Bladder cancer incidence and mortality among men with and without castration therapy for prostate cancer – a nation-wide cohort study
DOI:
https://doi.org/10.2340/1651-226X.2024.40969Keywords:
Urinary Bladder Cancer, Anti-hormonal Treatment, Androgen receptor, GenderAbstract
Background and purpose: Bladder cancer (BC) is a common malignancy in the Western World with men being diagnosed almost four times as often as women. The etiology of bladder cancer may involve sex hormones. Prostate cancer (PCa) patients treated with chemical castration, such as androgen deprivation therapy, or surgical castration, may therefore have a lower risk of developing bladder cancer.
Patients/material and methods: In a nation-wide population-based cohort study using national Danish registry data, we included a cohort of men with a first-time PCa diagnosis between 2002 and 2018 divided according to antihormonal treatment in the first year after PCa diagnosis and a comparison cohort consisting of 10 age-matched persons for each PCa patient. Each individual was followed from 1 year after PCa diagnosis until death or end of follow-up. We computed cumulative incidences (risk) and hazard ratios (HRs) for BC. In a second cohort analysis, we determined overall survival and BC-specific mortality, determined from date of BC diagnosis until death.
Results and interpretation: We included 48,776 PCa patients of whom 13,592 were treated with chemical castration, 2,261 with surgical castration, and 32,923 received no antihormonal treatment. The 5-year risk of BC for each PCa group was 1.1%, 0.7%, and 1.3%, respectively, corresponding to an adjusted HR of 1.13 (95% CI 0.98; 1.31), 0.95 (95% CI 0.62; 1.47), and 1.18 (95% CI 1.09; 1.28) compared to individuals without PCa. Patients receiving antihormonal treatment had a slightly lower incidence of BC compared to individuals without PCa, however, this was not supported by the HRs. The treatment, however, was not associated with overall survival.
Downloads
References
Strope SA, Montie JE. The causal role of cigarette smoking in bladder cancer initiation and progression, and the role of urologists in smoking cessation. J Urol. 2008;180(1):31–7; discussion 7.
https://doi.org/10.1016/j.juro.2008.03.045 DOI: https://doi.org/10.1016/j.juro.2008.03.045
Halaseh SA, Halaseh S, Alali Y, Ashour ME, Alharayzah MJ. A review of the etiology and epidemiology of bladder cancer: all you need to know. Cureus. 2022;14(7):e27330.
https://doi.org/10.7759/cureus.27330 DOI: https://doi.org/10.7759/cureus.27330
Rai BP, Luis Dominguez Escrig J, Vale L, Kuusk T, Capoun O, Soukup V, et al. Systematic review of the incidence of and risk factors for urothelial cancers and renal cell carcinoma among patients with haematuria. Eur Urol. 2022;82(2):182–92.
https://doi.org/10.1016/j.eururo.2022.03.027 DOI: https://doi.org/10.1016/j.eururo.2022.03.027
Hartge P, Harvey EB, Linehan WM, Silverman DT, Sullivan JW, Hoover RN, et al. Unexplained excess risk of bladder cancer in men. J Natl Cancer Inst. 1990;82(20):1636–40.
https://doi.org/10.1093/jnci/82.20.1636 DOI: https://doi.org/10.1093/jnci/82.20.1636
Deltourbe L, Lacerda Mariano L, Hreha TN, Hunstad DA, Ingersoll MA. The impact of biological sex on diseases of the urinary tract. Mucosal Immunol. 2022;15(5):857–66.
https://doi.org/10.1038/s41385-022-00549-0 DOI: https://doi.org/10.1038/s41385-022-00549-0
Desai K, McManus JM, Sharifi N. Hormonal therapy for prostate cancer. Endocr Rev. 2021;42(3):354–73.
https://doi.org/10.1210/endrev/bnab002 DOI: https://doi.org/10.1210/endrev/bnab002
DMCG. Danish clinical guideline for treating hormonesensitive prostate cancer. 2022. [Cited April 18th 2024] Available from: https://www.dmcg.dk/kliniske-retningslinjer
Ide H, Miyamoto H. The role of steroid hormone receptors in urothelial tumorigenesis. Cancers. 2020;12(8):2155.
