title: Molecular markers for urothelial bladder cancer prognosis: toward implementation in clinical practice.
abstract: OBJECTIVE
  To summarize the current status of clinicopathological and molecular markers for the prediction of recurrence or progression or both in non-muscle-invasive and survival in muscle-invasive urothelial bladder cancer, to address the reproducibility of pathology and molecular markers, and to provide directions toward implementation of molecular markers in future clinical decision making.
  
  
  METHODS
  Immunohistochemistry, gene signatures, and FGFR3-based molecular grading were used as molecular examples focussing on prognostics and issues related to robustness of pathological and molecular assays.
  
  
  RESULTS
  The role of molecular markers to predict recurrence is limited, as clinical variables are currently more important. The prediction of progression and survival using molecular markers holds considerable promise. Despite a plethora of prognostic (clinical and molecular) marker studies, reproducibility of pathology and molecular assays has been understudied, and lack of reproducibility is probably the main reason that individual prediction of disease outcome is currently not reliable.
  
  
  CONCLUSIONS
  Molecular markers are promising to predict progression and survival, but not recurrence. However, none of these are used in the daily clinical routine because of reproducibility issues. Future studies should focus on reproducibility of marker assessment and consistency of study results by incorporating scoring systems to reduce heterogeneity of reporting. This may ultimately lead to incorporation of molecular markers in clinical practice.
authors.affiliation: Division of Urology, Department of Surgical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands. Electronic address: basvanrhijn@hotmail.com.
authors.forename: Bas W G
authors.initials: BW
authors.lastname: van Rhijn
authors.affiliation: Institute for Cancer Studies and Academic Urology Unit, University of Sheffield, Sheffield, United Kingdom.
authors.forename: James W
authors.initials: JW
authors.lastname: Catto
authors.affiliation: Department of Urology, University Clinic of Erlangen, Erlangen, Germany.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goebell
authors.affiliation: Institute of Pathology, RWTH Aachen University, Aachen, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Knüchel
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Division of Urology, Department of Surgical Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: Henk G
authors.initials: HG
authors.lastname: van der Poel
authors.affiliation: CIC bioGUNE, Bizkaia Technology Park, Derio, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Sanchez-Carbayo
authors.affiliation: Department of Urology, University of Berne, Inselspital, Berne, Switzerland.
authors.forename: George N
authors.initials: GN
authors.lastname: Thalmann
authors.affiliation: Department of Urology, Schön-Klinik, Nürnberg/Fürth, Germany.
authors.forename: Bernd J
authors.initials: BJ
authors.lastname: Schmitz-Dräger
authors.affiliation: Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands; Department of Urology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
mesh_terms: D015415:Biomarkers / Q000032:analysis*; D006801:Humans; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D015415:Biomarkers
keywords: Bladder; Cancer; Marker; Molecular; Reproducibility; Urothelial