title: Clinical comparison of noninvasive urine tests for ruling out recurrent urothelial carcinoma.
abstract: Patients with urothelial carcinoma (UC) undergo rigorous surveillance for recurrence. Noninvasive urine tests are not currently recommended by guideline panels owing to insufficient clinical benefit. The objective of this study was to prospectively compare the performance of the Cxbladder Monitor test to other commonly available urine markers and cytology for surveillance of patients with UC.
  
  
  
  A total of 1,036 urine samples were collected from 803 patients undergoing surveillance for UC. Of these, 1,016 samples were directly assessed using cytology, NMP22 Bladderchek and NMP22 enzyme-linked immunosorbent assay (ELISA), and the clinically validated Cxbladder Monitor test. An exploratory analysis was also performed comparing data from 157 samples where UroVysion fluorescence in situ hybridization analysis was performed locally.
  
  
  
  The sensitivity of Cxbladder Monitor (0.91) significantly outperformed cytology (0.22), NMP22 ELISA (0.26), and NMP22 BladderChek (0.11). The negative predictive value of Cxbladder Monitor was also superior at 0.96 compared with cytology (0.87), NMP22 ELISA (0.87), and NMP22 BladderChek (0.86). All false-negative results (n = 14) observed using Cxbladder Monitor were also negative for cytology, NMP22 ELISA, and NMP22 BladderChek. In the more limited set, UroVysion fluorescence in situ hybridization also had inferior sensitivity (0.33) and negative predictive value (0.92).
  
  
  
  The Cxbladder Monitor test significantly outperforms current Food and Drug Administration-approved urine-based monitoring tests, as well as cytology, in a large representative population undergoing surveillance for recurrent UC. This supports using Cxbladder Monitor as a confirmatory negative adjunct to cystoscopy or to justify postponing cystoscopic investigations in patients with a low risk of recurrence.
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: Paul
authors.initials: P
authors.lastname: OʼSullivan
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, Cornell University, New York, NY; Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Sharokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: Laimonis
authors.initials: L
authors.lastname: Kavalieris
authors.affiliation: Department of Psychological Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Frampton
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand; Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Parry
authors.initials: P
authors.lastname: Guilford
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: Carthika
authors.initials: C
authors.lastname: Luxmanan
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand. Electronic address: jimmy.suttie@pelnz.com.
authors.forename: James
authors.initials: J
authors.lastname: Suttie
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Henry
authors.initials: H
authors.lastname: Crist
authors.affiliation: Department of Urology, Weill Cornell Medical College, Cornell University, New York, NY.
authors.forename: Douglas
authors.initials: D
authors.lastname: Scherr
authors.affiliation: Delaware Valley Urology, Mount Laurel, NJ.
authors.forename: Scott
authors.initials: S
authors.lastname: Asroff
authors.affiliation: Premier Medical Group of the Hudson Valley, Poughkeepsie, NY.
authors.forename: Evan
authors.initials: E
authors.lastname: Goldfischer
authors.affiliation: Florida Urology Associates, Orlando, FL.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Thill
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Darling
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000652:urine*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000652:urine*; D012372:ROC Curve; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000652:urine*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarkers; Diagnostic techniques; Molecular diagnostic techniques; Urinary bladder neoplasms; Urologic neoplasms; Urological