LAUSR

BACKGROUND Current clinical guidelines recommend cystoscopy in patients who present with hematuria to rule out a bladder tumor. Here, we evaluated whether our previously developed urine assay was able to triage hematuria patients for cystoscopy in a large prospective cohort. MATERIALS AND METHODS A urine sample was collected prior to cystoscopy and mutation/methylation status of 6 genes was determined on cellular DNA. The existing diagnostic model was validated on this cohort. Logistic regression was applied to investigate other potential variables. Primary endpoint was the model performance, as indicated by the Area Under the Curve (AUC). Secondary endpoints were sensitivity, specificity and negative predictive value (NPV). Clinical usefulness was determined by the net benefit approach. RESULTS In 838 patients, biomarker status could be determined for all genes. Urothelial cancer was observed in 112 patients (98/457 in the gross and 14/381 in the microscopic hematuria group). Validation of the existing model resulted in an AUC of 0.93. Logistic regression analysis identified type of hematuria as a significant additional variable. Adding type of hematuria resulted in an AUC of 0.95 (96% sensitivity, 73% specificity, 99% NPV). The assay identified all upper tract tumors (n=6), not visible by cystoscopy. Net benefit analysis showed that the urine assay should be preferred over current clinical practice. Implementing the urine assay as a triage tool could lead to a 53% reduction in cystoscopies. CONCLUSIONS The urine assay detected urothelial cancer with a very high accuracy and can be used to triage patients presenting with hematuria for cystoscopy.