Impact of smoking and smoking cessation on outcomes in bladder cancer patients treated with radical cystectomy

Background: Cigarette smoking is the best-established risk factor for urothelial carcinoma development. Objective: To elucidate the association of pretreatment smoking status, cumulative exposure, and time since smoking cessation on outcomes of patients with urothelial carcinoma of the bladder (UCB) treated with radical cystectomy (RC). Design, setting, and participants: We retrospectively collected clinicopathologic and smoking variables, including smoking status, number of cigarettes per day (CPD), duration in years, and time since smoking cessation, for 1506 patients treated with RC for UCB. Lifetime cumulative smoking exposure was categorized as light short-term (≤20 CPD for ≤20 yr), light long-term (≤20 CPD for >20 yr), heavy short-term (>20 CPD for ≤20 yr), and heavy long-term (>20 CPD for >20 yr). Intervention: RC and bilateral lymph node (LN) dissection without neoadjuvant chemotherapy. Outcome measurements and statistical analysis: Logistic regression and competing risk analyses assessed the association of smoking with disease recurrence, cancer-specific mortality, and overall mortality. Results and limitations: There was no difference in clinicopathologic factors between patients who had never smoked (20%), former smokers (46%), and current smokers (34%). Smoking status was associated with the cumulative incidence of disease recurrence (p = 0.004) and cancer-specific mortality (p = 0.016) in univariable analyses and with disease recurrence in multivariable analysis (p = 0.02); current smokers had the highest cumulative incidences. Among ever smokers, cumulative smoking exposure was associated with advanced tumor stages (p < 0.001), LN metastasis (p = 0.002), disease recurrence (p < 0.001), cancer-specific mortality (p = 0.001), and overall mortality (p = 0.037) in multivariable analyses that adjusted for standard characteristics; heavy long-term smokers had the worst outcomes, followed by light long-term, heavy short-term, and light short-term smokers. Smoking cessation ≥10 yr mitigated the risk of disease recurrence (hazard ratio [HR]: 0.44; p < 0.001), cancer-specific mortality (HR: 0.42; p < 0.001), and overall mortality (HR: 0.69; p = 0.012) in multivariable analyses. The study is limited by its retrospective nature. Conclusions: Smoking is associated with worse prognosis after RC for UCB. This association seems to be dose-dependent, and its effects are mitigated by >10 yr smoking cessation. Health care practitioners should counsel smokers regarding the detrimental effects of smoking and the benefits of smoking cessation on UCB etiology and prognosis.