Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic , Cleveland , Ohio.
Cleveland Diagnostics, Inc. , Cleveland , Ohio.
J Urol. 2019 Jun;201(6):1115-1120. doi: 10.1097/JU.0000000000000185.
Current prostate specific antigen markers to detect prostate cancer are limited by low specificity for high grade disease. IsoPSA™ is a blood based, structure focused assay which predicts risk by partitioning the isoforms of prostate specific antigen that are linked to cancer in an aqueous 2-phase reagent system. We validated the clinical performance of this assay for identifying high grade disease in a new contemporary biopsy cohort.
We performed a multicenter prospective validation in 271 men scheduled for prostate biopsy at a total of 7 academic and community centers who were enrolled between May 2017 and March 2018. Blood samples were obtained for assay prior to biopsy. The discrimination power of the assay to detect high grade prostate cancer (Gleason 7 or greater) was evaluated by ROC analysis and compared to prior results. Clinical performance was further improved by comparison with multiparametric magnetic resonance imaging-ultrasound vs transrectal ultrasound guided biopsies.
The assay AUC was 0.784 for high grade vs low grade cancer/benign histology, which was superior to the AUCs of total prostate specific antigen and percent free prostate specific antigen. If 1,000 patients were biopsied, the assay would have reduced the number of unnecessary biopsies from 705 to 402 (43%) with only 22 missed high grade cancers, of which 7 would have been Gleason sum 4 + 3 or higher. Subset analysis of multiparametric magnetic resonance imaging guided biopsy produced a substantial improvement of the AUC to 0.831.
Validation of the structure based IsoPSA assay demonstrated statistical concordance with previously reported results and verified its superior performance vs concentration based prostate specific antigen and the free-to-total prostate specific antigen ratio. The assay improvement in detecting high grade prostate cancer using multiparametric magnetic resonance imaging-ultrasound guided biopsy may help define a new diagnostic paradigm.
目前用于检测前列腺癌的前列腺特异性抗原标志物的特异性较低，无法检测到高级别疾病。IsoPSA™ 是一种基于血液的结构分析检测方法，通过在水相 2 相试剂系统中对与癌症相关的前列腺特异性抗原同工型进行分区，预测风险。我们在一个新的当代活检队列中验证了该检测方法对识别高级别疾病的临床性能。
我们在 2017 年 5 月至 2018 年 3 月期间，在 7 个学术和社区中心共对 271 名计划进行前列腺活检的男性进行了多中心前瞻性验证。在活检前采集血液样本进行检测。通过 ROC 分析评估该检测方法对检测高级别前列腺癌（Gleason 7 或更高）的区分能力，并与以往结果进行比较。通过与多参数磁共振成像-超声与经直肠超声引导活检比较，进一步提高了临床性能。
该检测方法对高级别与低级别癌症/良性组织学的 AUC 为 0.784，优于总前列腺特异性抗原和游离前列腺特异性抗原百分比。如果对 1000 名患者进行活检，该检测方法可将不必要的活检数量从 705 例减少至 402 例（43%），仅漏诊 22 例高级别癌症，其中 7 例为 Gleason 评分 4+3 或更高。多参数磁共振成像引导活检的亚组分析将 AUC 提高到 0.831。
结构基础 IsoPSA 检测方法的验证表明与先前报道的结果具有统计学一致性，并验证了其相对于基于浓度的前列腺特异性抗原和游离/总前列腺特异性抗原比值的优越性能。使用多参数磁共振成像-超声引导活检检测高级别前列腺癌的检测方法的改进可能有助于定义新的诊断模式。
