title: A Prospective Blinded Evaluation of Urine-DNA Testing for Detection of Urothelial Bladder Carcinoma in Patients with Gross Hematuria.
abstract: Retrospective studies have provided proof of principle that bladder cancer can be detected by testing for the presence of tumor DNA in urine. We have conducted a prospective blinded study to determine whether a urine-based DNA test can replace flexible cystoscopy in the initial assessment of gross hematuria. A total of 475 consecutive patients underwent standard urological examination including flexible cystoscopy and computed tomography urography, and provided urine samples immediately before (n=461) and after (n=444) cystoscopy. Urine cells were collected using a filtration device and tested for eight DNA mutation and methylation biomarkers. Clinical evaluation identified 99 (20.8%) patients with urothelial bladder tumors. With this result as a reference and based on the analysis of all urine samples, the DNA test had a sensitivity of 97.0%, a specificity of 76.9%, a positive predictive value of 52.5%, and a negative predictive value of 99.0%. In three patients with a positive urine-DNA test without clinical evidence of cancer, a tumor was detected at repeat cystoscopy within 16 mo. Our results suggest that urine-DNA testing can be used to identify a large subgroup of patients with gross hematuria in whom cystoscopy is not required.
  
  
  
  We tested the possibility of using a urine-based DNA test to check for bladder cancer in patients with visible blood in the urine. Our results show that the test efficiently detects bladder cancer and therefore may be used to greatly reduce the number of patients who would need to undergo cystoscopy.
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Christina M
authors.initials: CM
authors.lastname: Dahmcke
authors.affiliation: Department of Urology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Steven
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Louise K
authors.initials: LK
authors.lastname: Larsen
authors.affiliation: Kirurgisk Urologisk Klinik, Rødovre, Denmark.
authors.forename: Asger L
authors.initials: AL
authors.lastname: Poulsen
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Abdul-Al
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Dahl
authors.affiliation: Danish Cancer Society Research Center, Copenhagen, Denmark. Electronic address: perg@cancer.dk.
authors.forename: Per
authors.initials: P
authors.lastname: Guldberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D003558:Cystoscopy; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D006417:Hematuria / Q000209:etiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014057:Tomography, X-Ray Computed; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine; D014556:Urine / Q000166:cytology*; D014567:Urography; D055815:Young Adult
keywords: Bladder cancer; DNA methylation; Driver mutations; Droplet digital PCR; Noninvasive detection; Urinary biomarkers; Urine filtration; Urothelial carcinoma