https://doi.org/10.3390/cancers12082155 DOI: https://doi.org/10.3390/cancers12082155
Santella C, Rouette J, Brundage MD, Filion KB, Azoulay L. Androgen deprivation therapy for prostate cancer and the risk of bladder cancer: a systematic review of observational studies. Urol Oncol. 2020;38(11):816–25.
https://doi.org/10.1016/j.urolonc.2020.04.028 DOI: https://doi.org/10.1016/j.urolonc.2020.04.028
Izumi K, Taguri M, Miyamoto H, Hara Y, Kishida T, Chiba K, et al. Androgen deprivation therapy prevents bladder cancer recurrence. Oncotarget. 2014;5(24):12665–74.
https://doi.org/10.18632/oncotarget.2851 DOI: https://doi.org/10.18632/oncotarget.2851
Shiota M, Kiyoshima K, Yokomizo A, Takeuchi A, Kashiwagi E, Dejima T, et al. Suppressed recurrent bladder cancer after androgen suppression with androgen deprivation therapy or 5 alpha-Reductase Inhibitor. J Urol. 2017;197(2):308–13.
https://doi.org/10.1016/j.juro.2016.08.006 DOI: https://doi.org/10.1016/j.juro.2016.08.006
Wu SC, Kwon D, Jue JS, Chen FV, Velasquez Escobar MC, Punnen S, et al. Androgen suppression therapy is associated with lower recurrence of non-muscle-invasive bladder cancer. Eur Urol Focus. 2021;7(1):142-147.
https://doi.org/10.1016/j.euf.2019.04.021 DOI: https://doi.org/10.1016/j.euf.2019.04.021
Shiota M, Yokomizo A, Takeuchi A, Imada K, Kiyoshima K, Inokuchi J, et al. Secondary bladder cancer after anticancer therapy for prostate cancer: reduced comorbidity after androgen-deprivation therapy. Oncotarget. 2015;6(16):14710–9.
https://doi.org/10.18632/oncotarget.3817 DOI: https://doi.org/10.18632/oncotarget.3817
Moschini M, Zaffuto E, Karakiewicz P, Mattei A, Gandaglia G, Fossati N, et al. The effect of androgen deprivation treatment on subsequent risk of bladder cancer diagnosis in male patients treated for prostate cancer. World J Urol. 2019;37(6):1127–35.
https://doi.org/10.1007/s00345-018-2504-3 DOI: https://doi.org/10.1007/s00345-018-2504-3
Wallner LP, Wang R, Jacobsen SJ, Haque R. Androgen deprivation therapy for treatment of localized prostate cancer and risk of second primary malignancies. Cancer Epidemiol Biomarkers Prev. 2013;22(2):313–6.
https://doi.org/10.1158/1055-9965.EPI-12-1137 DOI: https://doi.org/10.1158/1055-9965.EPI-12-1137
Schmidt M, Schmidt SAJ, Adelborg K, Sundbøll J, Laugesen K, Ehrenstein V, et al. The Danish health care system and epidemiological research: from health care contacts to database records. Clin Epidemiol. 2019;11:563–91.
https://doi.org/10.2147/CLEP.S179083 DOI: https://doi.org/10.2147/CLEP.S179083
Schmidt M, Pedersen L, Sørensen HT. The Danish Civil Registration System as a tool in epidemiology. Eur J Epidemiol. 2014;29(8):541–9.
https://doi.org/10.1007/s10654-014-9930-3 DOI: https://doi.org/10.1007/s10654-014-9930-3
Schmidt M, Schmidt SAJ, Sandegaard JL, Ehrenstein V, Pedersen L, Sørensen HT. The Danish National Patient Registry: a review of content, data quality, and research potential. Clin Epidemiol. 2015;7:449-90.
