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Kokorovic et al

PRONOUNCE is a multi-institutional, international, pro- were followed by a cardiologist and underwent cardiac opti-
spective, randomized controlled trial whose primary end- mization for secondary prevention of cardiac events. This
point was to compare the effect of degarelix and leupro- strongly suggests that routine monitoring of adverse events
lide on MACE in patients with prostate cancer and a prior and optimization of cardiac risk factors throughout ADT
history of atherosclerotic cardiovascular disease (ASCVD). treatment may reduce cardiac morbidity associated with
Patients due to receive ADT for a minimum duration of 12 ADT. This supports the guideline panel’s recommendations
months were randomized to receive degarelix or leuprolide for continuous monitoring and optimization of cardiometa-
in standard doses. The primary endpoint of the study was bolic parameters in patients receiving ADT, regardless of
the time from randomization to first occurrence of centrally whether an agonist or antagonist is used.
adjudicated MACE, a composite of all-cause death, MI, or
stroke through 12 months. Competing interests: Dr. So has been an advisory board member for Abbvie, Amgen, Astellas,
The primary outcome of first occurrence of MACE (all- Bayer, Janssen, Ferring, and TerSera; and has participated in clinical trials supported by Astellas,
cause death, MI, or stroke) occurred in 15 (5.5%) patients Ferring, and Janssen. Dr. Izard has received grant(s) or honoraria from Abbvie, Astellas, Bayer,
receiving degarelix and 11 (4.1%) patients receiving leu- Ferring, Janssen, and Sanofi; and has participated in clinical trials supported by Abbvie, Astellas,
prolide (hazard ratio [HR] 1.28, 95% confidence interval AstraZeneca, Bayer, Janssen, and Merck. Dr. Saad has been an advisory board member for and has
received payment/honoraria from Abbvie, Amgen, