Introduction:
Development of castration resistant prostate cancer (CRPC) is characterized by alterations in tumor cell signaling and metabolism which represent an opportunity for synergistic therapies to supplement androgen deprivation therapy (ADT) and delay disease progression. Recent work in Science found that endothelial β-adrenergic receptor signaling in the prostate stroma is critical for activation of an angiogenic switch and tumor progression suggesting an inhibitory role for beta-blockers (Zahalka, 2017). Epidemiological studies have shown a possible association between beta blocker use and improved prostate cancer (PCa) specific survival, but the data is limited and conflicting. To evaluate the role of selective beta-blocker use in advanced PCa, we interrogated the National Veterans Health Administration (VA) database to determine if metoprolol use at time of ADT initiation would result in improved oncologic outcomes.
Methods:
We identified all men diagnosed with PCa in the VA Corporate Data Warehouse (CDW) from 2000 to 2008 and obtained pharmacy data for those with PSA >20 that initiated ADT during this time (n=39,198). Patients receiving ≤ 6 months of ADT or ADT concurrently with primary radiation therapy were excluded. Pharmacy data was queried for use of metoprolol, a beta-1 selective beta blocker. Cox proportional hazards ratios were calculated for overall survival (OS), PCa specific survival (CSS) and skeletal related events (SREs).
Results:
Of the final cohort of 39,198 patients with PCa on ADT and PSA >20, 10,223 (26.1%) had used metoprolol while 28,975 (73.9%) had not. Multivariable analysis found that utilization of metoprolol was not associated with improvement in OS (HR 0.97, CI 0.93-1.02, p=0.244) or CSS (HR 0.94, CI 0.85-1.04 p=0.213). When competing risk analysis was performed to account for death from other causes, metoprolol had no effect on PCa specific death (HR 0.98, CI 0.89-1.08, p=0.673). Metoprolol use was also not predictive of increased SREs (HR 1.0, CI 0.87-1.15, p=0.971).
Conclusion:
In the largest cohort to date, metoprolol use in conjunction with ADT for advanced PCa was not associated with improvement in OS, CSS or risk of SREs. Our study suggests no survival benefit to beta blockers in advanced PCa. The role of these agents in limiting disease progression via blocking endothelial β-adrenergic receptor signaling in the prostate stroma in early PCa is being investigated.
Funding: N/a
UNDERSTANDING THE ROLE OF SELECTIVE BETA-BLOCKERS IN PATIENTS WITH ADVANCED PROSTATE CANCER ON ANDROGEN DEPRIVATION THERAPY.
Category
Prostate Cancer > Other
Description
Poster #87 / Podium #
Poster Session I
12/4/2019
2:00 PM - 5:30 PM
Presented By: Natasza Posielski
Authors:
Natasza Posielski
Kyle Richards
Jinn-ing Liou
E. Jason Abel
Tracy Downs
Tudor Borza
David Jarrard