MP56-07: Impact of Smoking, Cumulative Exposure and Cessation on Oncologic Outcomes after Radical Cystectomy and Adjuvant Chemotherapy for locally-advanced Bladder Cancer: A Multicenter Study
Introduction: Next to bladder carcinogenesis, smoking is also highly associated with more aggressive disease. Moreover, it can deteriorate pharmacokinetics and reduces response to neoadjuvant chemotherapy upfront radical cystectomy(RC). Knowledge of its impact on the efficacy of chemotherapy in the adjuvant setting is, however, still limited. This was the first study to investigate the effects of smoking habits on oncologic outcomes after RC and adjuvant chemotherapy(AC) for locally-advanced bladder cancer(BC). Methods: This multicenter study included patients from Europe and the US treated with RC and AC between 1995 and 2018. Clinicopathological factors, chemo regimes and smoking data including cumulative exposure (quantity + duration) and time since cessation were collected. Ever smokers were categorized into groups according to their lifetime cumulative exposure. Kaplan-Meier curves and log-rank tests were used to compare survival outcomes; uni- and multivariable Cox regression analyses to assess the association of smoking with recurrence-free survival(RFS), cancer-specific survival(CSS) and overall survival(OS). Results: 448 patients were included. Among them, 96(21%) were never, 204(46%) former and 147(33%) current smokers. AC with Cisplatin-based regimes(Cis mono, Cis/Gem, MVAC) were used in over 90% of cases; 10% received Carbo/Gem or others. There were no differences in clinicopath. characteristics across the groups. Current smokers were at a significantly higher risk of disease recurrence compared to never smokers(p=0.02). However, never, former and current smokers had comparable 3 year-estimates of OS, CSS and RFS. The cumulative smoking exposure was associated with all oncological endpoints(all p<0.04) and long-term smokers (>20years), both light and heavy, had the worst outcomes(all p<0.03). On uni- and multivariable regression analyses, long-term smoking was a predictor for worse OS, CSS and RFS; smoking cessation for >10years was associated with lower risks for disease recurrence and cancer-specific death(p < 0.042). Conclusions: Smoking may reduce the efficacy of chemotherapy for BC and is an independent predictor for disease recurrence after RC and AC. Duration, rather than intensity, seems to be a key determinant of oncologic outcomes. Smoking cessation for >10years may mitigate the risks for disease recurrence and cancer-specific mortality. Smoking cessation should be integrated into urologic counselling regardless of the disease state. SOURCE OF Funding: None.
