Abstract

BACKGROUND:

Hematuria is the most frequent presenting symptom in the vast majority of bladder cancer (BC) patients. The current recommended evaluation of hematuria includes cross sectional imaging and cystoscopy with possible high negative results, expensive costs and substantial patient burden.

OBJECTIVES:

To validate novel urine-based RNA-dependant tests; Xpert test and urinary metabolomics assay (CRAT and SLC 25A20genes expression) for BC detection in patients with hematuria.

METHODS:

Patients presented with hematuria to our tertiary care hospital were evaluated by CT urogram and office white light cystoscopy with subsequent inpatient biopsy for positive findings. Voided precystoscopy urine samples were prospectively collected. Xpert test, assay of targeted urinary metabolomics and cytology, were performed. The tests characteristics presumably were calculated based on the ability to identify BC noninvasively.

RESULTS:

Between March 2018 and June 2019, 181 patients were included in the final analysis with median (range) age 62 (10) years with 168 (92.8%) males. Macroscopic hematuria was encountered in 153 (84.5%) patients with irritative bladder symptoms in 48 (26.5%) patients. BC was confirmed by cystoscopy/biopsy in 36 (19.9%) patients. The performance characteristics of Xpert alone (SN: 73%, SP: 83%, NPV: 92%, PPV: 52%) (AUC 0.84, 95% CI 0.75– 0.93, p = 0.001), metabolomics assay alone (SN: 89%, SP: 93%, NPV: 97%, PPV: 78%) (AUC 0.91, 95% CI 0.85– 0.98, p < 0.001) and combination of both test results (SN: 66%, SP: 98%, NPV: 92%, PPV: 97%) (AUC 0.83, 95% CI 0.74– 0.93, p = 0.001) were notably superior to urine cytology (SN: 30%, SP: 84%, NPV: 83%, PPV: 33%) (AUC 0.58, 95% CI 0.47– 0.69, p = 0.154) for BC prediction. Cystoscopy-negative patients (CNP) were followed-up for a median (range) 12 (2– 19) months. Re-cystoscopy was done for 35 patients with persistent symptoms. BC was diagnosed in 6 patients. Xpert and urinary metabolomics results were observably positive in those 6 patients.

CONCLUSION:

Xpert test and assay of urinary metabolomics (CRAT and SLC 25A20 genes expression) have the potential for BC detection in hematuria patients. These non invasive urine based tests can help prioritization of the use of invasive diagnostic tests in systems with long waiting times.

中文翻译：

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新型基于尿液的mRNA检测（Xpert和尿液代谢组学标记测定）对血尿患者膀胱癌检测的诊断性能

摘要

背景：

在绝大多数膀胱癌（BC）患者中，血尿是最常见的症状。当前推荐的血尿评估包括横截面成像和膀胱镜检查，可能产生较高的阴性结果，昂贵的费用和大量患者负担。

目标：

验证新型的基于尿液的RNA依赖性检测；Xpert试验和尿液代谢组学分析（CRAT和SLC 25A20基因表达）可用于血尿患者的BC检测。

方法：

在我们的三级医院就诊的有血尿的患者通过CT尿路造影和办公室白光膀胱镜检查进行了评估，随后进行了活检，以寻找阳性结果。前瞻性地收集了无效的膀胱镜检查尿液样本。进行了Xpert测试，靶向尿代谢组学和细胞学检测。估计的测试特征是根据无创识别BC的能力计算得出的。

结果：

在2018年3月至2019年6月之间，纳入最终分析的181位患者的中位（范围）年龄为62（10）岁，男性168位（92.8％）。153名（84.5％）的患者出现了肉眼血尿，其中48名（26.5％）的患者出现了膀胱刺激性症状。通过膀胱镜检查/活检证实了36名（19.9％）患者的BC。仅Xpert的性能特征（SN：73％，SP：83％，NPV：92％，PPV：52％）（AUC 0.84，95％CI 0.75– 0.93，p  = 0.001），单独的代谢组学测定（SN：89 ％，SP：93％，NPV：97％，PPV：78％）（AUC 0.91、95％CI 0.85-0.98，p  <0.001）和两种测试结果的组合（SN：66％，SP：98％，NPV ：92％，PPV：97％）（AUC 0.83，95％CI 0.74–0.93，p BC  = 0.001）显着优于尿细胞学检查（SN：30％，SP：84％，NPV：83％，PPV：33％）（AUC 0.58，95％CI 0.47 – 0.69，p = 0.154）。膀胱镜检查阴性患者（CNP）进行了中位（范围）12（2-19）个月的随访。35例持续症状的患者进行了再次膀胱镜检查。BC被诊断为6例患者。Xpert和尿液代谢组学结果在这6例患者中均观察到阳性。

结论：

Xpert检测和尿液代谢组学分析（CRAT和SLC 25A20基因表达）可能在血尿患者中进行BC检测。这些基于非侵入性尿液的测试可以帮助在等待时间较长的系统中确定使用侵入性诊断测试的优先级。