Urinary Cotinine: A Promising Marker of Recurrence of Non-muscle Invasive Bladder Tumor

Main Article Content

Maher Abdsessater Johnny Boustany Anthony Kanbar Antoine Kassis Charbel El Hachem Rodrigue Saad Charbel Dabal Sabine Boueiri Serge Assaf Joey El Khoury Rami Halabi Raghid El Khoury

Abstract

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.

Keywords: Bladder Cancer, Non-muscle invasive bladder cancer, Urinary Cotinine, Smoking, Tobacco, Tobacco smoke exposure, Recurrence, biomarker

Article Details

How to Cite
ABDSESSATER, Maher et al. Urinary Cotinine: A Promising Marker of Recurrence of Non-muscle Invasive Bladder Tumor. Medical Research Archives, [S.l.], v. 11, n. 12, jan. 2024. ISSN 2375-1924. Available at: <https://esmed.org/MRA/mra/article/view/4779>. Date accessed: 26 dec. 2024. doi: https://doi.org/10.18103/mra.v11i12.4779.
Section
Research Articles

References

1 R. L. Siegel, K. D. Miller, and A. Jemal, “Cancer Statistics, 2017.,” CA. Cancer J. Clin., vol. 67, no. 1, pp. 7–30, Jan. 2017, doi: 10.3322/caac.21387.
2 M. Babjuk et al., “EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013.,” Eur. Urol., vol. 64, no. 4, pp. 639–653, Oct. 2013, doi: 10.1016/j.eururo.2013.06.003.
3 R. J. Sylvester et al., “Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials.,” Eur. Urol., vol. 49, no. 3, pp. 466–467, Mar. 2006, doi: 10.1016/j.eururo.2005.12.031.
4 M. Miyake, K. Fujimoto, and Y. Hirao, “Active surveillance for nonmuscle invasive bladder cancer,” Investig. Clin. Urol., vol. 57 Suppl 1, no. Suppl 1, pp. S4–S13, Jun. 2016, doi: 10.4111/icu.2016.57.S1.S4.
5 S. S. Chang et al., “Diagnosis and Treatment of Non-Muscle Invasive Bladder Cancer: AUA/SUO Guideline.,” J. Urol., vol. 196, no. 4, pp. 1021–1029, Oct. 2016, doi: 10.1016/j.juro.2016.06.049.
6 F. A. Yafi, F. Brimo, J. Steinberg, A. G. Aprikian, S. Tanguay, and W. Kassouf, “Prospective analysis of sensitivity and specificity of urinary cytology and other urinary biomarkers for bladder cancer.,” Urol. Oncol., vol. 33, no. 2, pp. 66.e25–31, Feb. 2015, doi: 10.1016/j.urolonc.2014.06.008.
7 J. J. Fantony and B. A. Inman, “It May Be Time to Abandon Urine Tests for Bladder Cancer.,” J. Natl. Compr. Canc. Netw., vol. 13, no. 9, pp. 1163–1166, Sep. 2015, doi: 10.6004/jnccn.2015.0141.
8 Q. Liang, G. Zhang, W. Li, J. Wang, and S. Sheng, “Comparison of the diagnostic performance of fluorescence in situ hybridization (FISH), nuclear matrix protein 22 (NMP22), and their combination model in bladder carcinoma detection: a systematic review and meta-analysis,” Onco. Targets. Ther., vol. 12, pp. 349–358, Dec. 2018, doi: 10.2147/OTT.S186065.
9 J. Fernandez-Gomez et al., “Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guérin: multivariate analysis of data from four randomized CUETO trials.,” Eur. Urol., vol. 53, no. 5, pp. 992–1001, May 2008, doi: 10.1016/j.eururo.2007.10.006.
10 How Tobacco Smoke Causes Disease: The Biology and Behavioral Basis for Smoking-Attributable Disease: A Report of the Surgeon General. Atlanta (GA), 2010.
11 J. P. Gray and G. J. Hall, “Cotinine,” P. B. T.-E. of T. (Third E. Wexler, Ed. Oxford: Academic Press, 2014, pp. 1050–1051.
12 J. E. Henningfield and R. M. Keenan, “Nicotine delivery kinetics and abuse liability.,” J. Consult. Clin. Psychol., vol. 61, no. 5, pp. 743–750, 1993, doi: 10.1037/0022-006X.61.5.743.
13 F. de Waard, J. M. Kemmeren, L. A. van Ginkel, and A. A. Stolker, “Urinary cotinine and lung cancer risk in a female cohort,” Br. J. Cancer, vol. 72, no. 3, pp. 784–787, Sep. 1995, doi: 10.1038/bjc.1995.411.
14 D. Behera, R. Uppal, and S. Majumdar, “Urinary levels of nicotine & cotinine in tobacco users.,” Indian J. Med. Res., vol. 118, pp. 129–133, Sep. 2003.
15 H.-S. Jung et al., “Can urinary cotinine predict nicotine dependence level in smokers?,” Asian Pac. J. Cancer Prev., vol. 13, no. 11, pp. 5483–5488, 2012, doi: 10.7314/apjcp.2012.13.11.5483.
16 Cheng, S., Ko, D., Kim, H. S., & Lee, Y. (2015). Urinary Cotinine Concentration and Nicotine Dependence. Nicotine & Tobacco Research, 17(1), 99–105. https://doi.org/10.1093/ntr/ntu123
17 Hsu, H.-H., Tzeng, H.-E., Ho, C.-L., Wang, L.-J., Yeh, B.-W., Wu, W.-J., & Li, W.-M. (2017). Risk factors for the recurrence of bladder urothelial tumors in high-risk patients after transurethral resection. PLOS ONE, 12(8), e0182883. https://doi.org/10.1371/journal.pone.0182883
18 Rink, M., Fajkovic, H., Cha, E. K., Gupta, A., Karakiewicz, P. I., Chun, F. K., ... Shariat, S. F. (2012). Death certificates are valid for the determination of cause of death in patients with upper and lower tract urothelial carcinoma. European Urology, 61(4), 854–855. https://doi.org/10.1016/j.eururo.2012.01.024