Significant Role of Lifetime Cigarette Smoking in Worsening Bladder Cancer and Upper Tract Urothelial Carcinoma Prognosis: A Meta-Analysis

J Urol. 2016 Apr;195(4 Pt 1):872-9. doi: 10.1016/j.juro.2015.10.139. Epub 2015 Oct 31.


Purpose: 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.

Materials and 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.

Keywords: carcinoma; meta-analysis; prognosis; smoking; transitional cell; urinary bladder neoplasms.

Publication types

  • Meta-Analysis

MeSH terms

  • Carcinoma, Transitional Cell / etiology*
  • Disease Progression
  • Humans
  • Kidney Neoplasms / etiology*
  • Smoking / adverse effects*
  • Time Factors
  • Ureteral Neoplasms / etiology*
  • Urinary Bladder Neoplasms / etiology*