Advertisement
Advanced Disease| Volume 155, P186-191, September 2021

Download started.

Ok

Beta-Adrenergic Antagonists and Cancer Specific Survival in Patients With Advanced Prostate Cancer: A Veterans Administration Cohort Study

Published:February 12, 2021DOI:https://doi.org/10.1016/j.urology.2021.02.008

      Objective

      To interrogate the National Veterans Health Administration (VA) database to determine if beta-blocker use at time of initiation of androgen therapy deprivation (ADT) would result in improved oncological outcomes in advanced prostate cancer (PCa).

      Methods

      All men diagnosed with high risk PCa (PSA >20) from 2000-2008 who were on ADT ≥ 6 months were identified. Patients receiving ADT concurrently with primary radiation therapy were excluded. Pharmacy data was interrogated for all beta-blockers, but then focused on the selective beta-1 blocker metoprolol. Cox proportional hazards ratios were calculated for overall survival (OS), PCa specific survival (CSS) and skeletal related events (SREs).

      Results

      In 39,198 patients with high risk PCa on ADT, use of any beta-blocker was not associated with improvement in OS, CSS, or SREs. Further analyses focusing on metoprolol found that 10,224 (31.9%) had used metoprolol while 21,834 had no beta-blocker use. Multivariable analysis with Inverse Propensity Score Weighting, adjusted for factors including PSA, Gleason score, and duration ADT, found that utilization of metoprolol was not associated with improvement in OS (hazard ratio [HR] 0.97, P = .19), CSS (HR 0.94, P = .23) or SREs (HR 0.98, P = .79).

      Conclusion

      In this large cohort, metoprolol use in conjunction with ADT in high risk PCa was not associated with improvement in OS, CSS, or risk of SRE. In contrast to a recent smaller clinical study, our data strongly suggests no cancer specific benefit to beta-blocker use in advanced PCa.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Urology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Key Statistics for Prostate Cancer | Prostate Cancer Facts. Accessed July 9, 2020. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.

      2. Prostate Cancer: Castration Resistant Guideline - American Urological Association. Accessed July 9, 2020. https://www.auanet.org/guidelines/prostate-cancer-castration-resistant-guideline

        • Léauté-Labrèze C
        • de la Roque ED
        • Hubiche T
        • Boralevi F
        • Thambo J-B
        • Taïeb A
        Propranolol for severe hemangiomas of infancy.
        N Engl J Med. 2008; 358: 2649-2651https://doi.org/10.1056/NEJMc0708819
        • Rotter A
        • Oliveira ZNP de
        Infantile hemangioma: pathogenesis and mechanisms of action of propranolol.
        JDDG J Dtsch Dermatol Ges. 2017; 15: 1185-1190https://doi.org/10.1111/ddg.13365
        • Fitzgerald PJ
        Is norepinephrine an etiological factor in some types of cancer?.
        Int J Cancer. 2009; 124: 257-263https://doi.org/10.1002/ijc.24063
        • Zahalka AH
        • Arnal-Estapé A
        • Maryanovich M
        • et al.
        Adrenergic nerves activate an angio-metabolic switch in prostate cancer.
        Science. 2017; 358: 321-326https://doi.org/10.1126/science.aah5072
        • Palm D
        • Lang K
        • Niggemann B
        • et al.
        The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by β-blockers.
        Int J Cancer. 2006; 118: 2744-2749https://doi.org/10.1002/ijc.21723
      3. Sympathetic nervous system induces a metastatic switch in primary breast cancer. Accessed July 9, 2020. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2940980/

        • Cole SW
        • Sood AK
        Molecular pathways: Beta-adrenergic signaling in cancer.
        Clin Cancer Res. 2012; 18: 1201-1206https://doi.org/10.1158/1078-0432.CCR-11-0641
        • Akbar S
        • Alsharidah MS
        Are beta blockers new potential anticancer agents?.
        Asian Pac J Cancer Prev. 2014; 15: 9567-9574https://doi.org/10.7314/APJCP.2014.15.22.9567
        • Grytli HH
        • Fagerland MW
        • Fosså SD
        • Taskén KA
        Association between use of β-Blockers and prostate cancer–specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease.
        Eur Urol. 2014; 65: 635-641https://doi.org/10.1016/j.eururo.2013.01.007
        • Price LE
        • Shea K
        • Gephart S
        The Veterans Affairs's Corporate Data Warehouse: Uses and implications for nursing research and practice.
        Nurs Adm Q. 2015; 39: 311-318https://doi.org/10.1097/NAQ.0000000000000118
      4. Webmaster PBM. Pharmacy Benefits Management Services Home. Accessed July 9, 2020. https://www.pbm.va.gov/

