Sex differences in bladder cancer outcomes among smokers with advanced bladder cancer
Authors: Boström Peter J. , Alkhateeb Sultan , Trottier Greg , Athanasopoulos Paul Z. , Mirtti Tuomas , Kortekangas Hannes , Laato Matti , van Rhijn Bas , van der Kwast Theo , Fleshner Neil E. , Jewett Michael A. , Finelli Antonio , Zlotta Alexandre R. 
Published: August 2011

Study Type – Aetiology (individual cohort)Level of Evidence 2bWhat's known on the subject? and What does the study add?Smoking is well described among the most important risk factors for bladder cancer. It is also known that higher quantity of tobacco exposure is associated with higher bladder cancer risk and that smoking cessation is known to be associated with lower risk of bladder cancer. Furthermore, among patients with non‐muscle invasive bladder cancer, smoking cessation decreases the risk of tumour recurrence. On the other hand, the effect of smoking on tumour stages at presentation and especially on prognosis is not well studied.The current study describes the presentation and outcome of 564 patients (64% smokers, 36% non‐smokers) treated with radical cystectomy. Patients with smoking history have more advanced outcome at the time of radical surgery and significantly worse outcome after surgery when compared to non‐smokers, although the effect of smoking was not significant when survival was studied in multivariable analysis including classic prognostic parameters such as tumour grade, stage and adjuvant chemotherapy. Finally, there was a surprising finding that history of smoking affected outcome among male patients but such effect was not noted among female patients.OBJECTIVE• To study the effect of smoking on bladder cancer presentation and outcome in a large cystectomy population.PATIENTS AND METHODS• A database including 546 patients from the University Health Network (Toronto, Canada) and Turku University Hospital (Turku, Finland) was studied.• In addition to the association of smoking with clinicopathological parameters, the effect of smoking on survival was analyzed.• Categorical data were analyzed by the chi‐squared test and numerical data were analyzed by Student's t‐test.• The Kaplan–Meier method, log‐rank test and a proportional hazards model were used to estimate the effect of smoking on survival.RESULTS• In total, 352 patients (64%) were smokers and 194 (36%) were non‐smokers.• Smokers had more frequently advanced tumours and nodal metastasis.• The 10‐year disease‐specific survival (DSS) was 52% vs 66% for smokers and non‐smokers, respectively (P= 0.039).• Smokers also had significantly worse overall survival (10‐year overall survival 37% vs 62%; P= 0.015).• Smoking affected significant DSS among men (P= 0.012), although no effect was observed among women.• In a univariate model smoking was associated with a hazard ratio (HR) of 1.4 (95% confidence interval, CI, 1.0–1.9) for bladder cancer specific mortality and 1.4 (95% CI, 1.1–1.8) for overall mortality.• In a multivariate model, smoking did not impact on DSS (HR, 1.1; 95% CI, 0.8–1.6; P= 0.41).• In addition to advanced stage and nodal metastasis, female sex was an independent risk factor for DSS (HR, 1.6; 95% CI, 1.1–2.3; P= 0.007).CONCLUSIONS• Smokers appear to have worse outcomes after radical cystectomy for bladder cancer; however, it does not appear to be an independent prognostic factor for survival.• Smoking affected survival only among men.• Women had poorer survival but smoking was not a contributing factor to this.