Introduction: Due to insufficient accuracy, urine-based assays currently have a limited role in the management of patients with upper tract urothelial cancers (UTUC). The application of a robust urine-based multiplex assay to aid in the diagnosis of UTUC has the potential to address this deficiency and to assist with accurate, non-invasive diagnosis. Methods: To evaluate the performance of Oncuria™- Detect, a multiplex immunoassay capable of querying a voided urine sample for 10 protein biomarkers associated with urothelial carcinoma A1AT, APOE, ANG, CA9, IL8, MMP9, MMP10, PAI1, SDC1 and VEGFA). Its application to UTUC was evaluated in a multi-institutional cohort of 31 prospectively collected subjects presenting for evaluation of upper tract mass along with 41 prospective collected matched controls (i.e., non-tumor bearing). The ability of the test to identify patients harboring UTUC was assessed. UTCU status was confirmed by endoscopy and tissue biopsy or definitive surgery. Diagnostic performance was assessed using ROC curves. Results: Oncuria™- Detect provided an AUC of 0.897 (95% CI: 0.817-0.977) with an overall sensitivity of 93.5%, specificity of 75.6%, NPV 93.9% and PPV 74.4%. Sensitivity values of the diagnostic panel for high-grade UTUC, low-grade UTUC, non-invasive UTUC and invasive UTUC were 88.9%, 92.3%, 86.7% and 100%, respectively. Urinary cytology or selective ureteral washing/cytology was associated with an overall sensitivity of 58.3%, specificity of 100%, NPV 79.2% and PPV 100%. Sensitivity values of cytology for high-grade UTUC, low-grade UTUC, non-invasive UTUC and invasive UTUC were 50%, 100%, 80% and 42.9%, respectively. Conclusions: Urinary levels of a biomarker panel enabled the accurate discrimination of UTUC and controls non-tumor bearing individuals. The multiplex Oncuria™-Detect test can achieve the efficient and accurate detection of UTUC in a non-invasive patient setting. SOURCE OF Funding: NIH/NCI R01CA198887 (CJR), UH3CA271377 (CJR), and R21CA263230 (HF).
