title: Screening for bladder cancer with urinary tumor markers in chemical workers with exposure to aromatic amines.
abstract: OBJECTIVE
  To validate urinary markers for the early detection of bladder cancer (BC) in chemical workers.
  
  
  METHODS
  UroScreen was conducted as a validation study for tumor markers within the frame of a health surveillance program of the German Social Accident Insurance for active or retired workers with former exposure to aromatic amines. From 2003 to 2010, 1,609 men took part in voluntary annual screens. Cytology, the quantitative NMP22(®) assay, and UroVysion™ were applied to 7,091 urine samples.
  
  
  RESULTS
  Fifteen out of 21 tumors were detected following test positivity. The UroVysion/NMP22 panel detected 14 out of 21 tumors versus 8 tumors with cytology alone (sensitivity 66.7 vs. 44.4 %, specificity 94.5 vs. 98.5 %). The sensitivity of the panel increased to 85.7 % in samples collected ≤12 months before diagnosis and when papillomas were excluded, compared to 58.3 % with cytology. About 3 % of NMP22 tests were false-positive. UroVysion results overlapped with cytology due to the preselection of atypical cells. NMP22 was less and UroVysion more frequently positive in diluted urine samples. Leukocytes confounded NMP22 but not UroVysion. The low incidence of BC in this study population yielded low positive predictive values of the markers and high costs per tumor detected with screening.
  
  
  CONCLUSIONS
  UroVysion in combination with NMP22 detected more cases than cytology alone, at the expense of a lower specificity. High costs per detected case resulted from a lower BC incidence than in the past when levels of occupational exposure to aromatic amines were higher. Currently, it cannot be recommended to apply these markers for screening in asymptomatic workers. The increase in sensitivity is not balanced by the high costs of UroVysion and the false-positive tests of NMP22.
authors.affiliation: Institute for Prevention and Occupational Medicine of the German Social Accident Insurance, Institute of the Ruhr-Universität Bochum (IPA), Buerkle-de-la-Camp-Platz 1, 44789, Bochum, Germany, pesch@ipa-dguv.de.
authors.forename: Beate
authors.initials: B
authors.lastname: Pesch
authors.forename: Dirk
authors.initials: D
authors.lastname: Taeger
authors.forename: Georg
authors.initials: G
authors.lastname: Johnen
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gawrych
authors.forename: Nadine
authors.initials: N
authors.lastname: Bonberg
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
authors.forename: Harald
authors.initials: H
authors.lastname: Wellhäusser
authors.forename: Matthias
authors.initials: M
authors.lastname: Kluckert
authors.forename: Gabriele
authors.initials: G
authors.lastname: Leng
authors.forename: Michael
authors.initials: M
authors.lastname: Nasterlack
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.forename: Thomas
authors.initials: T
authors.lastname: Brüning
mesh_terms: D000328:Adult; D000368:Aged; D000588:Amines / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000652:urine*; D016273:Occupational Exposure / Q000032:analysis*; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*
chemical_list: D000588:Amines; D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22