title: Prognostic relevance of positive urine markers in patients with negative cystoscopy during surveillance of bladder cancer.
abstract: BACKGROUND
  The role of urine markers in the surveillance of patients with non-muscle invasive bladder cancer (NMIBC) is discussed extensively. In case of negative cystoscopy the additional prognostic value of these markers has not been clearly defined yet. The present study is the first systematic approach to directly compare the ability of a urine marker panel to predict the risk of recurrence and progression in bladder cancer (BC) patients with no evidence of relapse during surveillance for NMIBC.
  
  
  METHODS
  One hundred fourteen patients who underwent urine marker testing during surveillance for NMIBC and who had no evidence of BC recurrence were included. For all patients cytology, Fluorescence-in-situ-hybridization (FISH), immunocytology (uCyt+) and Nuclear matrix protein 22 enzyme-linked immunosorbent assay (NMP22) were performed. All patients completed at least 24 months of endoscopic and clinical follow-up of after inclusion.
  
  
  RESULTS
  Within 24 months of follow-up, 38 (33.0%) patients experienced disease recurrence and 11 (9.8%) progression. Recurrence rates in patients with positive vs. negative cytology, FISH, uCyt+ and NMP22 were 52.6% vs. 21.9% (HR = 3.9; 95% CI 1.75-9.2; p < 0.001), 47.6% vs. 25.0% (HR 2.7; 1.2-6.2; p = 0.01), 43.8% vs. 22.4% (HR 3.3; 1.5-7.6; p = 0.003) and 43.8% vs. 16.7% (HR 4.2; 1.7-10.8; p = 0.001). In patients with negative cytology, a positive NMP22 test was associated with a shorter time to recurrence (p = 0.01), whereas FISH or uCyt+ were not predictive of recurrence in these patients. In the group of patients with negative cytology and negative NMP22, only 13.5% and 5.4% developed recurrence and progression after 24 months.
  
  
  CONCLUSIONS
  Patients with positive urine markers at time of negative cystoscopy are at increased risk of recurrence and progression. In patients with negative cytology, only NMP22 is predictive for recurrence. Patients with negative marker combinations including NMP22 harbour a low risk of recurrence. Therefore, the endoscopic follow-up regimen may be attenuated in this group of patients.
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. ttodenhoefer@prostatecentre.com.|Vancouver Prostate Centre, University of British Columbia, 2660 Oak Street, Vancouver, BC, V3Z6H, Canada. ttodenhoefer@prostatecentre.com.
authors.forename: Tilman
authors.initials: T
authors.lastname: Todenhöfer
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. joerg.hennenlotter@med.uni-tuebingen.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Hennenlotter
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. philipp.guttenberg@yahoo.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Guttenberg
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. sarah_mohrhardt@web.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mohrhardt
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. ursula.kuehs@med.uni-tuebingen.de.
authors.forename: Ursula
authors.initials: U
authors.lastname: Kuehs
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. micesser@yahoo.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Esser
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. stefan.aufderklamm@med.uni-tuebingen.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Aufderklamm
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. simone.bier@med.uni-tuebingen.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Bier
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. niklas.harland@med.uni-tuebingen.de.
authors.forename: Niklas
authors.initials: N
authors.lastname: Harland
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. steffen.rausch@med.uni-tuebingen.de.
authors.forename: Steffen
authors.initials: S
authors.lastname: Rausch
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. georgios.gakis@med.uni-tuebingen.de.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. urologie@med.uni-tuebingen.de.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, Eberhard-Karls-University, Hoppe-Seyler-Str. 3, Tübingen, 72076, Germany. christian.schwentner@med.uni-tuebingen.de.
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*; D003558:Cystoscopy / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D011379:Prognosis; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000601:surgery / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor