Department of Urology, Instituto Valenciano de Oncología, Valencia, Spain.
Department of Urology, IIS-Aragón, University Hospital Miguel Servet, Zaragoza, Spain.
Prostate. 2020 May;80(6):500-507. doi: 10.1002/pros.23964. Epub 2020 Feb 20.
A 2-gene urine-based molecular test that targets messenger RNAs known to be overexpressed in aggressive prostate cancer (PCa) has been described as a helpful method for detecting clinically significant prostate cancer (grade group [GG] ≥2). We performed an external validation of this test in men undergoing initial prostate biopsy (Bx) within a Spanish opportunistic screening scenario.
We analyzed archived samples from 492 men who underwent prostate Bx in an opportunistic screening scenario, with prostate-specific antigen (PSA) 3 to 10 ng/mL and/or suspicious digital rectal exploration (DRE) and without previous multi-parametric magnetic resonance imaging (mpMRI). Urinary biomarker measurements were combined with clinical risk factors to determine a risk score, and accuracy for GG ≥ 2 PCa detection was compared with PCA3, European randomized screening in prostate cancer (ERSPC), and prostate biopsy collaborative group (PBCG) risk calculators in a validation workup that included calibration, discrimination, and clinical utility analysis.
In our cohort, the detection rates for GG1 and GG ≥ 2 PCa were 20.3% and 14.0%, respectively. The median PSA level was 3.9 ng/mL and 13.4% of subjects had suspicious DRE findings. The median risk score for men with GG ≥ 2 PCa was 21 (interquartile range: 14-28), significantly higher than benign+GG1 PCa (10, 6-18), P < .001, achieving the highest area under the curve among the models tested, 0.749 (95% confidence interval: 0.690-0.807). The urine test was well-calibrated, while ERSPC showed a slight underestimation and PBCG a slight overestimation of risk. Assuming a GG2 non-detection rate of 11% without using mpMRI, use of the urinary biomarker-based clinical model could have helped avoid 37.2% of excess biopsies while delaying the diagnosis of eight patients (1.6% of the entire cohort) with GG ≥ 2 PCa.
In this first evaluation in an opportunistic screening population, the urinary biomarker-based test improved the detection of clinically significant PCa. Facing men with elevated PSA and/or suspicious DRE, it could be a useful tool to help avoid excess initial Bx and to identify patients most likely to benefit from Bx.
一种针对信使 RNA 的 2 基因尿液分子检测方法，该方法针对的是在侵袭性前列腺癌（PCa）中过度表达的信使 RNA，被描述为一种有助于检测临床上有意义的前列腺癌（GG≥2）的方法。我们在西班牙机会性筛查场景中对接受初始前列腺活检（Bx）的男性进行了该检测的外部验证。
我们分析了在机会性筛查场景中接受前列腺 Bx 的 492 名男性的存档样本，这些男性的前列腺特异性抗原（PSA）为 3 至 10ng/ml，且/或直肠指诊（DRE）可疑，且无先前的多参数磁共振成像（mpMRI）。尿液生物标志物测量结果与临床危险因素相结合，以确定风险评分，并将其与 PCA3、欧洲前列腺癌随机筛查（ERSPC）和前列腺活检协作组（PBCG）风险计算器进行比较，以进行验证工作，包括校准、区分度和临床实用性分析。
在我们的队列中，GG1 和 GG≥2 PCa 的检出率分别为 20.3%和 14.0%。中位 PSA 水平为 3.9ng/ml，13.4%的受试者有可疑的 DRE 发现。GG≥2 PCa 男性的中位风险评分中位数为 21（四分位距：14-28），明显高于良性+GG1 PCa（10，6-18），P<.001，在测试的模型中获得了最高的曲线下面积，0.749（95%置信区间：0.690-0.807）。尿液检测具有良好的校准性，而 ERSPC 显示风险略有低估，PBCG 显示风险略有高估。假设不使用 mpMRI 情况下 GG2 未检出率为 11%，则使用基于尿液生物标志物的临床模型可以帮助避免 37.2%的过度活检，同时延迟诊断 8 名 GG≥2 PCa 患者（整个队列的 1.6%）。
在机会性筛查人群中的首次评估中，基于尿液生物标志物的检测提高了临床上有意义的 PCa 的检出率。对于 PSA 升高和/或 DRE 可疑的男性，它可能是一种有用的工具，可以帮助避免过度的初始 Bx，并识别最有可能从 Bx 中获益的患者。
