背景:根据最近的美国泌尿外科协会(AUA)关于血尿的指南,患者被分层为低,中间,和尿路上皮癌(UC)的高风险。这些风险组是基于临床因素,不纳入基于尿液的肿瘤标志物。
目的:评估基于尿液的基因组检测是否能改善重新定义的血尿AUA风险分层。
方法:我们选择了具有完整生物标志物状态的患者,根据尿液DNA评估,来自先前收集的前瞻性荷兰血尿队列(n=838)。根据性别将患者分为AUA风险类别,年龄,血尿类型。生物标志物状态包括FGFR3、TERT、和HRAS基因,OTX1、ONECUT2和TWIST1基因的甲基化状态。
方法:主要终点是不同血尿风险组的诊断模型表现。进一步的分析使用Fagan列线图评估血尿亚组的测试前和测试后UC概率。
结论:总体而言,65例患者(7.8%)被归类为低风险,106(12.6%)作为中等风险,667(79.6%)为高风险。肉眼血尿的UC发病率差异显著(21%,98/457)和显微镜下血尿(4%,14/381)组(p<0.001)。所有癌症病例都属于高危人群,其中UC发生率为16.8%(112/667)。诊断模型的应用揭示了所有风险组之间的稳健表现(接收器工作特征曲线0.929-0.971下的面积)。根据评估的风险组,尿液检测阴性与0.3-2%的试验后UC概率相关,而尿液检测阳性与试验后UC概率为31-42%相关.
结论:本研究表明,基于尿液的基因组分析增加了血尿患者AUA指南分层的价值。对于尿检阴性的AUA低风险患者,安全地停止膀胱镜检查似乎是合理的。此外,对于AUA中危或高危且尿液检测阳性的患者,应加快评估。
结果:尿液中有血液(血尿)的患者可以归类为低,中间,或在他们的泌尿道患癌症的高风险。我们发现,使用基于尿液的基因检测可以提高预测哪些患者最有可能患有癌症的准确性。测试阴性的患者可能能够避免侵入性测试,而进一步的测试可以优先考虑阳性测试的患者。
According to the recent American Urological Association (AUA)
guideline on hematuria, patients are stratified into groups with low, intermediate, and high risk of urothelial carcinoma (UC). These risk groups are based on clinical factors and do not incorporate urine-based tumor markers.
To evaluate whether a urine-based genomic assay improves the redefined AUA risk stratification for hematuria.
We selected patients with complete biomarker status, as assessed on urinary DNA, from a previously collected prospective Dutch hematuria cohort (n = 838). Patients were stratified into the AUA risk categories on the basis of sex, age, and type of hematuria. Biomarker status included mutation status for the FGFR3, TERT, and HRAS genes, and methylation status for the OTX1, ONECUT2, and TWIST1 genes.
The primary endpoint was the diagnostic model performance for different hematuria risk groups. Further analyses assessed the pretest and post-test UC probability in the hematuria subgroups using a Fagan nomogram.
Overall, 65 patients (7.8%) were classified as low risk, 106 (12.6%) as intermediate risk, and 667 (79.6%) as high risk. The UC incidence differed significantly between the gross hematuria (21%, 98/457) and microscopic hematuria (4%, 14/381) groups (p < 0.001). All cancer cases were in the high-risk group, which had UC incidence of 16.8% (112/667). Application of the diagnostic model revealed robust performance among all risk groups (area under the receiver operating characteristic curve 0.929-0.971). Depending on the risk group evaluated, a negative urine assay was associated with post-test UC probability of 0.3-2%, whereas a positive urine assay was associated with post-test UC probability of 31-42%.
This study shows the value that a urine-based genomic assay adds to the AUA
guideline stratification for patients with hematuria. It seems justified to safely withhold cystoscopy for patients with AUA low risk who have a negative urine assay. In addition, evaluation should be expedited for patients with AUA intermediate or high risk and a positive urine assay.
Patients who have blood in their urine (hematuria) can be classified as having low, intermediate, or high risk of having cancer in their urinary tract. We found that use of a urine-based genetic test improves the accuracy of predicting which patients are most likely to have cancer. Patients with a negative test may be able to avoid invasive tests, while further tests could be prioritized for patients with a positive test.