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Nicotine metabolite linked to NMIBC recurrence


Investigators have reported an association between high urinary cotinine (UC) levels and non–muscle invasive bladder cancer (NMIBC) recurrence in smokers, with a 4-fold greater risk of recurrence in patients with high levels of the nicotine metabolite.

The research was presented at the 2021 European Association of Urology Annual Congress by Maher Abdessater, MD, MPH, of Notre Dame de Secours University Hospital in Lebanon.1

“[Cotinine is] the best marker for tobacco exposure, but little is known about its carcinogenic effect. Additionally, little is known whether the recurrence of bladder cancer can be related to the nicotine metabolites eliminated in urine,” Abdessater explained. To this end, the investigators sought to evaluate the association between UC level and NMIBC recurrence.

The investigators performed a cross sectional study between January 2018 and June 2019. The study enrolled patients who were smokers, received a diagnosis of NMIBC that was treated with resection only, and who were presenting for a follow-up cystoscopy. Cotinine was measured on a sample of voided urine prior to cystoscopy. Patients with a UC level less than 550 ng/mL were considered moderate smokers, whereas patients with a UC level greater than 550 ng/mL were considered heavy smokers. Tumor recurrence was evaluated via cystoscopy. A Fisher Exact Test was used for statistical analysis.

The cohort included 135 patients aged 36 to 78 years (mean age, 64). All patients were Caucasian and had a similar profile of exposure to carcinogens related to bladder cancer. Eighty-two percent of patients were male, and 12% were female.

The investigators found that 40.74% of the cohort were moderate smokers and 59.26% were heavy smokers. Overall tumor recurrence rate was 51.85%.

“Specifically, tumor recurrence was observed in 75% of heavy smokers and 18% of moderate smokers. This result was statistically significant,” Abdessater said, with a relative risk of 4.16 (P <.025) reported.

In a news release about the results, Abdessater discussed the ease of use and low cost of using cotinine levels to detect bladder cancer recurrence.2

“One of the major advantages of using cotinine is that it can be detected using a simple urine test, which is a cheaper and less invasive alternative to cystoscopy. It can also pick up where patients are not accurately reporting their smoking levels, or where passive smoking combined with active smoking is pushing them into the heavy smoker category."

“Additional prospective studies are needed to better understand the relation between urinary cotinine levels and bladder cancer and to evaluate its usefulness in bladder cancer surveillance,” Abdessater said in his concluding remarks.

Although the data reported by the investigators were from the period between January 2018 and June 2019, the study is ongoing, and the investigators are seeking additional institutions to collaborate on the effort, according to the news release.

Commenting on the results in the news release, EAU Secretary-General Adjunct Professor Arnulf Stenzl said, “This study definitely gives food for thought, although as yet the findings are only in a small number of patients. We now need to test this in a larger trial, and also look at more precise indications of smoking levels and the type of cigarettes involved—particularly whether they are filtered or not. It would be interesting as well to look at whether cotinine levels are higher in patients with other risk factors for bladder cancer, such as exposure to arsenic or industrial benzole."


1. Abdessater M, Kanbar A, El Khoury J, et al. Role of urinary cotinine level in the recurrence of non-muscle invasive bladder cancer. Paper presented at: 2021 European Association of Urology Annual Congress. July 8-12; virtual. Abstract P0726

2. Nicotine by-product can predict recurrence of cancer. News release. European Association of Urology. July 8, 2021. Accessed July 12, 2021. https://www.eurekalert.org/pub_releases/2021-07/eaou-nbc070721.php

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