title: Outcomes of a bladder cancer screening program using home hematuria testing and molecular markers.
abstract: BACKGROUND
  We previously reported the preliminary findings from a feasibility study of bladder cancer (BCa) screening with urinary molecular markers (Bladder Cancer Urine Marker Project [BLU-P]) that has now been terminated.
  
  
  OBJECTIVE
  To report the final results from BLU-P to determine whether mass screening for BCa is feasible and useful.
  
  
  METHODS
  BLU-P was a Dutch population-based study initiated in 2008 to evaluate BCa screening. A total of 6500 men were invited to participate in the study, 1984 (30.5%) agreed, and 1747 (88.1%) men completed the protocol and were followed for 2 yr.
  
  
  METHODS
  The screening protocol included home hematuria testing followed by molecular markers-nuclear matrix protein 22 (NMP22), microsatellite analysis (MA), fibroblast growth factor receptor 3 (FGFR3) mutation snapshot assay, and a custom methylation-specific (MLPA) test-to determine the need for cystoscopy.
  
  
  METHODS
  Outcomes included the number of cystoscopies and the cancer detection rate within and outside the protocol, as determined by linkage to national registries.
  
  
  CONCLUSIONS
  Overall, 409 men (23.4%) tested positive for hematuria and underwent molecular testing. Current smokers (n=295 [17%]) and past smokers (n=998 [58%]) were significantly more likely to test positive for hematuria than nonsmokers. Seventy-one of 75 men (94.6%) with positive molecular markers underwent the recommended cystoscopy. Four BCas and one kidney tumor were detected through this sequential protocol, whereas one BCa and one kidney tumor were missed through the screening program. Limitations include the possibility of healthy subject bias.
  
  
  CONCLUSIONS
  For BCa screening, use of a sequential protocol with home hematuria testing followed by molecular markers substantially reduced the number of cystoscopy recommendations compared with dipstick testing alone. A sequential screening approach may help minimize unnecessary invasive follow-up testing, with very few missed cancers. Nevertheless, this mass screening program had a very low diagnostic yield in an unselected asymptomatic European male population.
authors.affiliation: Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Bangma
authors.forename: Stacy
authors.initials: S
authors.lastname: Loeb
authors.forename: Martijn
authors.initials: M
authors.lastname: Busstra
authors.forename: Xiaoye
authors.initials: X
authors.lastname: Zhu
authors.forename: Samira
authors.initials: S
authors.lastname: El Bouazzaoui
authors.forename: Jeanine
authors.initials: J
authors.lastname: Refos
authors.forename: Kirstin A
authors.initials: KA
authors.lastname: Van Der Keur
authors.forename: Stephen
authors.initials: S
authors.lastname: Tjin
authors.forename: Conja G A M
authors.initials: CG
authors.lastname: Franken
authors.forename: Geert J L H
authors.initials: GJ
authors.lastname: van Leenders
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Zwarthoff
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Roobol
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D016009:Chi-Square Distribution; D003558:Cystoscopy; D019175:DNA Methylation; D005240:Feasibility Studies; D005819:Genetic Markers; D005820:Genetic Testing / Q000295:instrumentation; D006417:Hematuria / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D006801:Humans; D008297:Male; D008403:Mass Screening / Q000295:instrumentation / Q000379:methods*; D053842:Microsatellite Instability; D008875:Middle Aged; D009426:Netherlands; D009687:Nuclear Proteins / Q000652:urine; D018579:Patient Selection; D011237:Predictive Value of Tests; D011379:Prognosis; D011934:Reagent Strips; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics; D012042:Registries; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012648:Self Care / Q000295:instrumentation; D019564:Unnecessary Procedures; D016482:Urinalysis / Q000295:instrumentation; D001749:Urinary Bladder Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000652:urine
chemical_list: D015415:Biomarkers; D005819:Genetic Markers; D009687:Nuclear Proteins; D011934:Reagent Strips; C100379:nuclear matrix protein 22; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3