Abstract
BackgroundDue to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with bladder cancer. The identification of multiplex molecular signatures associated with disease has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis and monitoring.MethodsTo evaluate the performance of Oncuria™, a multiplex immunoassay for bladder detection in voided urine samples. The test was evaluated in a multi-institutional cohort of 362 prospectively collected subjects presenting for bladder cancer evaluation. The parallel measurement of 10 biomarkers (A1AT, APOE, ANG, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA) was performed in an independent clinical laboratory. The ability of the test to identify patients harboring bladder cancer was assessed. Bladder cancer status was confirmed by cystoscopy and tissue biopsy. The association of biomarkers and demographic factors was evaluated using linear discriminant analysis (LDA) and predictive models were derived using supervised learning and cross-validation analyses. Diagnostic performance was assessed using ROC curves.ResultsThe combination of the 10 biomarkers provided an AUROC 0.93 [95% CI 0.87–0.98], outperforming any single biomarker. The addition of demographic data (age, sex, and race) into a hybrid signature improved the diagnostic performance AUROC 0.95 [95% CI 0.90–1.00]. The hybrid signature achieved an overall sensitivity of 0.93, specificity of 0.93, PPV of 0.65 and NPV of 0.99 for bladder cancer classification. Sensitivity values of the diagnostic panel for high-grade bladder cancer, low-grade bladder cancer, MIBC and NMIBC were 0.94, 0.89, 0.97 and 0.93, respectively.ConclusionsUrinary levels of a biomarker panel enabled the accurate discrimination of bladder cancer patients and controls. The multiplex Oncuria™ test can achieve the efficient and accurate detection and monitoring of bladder cancer in a non-invasive patient setting.
Highlights
Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with bladder cancer
The current primary diagnostic approach to bladder cancer is cystoscopy coupled with voided urine cytology (VUC)
In a series of previous studies, we have identified a panel of urine-based protein biomarkers that are significantly associated with bladder cancer [8,9,10,11]
Summary
Urine-based assays currently have a limited role in the management of patients with bladder cancer. Methods: To evaluate the performance of OncuriaTM, a multiplex immunoassay for bladder detection in voided urine samples. The ability of the test to identify patients harboring bladder cancer was assessed. Given the complexity of the molecular changes involved in the development of neoplastic disease, a necessary shift from the use of single diagnostic biomarkers to molecular signatures for patient evaluation. The current primary diagnostic approach to bladder cancer is cystoscopy coupled with voided urine cytology (VUC). VUC remains the method of choice for the noninvasive detection of bladder cancer. The development of an accurate diagnostic bladder cancer assay that could be applied to non-invasively obtained urine samples would benefit both patients and health care systems
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