Is the efficacy of intravescical chemotherapy influenced by cigarette smoking? Data obtained in intermediate risk non muscle invasive bladder carcinoma.

Aim of the study To study recurrence-free rate (RFR) and recurrence-free survival (RFS) according to the smoking status in patients affected by non-muscle invasive carcinoma of the bladder (NMI-BC) treated by intravesical chemotherapy. Materials and methods Smoking status was recorded at study entry. Intravesical epirubicin was administered within 6 hours from TUR at the dose of 80 mg diluted in 50 ml of saline solution. Further adjuvant treatment in low-risk and high-risk patients was given according to physicians’ choice. The remaining patients, at intermediate risk for recurrence, were randomized between two different schemes of intravesical chemotherapy: 5 more weekly instillations (total of 6 instillations) versus 5 more weekly instillations followed by monthly instillations for 10 months (total of 16 instillations). In the case of tumour recurrence within the first year early intravesical epirubicin was repeated. The treatment was continued monthly to complete one year in patients entered in maintenance arm. All patients were submitted to cytology and cystoscopy 3-monthly for 2 years and then 6-monthly for 3 more years. Multivariate statistical analysis was conducted to study the recurrence risk and the response to intravesical chemotherapy in terms of recurrence-free rate (RFR) and recurrence-free survival (RFS) in relation to smoking status at diagnosis. The two different regimens of intravesical chemotherapy were compared in intermediate risk patients. Results Out of 577 consecutive patients, 241 (42%), 188 (33%) and 148 (25%) were current, former and never smokers, respectively. The mean number of cigarettes per day was 20 for a median period of 30 years. Recurrent tumors were statistically more frequent in smokers that in never smokers. The percentage increased from 20% to 42% (p<0.0001), between smokers for less or more than 30 years respectively. No statistically significant difference between current and former smokers emerged in terms of RFR and median time to first recurrence, 71.9% and 65.4% (p=0.23) and 15.9 and 11.7 months (p=0.17) respectively. The 3-year RFS in current and former smokers was 68.9% and 57.0% (p=0.06), respectively. These data did not change in former smokers with increasing time since quitting up to 30 years. The RFS significantly differed between former and never smokers (p=0.019; HR 1.79, C.I. 1.098-2.950). The 3-year RFS was 57.0% and 71.3% respectively. No difference in RFS was evident between the two schedules of intravesical chemotherapy in never smokers (p=0.78) and former smokers (p=0.47). Moreover, this data remained unchanged increasing the time since quitting up to 30 years. Only in current smokers, although no difference emerged in terms of RFS (p=0.27), an advantage of maintenance was evident in terms of RFR (p=0.04) during the treatment period (12 months), disappearing thereafter. Conclusions Recurrent tumors were more frequent in patients smoking for a long period, independently from the number of cigarettes and from smoking cessation. Former smokers remain at high risk for recurrence up to 30 years since quitting. In patients affected by intermediate risk tumors maintenance regimen after 6-weeks induction intravesical chemotherapy is of benefit only in patients continuing to smoke after diagnosis.