存率。目标1：我们计划在5个学术机构和1个私人诊所招募400名PSA升高（>2.5 ng/mL）且直肠指检阴性的男性（200名AA，200名白色）。男性将被随机分为两组：1）SR-Bx（12个核心），对于没有CSPCa的男性，在活检后3个月进行MRI; 2）对于男性，在MRI可见病变（PIRADS > 3）时，进行活检前MRI，使用MRUS-Bx（2个核心/病变）。我们将比较CSPCa和CiSPCa的活检检出率。目标2：我们将在选择RP（RCT中约110例）的男性中验证MRUS-Bx的准确性，其基于与RP阶梯切片标本结果的一致性。目标3：我们将在受邀参与和入组RCT的男性中确定a）研究参与和B）治疗决策（AS vs放疗vs RP）的决定因素，以及c）比较SR-BX vs MRUS-BX相关的发病率。我们的研究结果可能会改变护理标准，提高无症状男性PCa诊断的准确性，这将增加做出正确治疗决定的信心（明确治疗与积极监测），特别是处于最不利地位的AA男性PCa。1

 DESCRIPTION (provided by applicant): Most localized prostate cancers (PCa) are indolent and will never become aggressive during a patient's lifetime. Many of these patients could benefit from active surveillance (AS), but uncertainty about their individual risk prompts them to choose radical prostatectomy (RP) or radiation therapy, which can negatively impact quality of life, with only ~10% of patients in the US electing AS. Among the key barriers that prevent a more widespread adoption of AS is the fact that the current 12-core systematic random prostate needle diagnostic biopsy (SR-Bx) protocol can miss areas of more advanced disease already present in the prostate in ~30% of patients, thus introducing under-staging and under-grading error at the time of diagnosis. This error seems to be higher among African-American (AA) men, who are at a disproportionally higher risk of developing aggressive PCa and of dying of their disease. Specifically, among AA men, existing predictors to determine AS eligibility seem to perform more poorly, the rate of high-grade tumors missed during biopsy is higher, and rates tumor progression while on AS are higher. Therefore, there is an urgent need to test more reliable biopsy approaches to better discriminate men with clinically insignificant disease (CiPCa), who will truly benefit from AS, from those with clinically significant PCa (CSPCa) who require definitive treatment. We have shown that among white men the use of MRI for identifying suspicious lesions and for targeting prostate biopsies to them with MRI-US image-fusion biopsy technique (MRUS-Bx) outperforms SR-Bx in CSPCa detection, cancer core length, cancer rate per core, cancer volume estimation, and detection of anterior cancers (more common among AA men). We now propose to undertake a randomized controlled trial to compare the detection rate of CSPCa between SR-Bx and MRUS-Bx among AA and white men, to provide better clinical tools to discriminate between CSPCa and CiSPCa and thus, in the long term, improve overall survival among AA men. AIM 1: We propose to enroll 400 men (200 AA, 200 white) with elevated PSA (>2.5 ng/mL) and negative digital rectal exam across 5 academic institutions and 1 private practice. Men will be randomized into two arms: 1) SR-Bx (12 cores) with an MRI 3-months after biopsy for men without CSPCa; 2) pre-biopsy MRI with MRUS- Bx (2 cores/lesion) for men MRI visible lesions (PIRADS > 3). We will compare biopsy detection rate of CSPCa and CiSPCa. AIM 2: we will validate among men who elect RP (~110 in the RCT) the accuracy of MRUS-Bx based on the agreement with findings from step-sectioned RP specimens. AIM 3: we will identify among men invited to participate and those enrolled in the RCT, determinants of a) study participation and b) treatment decision (AS vs radiation vs RP), and c) compare morbidity associated with either SR-Bx vs MRUS-Bx. The results of our study may change the standard of care and improve accuracy in the diagnosis of PCa among asymptomatic men, which will increase confidence in making the correct treatment decision (definitive treatment versus active surveillance), particularly AA men with PCa who are at the greatest disadvantage. 1