目的:比较Uromonitor®(U-MonitorLda,波尔图,葡萄牙),检测突变原癌基因的多靶DNA测定(端粒酶逆转录酶[TERT],成纤维细胞生长因子受体3[FGFR-3],Kirsten大鼠肉瘤病毒癌基因同源物[KRAS]),尿细胞学检查在多中心真实世界环境中对膀胱尿路上皮癌(UCB)的基于尿液的诊断中。
方法:这个多中心,prospective,从2019年至2024年,在四个德国泌尿外科中心进行了双盲研究。我们评估了Uromonitor与尿细胞学相比在UCB患者队列和真实世界环境中的健康对照中的诊断性能。灵敏度,特异性,阳性预测值(PPV),负预测值(NPV),并测量了测试的准确性,除了多变量分析以评估个体原癌基因突变在检测UCB中的能力。生物统计样本大小被设计成实现10%的灵敏度差异。
结果:UCB患者占研究组的63.7%(339/532)。尿检显示出敏感性,特异性,PPV,NPV,准确度,曲线下面积为49.3%,93.3%,92.8%,51.1%,65.2%,和0.713%,分别。这些指标在灵敏度方面未显示出比尿细胞学的统计学优势(44.6%;P=0.316)。此外,附加测试参数的比较,以及各种敏感性分析中的比较,两次尿检之间没有显着差异。多变量logistic回归强调了阳性尿路监测器对检测UCB的显著预测价值(比值比[OR]9.03;P<0.001)。此外,TERT和FGFR-3的突变与UCB检测的高几率独立相关(OR分别为13.30和7.04),而KRAS突变不表现出预测能力。
结论:尽管采用了创新的方法,Uromonitor未能证实在这种现实世界中先前研究的预期结果。用于检测和监测UCB的最佳基于尿液的生物标志物的搜索仍在进行中。这项研究的结果突出了开发非侵入性诊断工具的复杂性,并强调了持续研究努力改进这些技术的重要性。
OBJECTIVE: To compare Uromonitor® (U-Monitor Lda, Porto, Portugal), a multitarget DNA assay that detects mutated proto-oncogenes (telomerase reverse transcriptase [TERT], fibroblast growth factor receptor 3 [FGFR-3], Kirsten rat sarcoma viral oncogene homologue [KRAS]), with urine cytology in the urine-based diagnosis of urothelial carcinoma of the bladder (UCB) within a multicentre real-world setting.
METHODS: This multicentre, prospective, double-blind study was conducted across four German urological centres from 2019 to 2024. We evaluated the diagnostic performance of Uromonitor compared to urine cytology in a cohort of patients with UCB and in healthy controls within a real-world setting. Sensitivity, specificity, positive-predictive value (PPV), negative-predictive value (NPV), and accuracy of the tests were measured, in addition to multivariate analyses to assess the ability of individual proto-oncogene mutations in detecting UCB. The biometric sample size was designed to achieve a 10% difference in sensitivity.
RESULTS: Patients with UCB comprised 63.7% (339/532) of the study group. Uromonitor showed a sensitivity, specificity, PPV, NPV, accuracy, and an area-under-the-curve of 49.3%, 93.3%, 92.8%, 51.1%, 65.2%, and 0.713%, respectively. These metrics did not demonstrate statistical superiority over urine cytology in terms of sensitivity (44.6%; P = 0.316). Moreover, the comparison of additional test parameters, as well as the comparison within various sensitivity analyses, yielded no significant disparity between the two urinary tests. Multivariate logistic regression underscored the significant predictive value of a positive Uromonitor for detecting UCB (odds ratio [OR] 9.03; P < 0.001). Furthermore, mutations in TERT and FGFR-3 were independently associated with high odds of UCB detection (OR 13.30 and 7.04, respectively), while KRAS mutations did not exhibit predictive capability.
CONCLUSIONS: Despite its innovative approach, Uromonitor fell short of confirming the superior results anticipated from previous studies in this real-world setting. The search for an optimal urine-based biomarker for detecting and monitoring UCB remains ongoing. Results from this study highlight the complexity of developing non-invasive diagnostic tools and emphasise the importance of continued research efforts to refine these technologies.