Urinary cotinine, measure of tobacco exposure, associated with bladder cancer recurrence
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High urinary levels of cotinine appeared associated with a fourfold increased risk for recurrence of nonmuscle invasive bladder cancer in smokers, according to a study presented during the virtual European Association of Urology Congress.
“In this study, we highlighted the importance of urinary cotinine level in the surveillance of [nonmuscle invasive bladder cancer (NMIBC)] and suggested it as a promising, accessible, noninvasive, low-cost biomarker that can change the management of bladder cancer by reducing the frequency of cystoscopies,” Maher Abdessater, MD, MPH, urologist at Notre Dame des Secours University Hospital in Lebanon, told Healio.
Although smoking is a leading risk factor for bladder cancer, not much is known of whether recurrence rates are related to nicotine metabolites in urine, according to researchers. Because cotinine is considered the best marker of tobacco exposure among all nicotine metabolites, Abdessater and colleagues aimed to evaluate the relationship of urinary cotinine level and recurrence of NMIBC.
“The field of biomarkers for bladder tumor detection and surveillance improves rapidly,” Abdessater said. “To date, no bladder tumor biomarker has proved its superiority to classic urine cytology and cystoscopy. The first motivation was to try to find a noninvasive, less expensive way to perform surveillance of NMIBC.”
The study included 135 patients (mean age, 64 years; range, 36-78; 100% white; median duration of smoking, 30.3 years) who had similar profile of exposure to carcinogens related to bladder cancer and had already been diagnosed with NMIBC treated by resection only, with no other condition that could distort results, such as urinary infections. Patients attended Notre Dame de Secours University Hospital between January 2018 and June 2019 for follow-up cystoscopies.
Researchers measured cotinine levels from a sample of voided urine before cystoscopy. They divided patients into two groups, depending on the level of cotinine in their urine: moderate smokers (less than 550 ng/mL, n = 80) and heavy smokers (more than 550 ng/mL, n = 55). Researchers noted that some patients who identified as nonsmokers or moderate smokers had cotinine levels consistent with heavy smoking.
The investigators assessed the relationship between variables with a Fisher exact test.
Results showed recurrence of NMIBC in 75% of the heavy-smoker group and in 18.1% of the moderate-smoker group. Researchers reported an association of cotinine levels higher than 550ng/mL with a higher risk for bladder cancer, with a relative risk of 4.16 (P = .025).
“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,” Abdessater said in a press release. “Although our sample size is small, the results to date show that cotinine could be a potential biomarker for recurrence of bladder cancer and is worth further investigation.”
As the study continues, investigators are looking for other institutions that may be interested in collaborating in order to bring the research to a wider range of patients and health care systems.
“Confirming this promising result by larger-scale studies with bigger sample sizes and longer follow-up periods is primordial and necessary before establishing the need for routine urinary cotinine level testing in clinical practice,” Abdessater told Healio.
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Peter Wiklund, MD, PhD
This is an interesting study showing an association between concentration of nicotine metabolites (cotinine) in urine and risk for recurrence of nonmuscle-invasive bladder cancer.
However, it is a small study with 135 patients and confirmation in a larger patient group is needed. It is not clear from the study how the results are affected by the amount of smoking and if nonsmokers will have the same findings.
One interpretation of the results may be that heavy smokers have higher levels of nicotine metabolites in the urine and that, in fact, the number of cigarettes increases the risk for tumor recurrence.
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Abdesatter M, et al. Abstract P0726. Presented at: European Association of Urology Congress (virtual meeting); July 8-12, 2021.
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