title: Combinations of urine-based tumour markers in bladder cancer surveillance.
abstract: OBJECTIVE
  The aim of the study was to investigate whether combinations of urine-based tumour markers including urinary cytology (Cytology or Cyt) increase the sensitivity in the detection of bladder cancer recurrence.
  
  
  METHODS
  Urinary cytology, NMP22, UroVysion (FISH) and ImmunoCyt (uCyt+) were determined in 221 patients during the follow-up of non-muscle-invasive transitional cell carcinoma (NMI TCC) before cystoscopy (n = 49) or with the suspicion of TCC recurrence before transurethral resection of the bladder (n = 173). For all markers alone as well as in all possible combinations (multimarker panels, MPs) sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were evaluated. MPs were considered positive if at least one marker was positive.
  
  
  RESULTS
  No malignancy was found in 108 patients, whereas recurrent TCC was confirmed in 113 patients. Sensitivity and specificity for Cytology were 84% and 62%, for NMP22 68% and 49%, for FISH 72% and 63%, and for uCyt+ 73% and 62%, respectively. The NPV was below 80% for all markers alone. Combinations of two and three markers increased the sensitivity as well as the NPV to over 90 and 80%, by reducing specificity to an average of 44% and 35%, respectively. The most sensitive combinations were NMP22, uCyt+ together with Cytology and FISH, and uCyt+ together with NMP22 (sensitivity for both combinations 98%). There was no further improvement when all four markers were combined.
  
  
  CONCLUSIONS
  Combinations of tumour markers increased the sensitivity and NPV in the detection of recurrence of NMI TCC. A stepwise approach of tumour marker determination may be used to reduce the frequency of follow-up cystoscopies at a reasonable risk.
authors.affiliation: Department of Urology, Eberhard Karls University Tuebingen, Tuebingen, Germany. marcushorstmann@gmx.ch
authors.forename: Marcus
authors.initials: M
authors.lastname: Horstmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Patschan
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.forename: Erika
authors.initials: E
authors.lastname: Senger
authors.forename: Gerhard
authors.initials: G
authors.lastname: Feil
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D009687:Nuclear Proteins / Q000652:urine*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000652:urine; D014556:Urine / Q000166:cytology*
chemical_list: D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; C100379:nuclear matrix protein 22