title: Inflammatory biomarkers and bladder cancer prognosis: a systematic review.
abstract: BACKGROUND
  Host immune response has an impact on tumour development and progression. There is interest in the use of inflammatory biomarkers (InfBMs) in cancer care. Although several studies assessing the potential prognostic value of InfBMs in cancer have been published in the past decades, they have had no impact on the management of patients with urothelial bladder carcinoma (UBC).
  
  
  OBJECTIVE
  To review and summarise the scientific literature on the prognostic value of tumour, serum, urine, and germline DNA InfBMs on UBC.
  
  
  METHODS
  A systematic review of the literature was performed searching the Medline and Embase databases for original articles published between January 1975 and November 2013. The main inclusion criterion was the provision of a survival analysis (Kaplan-Meier and/or Cox) according to the Reporting Recommendations for Tumor Marker Prognostic Studies guidelines for the assessment of prognostic markers. We focused on markers assessed at least twice in the literature. Findings are reported following Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines.
  
  
  RESULTS
  Overall, 34 publications, mostly retrospective, fulfilled the main inclusion criterion. Main limitations of these studies were missing relevant information about design or analysis and heterogeneous methodology used. Inflammatory cells, costimulatory molecules in tumour cells, and serum cytokines showed prognostic significance, mainly in univariable analyses. High C-reactive protein values were consistently reported as an independent prognostic factor for mortality in invasive UBC.
  
  
  CONCLUSIONS
  There is a dearth of studies on InfBMs in UBC compared with other tumour types. Evidence suggests that InfBMs may have an impact on the management of patients with UBC. Currently, methodological drawbacks of the studies limit the translational potential of results.
  
  
  RESULTS
  In this review, we analysed studies evaluating the impact of inflammatory response on bladder cancer progression. Despite methodological limitations, some inflammatory biomarkers should be further analysed because they hold promise to improve patient care.
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Urology Department, Henri Mondor Academic Hospital, INSERM U955Eq7, Créteil, France.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Masson-Lecomte
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Rava
authors.affiliation: Epithelial Carcinogenesis Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.affiliation: Department of Pathology, University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain; Pathology Department, Henri Mondor Academic Hospital, INSERM U955Eq7, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Allory
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. Electronic address: nmalats@cnio.es.
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
mesh_terms: D015703:Antigens, CD / Q000032:analysis; D060890:B7-H1 Antigen / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood* / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes; D002277:Carcinoma / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000401:mortality; D051858:Forkhead Transcription Factors / Q000032:analysis; D005819:Genetic Markers; D006801:Humans; D007249:Inflammation / Q000097:blood*; D018836:Inflammation Mediators / Q000097:blood*; D015850:Interleukin-6 / Q000235:genetics; D018655:Lymphocyte Count; D009504:Neutrophils; D011379:Prognosis; D059016:Tumor Microenvironment / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000097:blood* / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000401:mortality
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D018836:Inflammation Mediators; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Biomarkers; Bladder cancer; Inflammation; Progression; Survival