Large multicenter validation of urine RNA profile for urothelial carcinoma detection and surveillance

BACKGROUNDCurrent diagnosis and surveillance of bladder cancer rely on cystoscopy, which is invasive and user dependent. The urine mRNA panel, uRNAp, measures expression of 3 genes for identification of bladder cancer. Here we report validation of uRNAp for patients undergoing initial workup for suspected bladder cancer and surveillance for bladder cancer.METHODSUrine specimens were prospectively collected prior to cystoscopy at 2 health care systems from patients without (detection cohort) or with (surveillance cohort) a history of bladder cancer. RNA was isolated from urine sediment for RT-qPCR to determine roundabout guidance receptor 1, corticotropin releasing hormone, and insulin-like growth factor 2 expression and calculate the uRNAp bladder cancer probability score.RESULTSIn the detection cohort, 547 samples were collected from 529 patients. There were 123 new diagnoses of bladder cancer in the detection cohort, and uRNAp demonstrated 98% sensitivity and 51% specificity for identification of bladder cancer. In the surveillance cohort, 1,543 samples were collected from 447 patients with 286 recurrences. uRNAp demonstrated 94% overall sensitivity with 43% specificity and 99% sensitivity for high-grade recurrence. The receiver operating characteristic area under the curve was 0.92 in the detection and 0.81 in the surveillance cohort. uRNAp scores significantly increased with tumor size and grade.CONCLUSIONProspective validation of uRNAp demonstrated a strong potential clinical utility as a noninvasive adjunct to cystoscopy for management of bladder cancer. uRNAp may be a useful triage tool to defer or expedite cystoscopy for patients undergoing detection or surveillance of bladder cancer.FUNDINGDepartment of Veterans Affairs BLR&D Merit Review I01 BX004962 to JCL.