1 Clinical Laboratory, Catharina Hospital, Eindhoven, the Netherlands.
2 Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, the Netherlands.
Ann Clin Biochem. 2019 Mar;56(2):259-265. doi: 10.1177/0004563218822665. Epub 2019 Feb 24.
Prostate-specific antigen is the biochemical gold standard for the (early) detection and monitoring of prostate cancer. Interpretation of prostate-specific antigen is both dependent on the method and cut-off. The aim of this study was to examine the effect of method-specific differences and cut-off values in a national external quality assessment scheme (EQAS).
The Dutch EQAS for prostate-specific antigen comprised an annual distribution of 12 control materials. The results of two distributions were combined with the corresponding cut-off value. Differences between methods were quantified by simple linear regression based on the all laboratory trimmed mean. To assess the clinical consequence of method-specific differences and cut-off values, a clinical data-set of 1040 patients with an initial prostate-specific antigen measurement and concomitant conclusive prostate biopsy was retrospectively collected. Sensitivity and specificity for prostate cancer were calculated for all EQAS participants individually.
In the Netherlands, seven different prostate-specific antigen methods are used. Interestingly, 67% of these laboratories apply age-specific cut-off values. Methods showed a maximal relative difference of 26%, which were not reflected in the cut-off values. The largest differences were caused by the type of cut-off, for example in the Roche group the cut-off value differed maximal 217%. Clinically, a fixed prostate-specific antigen cut-off has a higher sensitivity than an age-specific cut-off (mean 89% range 86-93% versus 79% range 63-95%, respectively).
This study shows that the differences in cut-off values exceed the method-specific differences. These results emphasize the need for (inter)national harmonization/standardization programmes including cut-off values to allow for laboratory-independent clinical decision-making.
前列腺特异性抗原是（早期）检测和监测前列腺癌的生化金标准。对前列腺特异性抗原的解读既依赖于方法，也依赖于临界值。本研究旨在检查国家外部质量评估计划（EQAS）中方法特异性差异和临界值的影响。
荷兰前列腺特异性抗原 EQAS 包括每年分发 12 种对照材料。将两次分布的结果与相应的临界值结合起来。基于所有实验室修剪均值的简单线性回归来量化方法之间的差异。为了评估方法特异性差异和临界值的临床后果，回顾性收集了 1040 名初始前列腺特异性抗原测量和同时进行的结论性前列腺活检的临床数据集。为所有 EQAS 参与者单独计算前列腺癌的敏感性和特异性。
在荷兰，使用了七种不同的前列腺特异性抗原方法。有趣的是，这些实验室中有 67%应用了年龄特异性临界值。方法显示出最大的相对差异为 26%，而这些差异并没有反映在临界值中。最大的差异是由临界值的类型引起的，例如在罗氏组中，临界值的差异最大为 217%。临床上，固定的前列腺特异性抗原临界值比年龄特异性临界值具有更高的敏感性（平均值 89%，范围 86-93%与 79%，范围 63-95%）。
本研究表明，临界值的差异超过了方法特异性差异。这些结果强调需要（国际）协调/标准化计划，包括临界值，以实现独立于实验室的临床决策。
