title: Significant Role of Lifetime Cigarette Smoking in Worsening Bladder Cancer and Upper Tract Urothelial Carcinoma Prognosis: A Meta-Analysis.
abstract: OBJECTIVE
  Although cigarette smoking is a well established risk factor for urothelial cancer, its role in urothelial cancer prognosis is still undetermined. In this meta-analysis we quantify the role of lifetime smoking history in bladder cancer recurrence, progression and survival by pooling available data on nonmuscle invasive bladder cancer, muscle invasive bladder cancer and upper tract urothelial carcinoma.
  
  
  METHODS
  A total of 24 studies, comprising data from 13,114 patients with bladder cancer and 2,259 patients with upper tract urothelial carcinoma, were included in this meta-analysis. Publication bias was addressed through Egger's test, and the heterogeneity among studies was assessed by the I(2) test statistic and subgroup analyses.
  
  
  RESULTS
  Current smokers at diagnosis are at increased risk for local recurrence in nonmuscle invasive bladder cancer (HR 1.27, 95% CI 1.09-1.46) and smokers with muscle invasive bladder cancer have an increased risk of dying of bladder cancer (HR 1.23, 95% CI 1.02-1.44). In the upper tract urothelial carcinoma population smokers have an increased risk of recurrence in the operative bed (HR 1.57, 95% CI 1.19-1.95) and of death from upper tract urothelial carcinoma (HR 1.53, 95% CI 1.13-1.92). We did not identify significant heterogeneity among included studies.
  
  
  CONCLUSIONS
  The body of evidence is limited due to the absence of prospective studies. However, the results from this meta-analysis unambiguously support the hypothesis that lifetime cigarette smokers are at increased risk for a more malignant type of urothelial carcinoma associated with a worse prognosis.
authors.affiliation: Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom. Electronic address: f.vanosch@maastrichtuniversity.nl.
authors.forename: Frits H M
authors.initials: FH
authors.lastname: van Osch
authors.affiliation: Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Sylvia H J
authors.initials: SH
authors.lastname: Jochems
authors.affiliation: Department of Pharmacology and Toxicology, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
authors.forename: Frederik J
authors.initials: FJ
authors.lastname: van Schooten
authors.affiliation: Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Richard T
authors.initials: RT
authors.lastname: Bryan
authors.affiliation: Department of Complex Genetics, NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands; Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, United Kingdom.
authors.forename: Maurice P
authors.initials: MP
authors.lastname: Zeegers
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000209:etiology*; D018450:Disease Progression; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology*; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors; D014516:Ureteral Neoplasms / Q000209:etiology*; D001749:Urinary Bladder Neoplasms / Q000209:etiology*
keywords: carcinoma; meta-analysis; prognosis; smoking; transitional cell; urinary bladder neoplasms