https://doi.org/10.2147/CLEP.S91125 DOI: https://doi.org/10.2147/CLEP.S91125
Kildemoes HW, Sørensen HT, Hallas J. The Danish national prescription registry. Scand J Public Health. 2011;39(7 Suppl):38–41.
https://doi.org/10.1177/1403494810394717 DOI: https://doi.org/10.1177/1403494810394717
Bjerregaard B, Larsen OB. The Danish Pathology Register. Scand J Public Health. 2011;39(7_suppl):72–4.
https://doi.org/10.1177/1403494810393563 DOI: https://doi.org/10.1177/1403494810393563
Helweg-Larsen K. The Danish register of causes of death. Scand J Public Health. 2011;39(7 Suppl):26–9.
https://doi.org/10.1177/1403494811399958 DOI: https://doi.org/10.1177/1403494811399958
R.C.T. R: a language and environment for statistical computing. 2020. Available from: https://www.R-project.org/
Sikic D, Wirtz RM, Wach S, Dyrskjøt L, Erben P, Bolenz C, et al. Androgen receptor mRNA expression in urothelial carcinoma of the bladder: a retrospective analysis of two independent cohorts. Transl Oncol. 2019;12(4):661–8.
https://doi.org/10.1016/j.tranon.2019.01.005 DOI: https://doi.org/10.1016/j.tranon.2019.01.005
Miyamoto H, Yang Z, Chen YT, Ishiguro H, Uemura H, Kubota Y, et al. Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst. 2007;99(7):558–68.
https://doi.org/10.1093/jnci/djk113 DOI: https://doi.org/10.1093/jnci/djk113
Hsu JW, Hsu I, Xu D, Miyamoto H, Liang L, Wu XR, et al. Decreased tumorigenesis and mortality from bladder cancer in mice lacking urothelial androgen receptor. Am J Pathol. 2013;182(5):1811-20.
https://doi.org/10.1016/j.ajpath.2013.01.018 DOI: https://doi.org/10.1016/j.ajpath.2013.01.018
Okajima E, Hiramatsu T, Iriya K, Ijuin M, Matsushima S, Yamada K. Effects of sex-hormones on development of urinary-bladder tumors in rats induced by N-BUTYL-N-(4-hydroxybutyl) Nitrosamine. Urol Res. 1975;3(2):73–9.
https://doi.org/10.1007/BF00256185 DOI: https://doi.org/10.1007/BF00256185
Bertram JS, Craig AW. Specific induction of bladder cancer in mice by butyl-(4-hydroxybutyl)-nitrosamine and the effects of hormonal modifications on the sex difference in response. Eur J Cancer (1965). 1972;8(6):587–94.
https://doi.org/10.1016/0014-2964(72)90137-5 DOI: https://doi.org/10.1016/0014-2964(72)90137-5
Tanahashi NK, Suzawa N, Azuma C. Effects of sex hormones on oncogenesis in rat urinary bladder by N-butyl-N-(4-hydroxybutyl)-nitrosamine. Int J Clin Pharmacol Biopharm. 1977;15(3):101–5.
Gil D, Zarzycka M, Dulińska-Litewka J, Ciołczyk-Wierzbicka D, Lekka M, Laidler P. Dihydrotestosterone increases the risk of bladder cancer in men. Hum Cell. 2019;32(3):379–89.
https://doi.org/10.1007/s13577-019-00255-3 DOI: https://doi.org/10.1007/s13577-019-00255-3
Vermeulen SH, Hanum N, Grotenhuis AJ, Castaño-Vinyals G, Van Der Heijden AG, Aben KK, et al. Recurrent urinary tract infection and risk of bladder cancer in the Nijmegen bladder cancer study. Br J Cancer. 2015;112(3):594–600.
https://doi.org/10.1038/bjc.2014.601 DOI: https://doi.org/10.1038/bjc.2014.601
Additional Files
Published
How to Cite
License
Copyright (c) 2023 Josephine M. Hyldgaard, Mette Nørgaard, Peter E. Hjort, Jørgen B. Jensen
This work is licensed under a Creative Commons Attribution 4.0 International License.
