title: A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria.
abstract: OBJECTIVE
  We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification.
  
  
  METHODS
  A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy. The sensitivity and specificity of the RNA tests were compared to cytology and the NMP22 assays using cystoscopy as the reference. The ability of Cxbladder to distinguish between low grade, stage Ta urothelial carcinoma and more advanced urothelial carcinoma was also determined.
  
  
  RESULTS
  uRNA detected 41 of 66 urothelial carcinoma cases (62.1% sensitivity, 95% CI 49.3-73.8) compared with NMP22 ELISA (50.0%, 95% CI 37.4-62.6), BladderChek (37.9%, 95% CI 26.2-50.7) and cytology (56.1%, 95% CI 43.8-68.3). Cxbladder, which was developed on the study data, detected 82%, including 97% of the high grade tumors and 100% of tumors stage 1 or greater. The cutoffs for uRNA and Cxbladder were prespecified to give a specificity of 85%. The specificity of cytology was 94.5% (95% CI 91.9-96.5), NMP22 ELISA 88.0%, (95% CI 84.6-91.0) and BladderChek 96.4% (95% CI 94.2-98.0). Cxbladder distinguished between low grade Ta tumors and other detected urothelial carcinoma with a sensitivity of 91% and a specificity of 90%.
  
  
  CONCLUSIONS
  uRNA and Cxbladder showed improved sensitivity for the detection of urothelial carcinoma compared to the NMP22 assays. Stratification with Cxbladder provides a potential method to prioritize patients for the management of waiting lists.
authors: Pacific Edge Ltd, Dunedin, New Zealand.
authors: Paul
authors: P
authors: O'Sullivan
authors: Katrina
authors: K
authors: Sharples
authors: Mark
authors: M
authors: Dalphin
authors: Peter
authors: P
authors: Davidson
authors: Peter
authors: P
authors: Gilling
authors: Lisa
authors: L
authors: Cambridge
authors: Justin
authors: J
authors: Harvey
authors: Tumi
authors: T
authors: Toro
authors: Nardia
authors: N
authors: Giles
authors: Carthika
authors: C
authors: Luxmanan
authors: Cris Felipe
authors: CF
authors: Alves
authors: Han-Seung
authors: HS
authors: Yoon
authors: Victoria
authors: V
authors: Hinder
authors: Jonathan
authors: J
authors: Masters
authors: Andrew
authors: A
authors: Kennedy-Smith
authors: Tony
authors: T
authors: Beaven
authors: Parry J
authors: PJ
authors: Guilford
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D005260:Female; D006417:Hematuria / Q000209:etiology / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D011446:Prospective Studies; D012313:RNA / Q000652:urine*; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine*; D014556:Urine / Q000166:cytology
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22; D012313:RNA