Wojno Kirk J, Costa Frank J, Cornell Robert J, Small Jeffrey D, Pasin Erik, Van Criekinge Wim, Bigley Joseph W, Van Neste Leander
Director of Pathology at Comprehensive Urology, Royal Oak, MI.
Director at the Urology Institute of Pittsburgh, Monroeville, PA.
Am Health Drug Benefits. 2014 May;7(3):129-34.
The diagnosis of prostate cancer is dependent on histologic confirmation in biopsy core tissues. The biopsy procedure is invasive, puts the patient at risk for complications, and is subject to significant sampling errors. An epigenetic test that uses methylation-specific polymerase chain reaction to determine the epigenetic status of the prostate cancer-associated genes GSTP1, APC, and RASSF1 has been clinically validated and is used in clinical practice to increase the negative predictive value in men with no history of prostate cancer compared with standard histopathology. Such information can help to avoid unnecessary repeat biopsies. The repeat biopsy rate may provide preliminary clinical utility evidence in relation to this assay's potential impact on the number of unnecessary repeat prostate biopsies performed in US urology practices.
The purpose of this preliminary study was to quantify the number of repeat prostate biopsy procedures to demonstrate a low repeat biopsy rate for men with a history of negative histopathology who received a negative epigenetic assay result on testing of the residual prostate tissue.
In this recently completed field observation study, practicing urologists used the epigenetic test called ConfirmMDx for Prostate Cancer (MDxHealth, Inc, Irvine, CA) to evaluate cancer-negative men considered at risk for prostate cancer. This test has been previously validated in 2 blinded multicenter studies that showed the superior negative predictive value of the epigenetic test over standard histopathology for cancer detection in prostate biopsies. A total of 5 clinical urology practices that had ordered a minimum of 40 commercial epigenetic test requisitions for patients with previous, cancer-negative biopsies over the course of the previous 18 months were contacted to assess their interest to participate in the study. Select demographic and prostate-screening parameter information, as well as the incidence of repeat biopsy, specifically for patients with a negative test result, was collected and merged into 1 collective database. All men from each of the 5 sites who had negative assay results were included in the analysis.
A total of 138 patients were identified in these urology practices and were included in the analysis. The median age of the men was 63 years, and the current median serum prostate-specific antigen level was 4.7 ng/mL. Repeat biopsies had been performed in 6 of the 138 (4.3%) men with a negative epigenetic assay result, in whom no evidence of cancer was found on histopathology.
In this study, a low rate of repeat prostatic biopsies was observed in the group of men with previous histopathologically negative biopsies who were considered to be at risk for harboring cancer. The data suggest that patients managed using the ConfirmMDx for Prostate Cancer negative results had a low rate of repeat prostate biopsies. These results warrant a large, controlled, prospective study to further evaluate the clinical utility of the epigenetic test to lower the unnecessary repeat biopsy rate.
前列腺癌的诊断依赖于活检核心组织的组织学确认。活检程序具有侵入性，使患者面临并发症风险，且存在显著的取样误差。一种使用甲基化特异性聚合酶链反应来确定前列腺癌相关基因GSTP1、APC和RASSF1表观遗传状态的表观遗传学检测方法已得到临床验证，并在临床实践中用于提高与标准组织病理学相比无前列腺癌病史男性的阴性预测值。此类信息有助于避免不必要的重复活检。重复活检率可能为该检测方法对美国泌尿外科实践中不必要的重复前列腺活检数量的潜在影响提供初步的临床实用性证据。
本初步研究的目的是量化重复前列腺活检程序的数量，以证明对于组织病理学结果为阴性且残余前列腺组织检测表观遗传学检测结果为阴性的男性，其重复活检率较低。
在这项最近完成的现场观察研究中，执业泌尿科医生使用名为前列腺癌ConfirmMDx（MDxHealth公司，加利福尼亚州欧文市）的表观遗传学检测方法来评估被认为有前列腺癌风险的癌症阴性男性。该检测方法先前已在两项双盲多中心研究中得到验证，这两项研究表明，在前列腺活检中，表观遗传学检测在癌症检测方面的阴性预测值优于标准组织病理学。我们联系了5家临床泌尿外科诊所，这些诊所在过去18个月内为先前活检结果为癌症阴性的患者至少订购了40份商业表观遗传学检测申请，以评估他们参与研究的兴趣。收集了选定的人口统计学和前列腺筛查参数信息，以及重复活检的发生率，特别是检测结果为阴性的患者的发生率，并将其合并到一个综合数据库中。来自5个地点的所有检测结果为阴性的男性都纳入了分析。
在这些泌尿外科诊所共识别出138名患者并纳入分析。这些男性的中位年龄为63岁，当前中位血清前列腺特异性抗原水平为4.7 ng/mL。138名表观遗传学检测结果为阴性的男性中有6名（4.3%）进行了重复活检，组织病理学检查未发现癌症证据。
在本研究中，在先前组织病理学检查结果为阴性且被认为有患癌风险的男性群体中，观察到重复前列腺活检率较低。数据表明使用前列腺癌ConfirmMDx检测结果为阴性的患者重复前列腺活检率较低。这些结果值得进行一项大型、对照、前瞻性研究，以进一步评估表观遗传学检测降低不必要重复活检率的临床实用性。
