Smoking behavior and the risks of tumor recurrence and progression in patients with non-muscle-invasive bladder cancer

Studies on the relationship of cigarette smoking with the risks of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) are inconsistent and prospective data are scarce. Therefore, we aimed to assess the association of smoking behavior with risks of NMIBC recurrence and progression. We used data of the prospective multi-center cohort study UroLife, including 1495 patients with NMIBC who reported information on smoking at 6 weeks post-diagnosis (baseline; reflecting present and pre-diagnosis). This included smoking status (also based on reporting 3 months post-diagnosis), intensity, duration, pack years, and time since smoking cessation, if applicable. Hazard ratios and 95% confidence intervals (CIs) for risks of first recurrence, multiple recurrences, and progression were computed using multivariable proportional hazards regression models. During a total median follow-up period of 4.6 years, 517 patients developed ≥1 recurrence and 163 had progression. Higher versus lowest categories of smoking intensities and pack years up to baseline were significantly associated with a higher risk of first recurrence. No significant linear associations were found, except for smoking intensity among BCG-treated patients (per 10 cigarettes/day increase: HR 1.23, 95%CI 1.02, 1.48). No associations for smoking status, duration, and time since cessation were observed. Analyses of multiple recurrence risk showed comparable results. Regarding progression risk, no consistent associations were found. In conclusion, heavier smoking was associated with higher recurrence risk, particularly among BCG-treated patients. This may be attributable to persistent damage through its carcinogenic compounds. Given the mixed results across different exposures, the effect of smoking behavior on NMIBC prognosis remains unclear.