title: Stepwise application of urine markers to detect tumor recurrence in patients undergoing surveillance for non-muscle-invasive bladder cancer.
abstract: BACKGROUND
  The optimal use of urine markers in the surveillance of non-muscle-invasive bladder cancer (NMIBC) remains unclear. Aim of the present study was to investigate the combined and stepwise use of the four most broadly available urine markers to detect tumor recurrence in patients undergoing surveillance of NMIBC.
  
  
  METHODS
  483 patients with history of NMIBC were included. Cytology, UroVysion, fluorescence in situ hybridization (FISH), immunocytology (uCyt+), and NMP22 ELISA were performed before surveillance cystoscopy. Characteristics of single tests and combinations were assessed by contingency analysis.
  
  
  RESULTS
  128 (26.5%) patients had evidence of tumor recurrence. Sensitivities and negative predictive values (NPVs) of the single tests ranged between 66.4-74.3 and 82.3-88.2%. Two-marker combinations showed sensitivities and NPVs of 80.5-89.8 and 89.5-91.2%. A stepwise application of the two-test combinations with highest accuracy (cytology and FISH; cytology and uCyt+; uCyt+ and FISH) showed NPVs for high-risk recurrences (G3/Cis/pT1) of 98.8, 98.8, and 99.1%, respectively.
  
  
  CONCLUSIONS
  Combinations of cytology, FISH, immunocytology, and NMP22 show remarkable detection rates for recurrent NMIBC. Stepwise two-test combinations of cytology, FISH, and immunocytology have a low probability of missing a high-risk tumor. The high sensitivities may justify the use of these combinations in prospective studies assessing the use of urine markers to individualize intervals between cystoscopies during follow-up.
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany ; V6H 3Z6 Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada V6H 3Z6.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Esser
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mohrhardt
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Aufderklamm
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Böttge
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rausch
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Mischinger
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Simone
authors.identifier: 0000-0003-0189-1119
authors.initials: S
authors.lastname: Bier
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kuehs
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Arnulf
authors.identifier: 0000-0003-4207-9928
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, Eberhard-Karls University, Hoppe-Seyler Strasse 3, 72076 Tübingen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Schwentner
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000652:urine*; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor