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Introduction and objectives: Nicotine is well known to be an addictive compound of tobacco, but it is not primarily carcinogenic. It is metabolized to cotinine, which is considered the best marker of tobacco exposure. Little is known whether recurrence rate of bladder cancer is related to nicotine metabolites eliminated in urine. We aim by this study to evaluate the relation between urinary cotinine level and the recurrence of bladder cancer.

Materials and Methods: Between January 2018 and June 2022, a cross sectional study was conducted. Enrolled patients were smokers already diagnosed with non-muscle invasive bladder cancer, treated by resection only, and presenting for a follow up cystoscopy. Included patients had unchanged smoking habits in the day before the procedure, same ethnicity (Caucasians) and no additional professional exposure. Cotinine level was measured on a sample of voided urine before cystoscopy. Tumor recurrence was considered positive independently from the histological type, and was assessed by direct vision cystoscopy. Patients were considered moderate or heavy smokers depending on the level of cotinine in their urine samples (< or > 550 ng/ml respectively). A Fisher Exact Test was used to assess the relationship between variables.

Results: A total of 135 patients was included. Mean age was 64 years (range 36 to 78). The mean duration of smoking was 30.3 years. Urinary cotinine level was > 550 ng/ml in 80 patients (59.26%) and < 550 ng/ml in 55 patients (40.74%). Recurrence was identified in 70 patients (51.85%) and was absent in the remaining 65 (48.15%). Recurrence was observed in 68.75% of the heavy smokers and in 27.27 % of moderate smokers. Cotinine level higher than 550 ng/mL was linked to an increased risk of bladder cancer, with a relative risk of 4.16 (p-value < 0,025).

Conclusion: High urinary cotinine levels (>550 ng/ml) conveys a 4 folds’ risk for the recurrence of bladder cancer in smokers. Additional prospective studies are needed to better understand the relation between urinary cotinine levels and bladder cancer, and its usefulness in bladder cancer surveillance.