        • Friedman GD
        • Udaltsova N
        • Habel LA
        Norepinephrine antagonists and cancer risk.
        Int J Cancer. 2011; 128 (author reply 739): 737-738https://doi.org/10.1002/ijc.25351
      5. Healthcare D. Medical Claims Data & Insights| Definitive Healthcare. Accessed July 9, 2020. https://www.definitivehc.com/platform/data/medical-claims

        • Aly A
        • Onukwugha E
        • Woods C
        • et al.
        Measurement of skeletal related events in SEER-Medicare: a comparison of claims-based methods.
        BMC Med Res Methodol. 2015; 15: 65https://doi.org/10.1186/s12874-015-0047-5
        • Coleman RE
        Clinical features of metastatic bone disease and risk of skeletal morbidity.
        Clin Cancer Res Off J Am Assoc Cancer Res. 2006; 12: 6243s-6249shttps://doi.org/10.1158/1078-0432.CCR-06-0931
        • Ritch CR
        • Graves AJ
        • Keegan KA
        • et al.
        Increasing use of observation among men at low risk for prostate cancer mortality.
        J Urol. 2015; 193: 801-806https://doi.org/10.1016/j.juro.2014.08.102
        • HE P
        • ERIKSSON F
        • SCHEIKE TH
        • ZHANG M-J
        A proportional hazards regression model for the sub-distribution with covariates adjusted censoring weight for competing risks data.
        Scand J Stat Theory Appl. 2016; 43: 103-122https://doi.org/10.1111/sjos.12167
        • Ruan PK
        • Gray RJ.
        Analyses of cumulative incidence functions via non-parametric multiple imputation.
        Stat Med. 2008; 27: 5709-5724https://doi.org/10.1002/sim.3402
        • Anderson-Carter I
        • Posielski N
        • Liou J-I
        • et al.
        The impact of statins in combination with androgen deprivation therapyin patients with advanced prostate cancer: A large observational study.
        Urol Oncol. 2019; 37: 130-137https://doi.org/10.1016/j.urolonc.2018.11.017
        • Heinze G
        • Jüni P
        An overview of the objectives of and the approaches to propensity score analyses.
        Eur Heart J. 2011; 32: 1704-1708https://doi.org/10.1093/eurheartj/ehr031
        • Assayag J
        • Pollak MN
        • Azoulay L
        Post-diagnostic use of beta-blockers and the risk of death in patients with prostate cancer.
        Eur J Cancer Oxf Engl 1990. 2014; 50: 2838-2845https://doi.org/10.1016/j.ejca.2014.08.006
        • Cardwell CR
        • Coleman HG
        • Murray LJ
        • O'Sullivan JM
        • Powe DG
        Beta-blocker usage and prostate cancer survival: a nested case-control study in the UK Clinical Practice Research Datalink cohort.
        Cancer Epidemiol. 2014; 38: 279-285https://doi.org/10.1016/j.canep.2014.03.011
      6. Bhaskaran K, Rachet B, Evans S, Smeeth L. Re: Helene Hartvedt Grytli, Morten Wang Fagerland, Sophie D. Fosså, Kristin Austlid Taskén. Association between use of β-blockers and prostate cancer–specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.01.007.: Beta-blockers and Prostate Cancer Survival – Interpretation of Competing Risks Models. Eur Urol. 2013;64(4):e86-e87. doi:10.1016/j.eururo.2013.07.004

      7. Cardwell CR, Suissa S, Murray LJ. Re: Helene Hartvedt Grytli, Morten Wang Fagerland, Sophie D. Fosså, Kristin Austlid Taskén. Association between use of β-Blockers and prostate cancer–specific survival: a cohort study of 3561 prostate cancer patients with high-risk or metastatic disease. Eur Urol. In press. http://dx.doi.org/10.1016/j.eururo.2013.01.007. Eur Urol. 2013;64(1):e10. doi:10.1016/j.eururo.2013.03.046

        • Richards KA
        • Liou J-I
        • Cryns VL
        • Downs TM
        • Abel EJ
        • Jarrard DF
        Metformin use is associated with improved survival for patients with advanced prostate cancer on androgen deprivation therapy.
        J Urol. 2018; 200: 1256-1263https://doi.org/10.1016/j.juro.2018.06.031
        • Grytli HH
        • Fagerland MW
        • Fosså SD
        • Taskén KA
        • Håheim LL
        Use of β-blockers is associated with prostate cancer-specific survival in prostate cancer patients on androgen deprivation therapy.
        The Prostate. 2013; 73: 250-260https://doi.org/10.1002/pros.22564