四激肽酶 panel 和 β-微 Seminoprotein 在前列腺穿刺活检预测高级别前列腺癌中的应用：芬兰参与的欧洲前列腺癌筛查随机研究的独立验证。
A Four-kallikrein Panel and β-Microseminoprotein in Predicting High-grade Prostate Cancer on Biopsy: An Independent Replication from the Finnish Section of the European Randomized Study of Screening for Prostate Cancer.
机构信息
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Prostate Cancer Research Center, Institute of Biosciences and Medical Technology, University of Tampere, Tampere, Finland; Fimlab Laboratories, Tampere University Hospital, Tampere, Finland.
出版信息
Eur Urol Focus. 2019 Jul;5(4):561-567. doi: 10.1016/j.euf.2017.11.002. Epub 2017 Nov 11.
BACKGROUND
A panel of four kallikrein markers (total, free, and intact prostate-specific antigen [PSA] and human kallikrein-related peptidase 2 [hK2]) improves predictive accuracy for Gleason score ≥7 (high-grade) prostate cancer among men biopsied for elevated PSA. A four-kallikrein panel model was originally developed and validated by the Dutch center of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The kallikrein panel is now commercially available as 4Kscore™.
OBJECTIVE
To assess whether these findings could be replicated among participants in the Finnish section of ERSPC (FinRSPC) and whether β-microseminoprotein (MSP), a candidate prostate cancer biomarker, adds predictive value.
DESIGN, SETTING, AND PARTICIPANTS: Among 4861 biopsied screening-positive participants in the first three screening rounds of FinRSPC, a case-control subset was selected that included 1632 biopsy-positive cases matched by age at biopsy to biopsy-negative controls.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
The predictive accuracy of prespecified prediction models was compared with biopsy outcomes.
RESULTS AND LIMITATIONS
Among men with PSA of 4.0-25ng/ml, 1111 had prostate cancer, 318 of whom had high-grade disease. Total PSA and age predicted high-grade cancer with an area under the curve of 0.648 (95% confidence interval [CI] 0.614-0.681) and the four-kallikrein panel increased discrimination to 0.746 (95% CI 0.717-0.774). Adding MSP to the four-kallikrein panel led to a significant (Wald test; p=0.015) but small increase (0.003) in discrimination. Limitations include a risk of verification bias among men with PSA of 3.0-3.99ng/ml and the absence of digital rectal examination results.
CONCLUSIONS
These findings provide additional evidence that kallikrein markers can be used to inform biopsy decision-making. Further studies are needed to define the role of MSP.
PATIENT SUMMARY
Four kallikrein markers and β-microseminoprotein in blood improve discrimination of high-grade prostate cancer at biopsy in men with elevated prostate-specific antigen.
背景
一组四项激肽释放酶标志物（总激肽释放酶、游离激肽释放酶、完整前列腺特异性抗原[PSA]和人激肽释放酶相关肽酶 2[hK2]）可提高因 PSA 升高而接受活检的男性中 Gleason 评分≥7（高级别）前列腺癌的预测准确性。该四项激肽释放酶标志物模型最初由荷兰的欧洲前列腺癌筛查随机研究中心（ERSPC）开发和验证。该激肽释放酶标志物面板现在作为 4Kscore™ 商业化。
目的
评估这些发现是否可以在 ERSPC 的芬兰部分（FinRSPC）参与者中得到复制，以及β-微 Seminoprotein（MSP）作为候选前列腺癌生物标志物是否具有预测价值。
设计、地点和参与者：在 FinRSPC 的前三个筛查轮次中，对 4861 名筛查阳性的参与者进行了活检，选择了一个病例对照亚组，该亚组包括 1632 名经活检证实为阳性的病例，按照活检时的年龄与经活检证实为阴性的对照组相匹配。
测量和统计分析
比较了预先指定的预测模型的预测准确性与活检结果。
结果和局限性
在 PSA 为 4.0-25ng/ml 的男性中，有 1111 人患有前列腺癌，其中 318 人患有高级别疾病。总 PSA 和年龄对高级别癌症的预测曲线下面积为 0.648（95%置信区间[CI] 0.614-0.681），而四项激肽释放酶标志物将诊断能力提高至 0.746（95%CI 0.717-0.774）。将 MSP 添加到四项激肽释放酶标志物面板中会导致明显（Wald 检验；p=0.015）但较小的（0.003）诊断能力提高。局限性包括 PSA 为 3.0-3.99ng/ml 的男性中存在验证偏倚风险，以及缺乏直肠指检结果。
结论
这些发现进一步证明了激肽释放酶标志物可用于辅助活检决策。需要进一步的研究来确定 MSP 的作用。
患者总结
在 PSA 升高的男性中，血液中的四项激肽释放酶标志物和β-微 Seminoprotein 可提高高级别前列腺癌的活检诊断能力。
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