Impact of smoking status and cumulative exposure on intravesical recurrence of upper tract urothelial carcinoma after radical nephroureterectomy

Objective To assess the impact of cigarette smoking status, cumulative smoking exposure, and time from cessation on intravesical recurrence (IVR) outcomes in patients treated with radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). Patients and Methods In all, 519 patients underwent RNU at five institutions. Smoking history included smoking status, quantity of cigarettes smoked per day (cpd), duration, and time from cessation. The cumulative smoking exposure was categorised as light-short-term (≤19 cpd and ≤19.9 years), moderate (all combinations except light-short-term and heavy-long-term), and heavy-long-term (≥20 cpd and ≥20 years). Univariable/multivariable cox regression analyses assessed the effects of smoking on IVR. Results In all, 190 patients (36%) never smoked; 205 (40%) and 125 (24%) were former and current smokers, respectively. Among smokers, 42 (8%), 185 (36%), and 102 (20%) patients were light-short-term, moderate, and heavy-long-term smokers, respectively. Within a median follow-up of 37 months, 152 patients (29%) had IVR. Actuarial IVR-free-survival estimates (standard error) at 2, 5, and 10 years were 72 (2)%, 58 (3)%, and 51 (4)%, respectively. In multivariable analyses, current smoking status, smoking intensity (≥20 cpd), smoking duration (≥20 years), and heavy-long-term smoking were associated with higher risk of IVR (all P ≤ 0.01). Patients who quit smoking ≥10 years before RNU had better IVR outcomes than current smokers and those patients who quit smoking <10 years before RNU. Conclusions Cigarette smoking is significantly associated with IVR in patients treated with RNU for UTUC. Current and heavy-long-term smokers have the highest risk of IVR. Smoking cessation for >10 years before RNU seems to mitigate these detrimental effects.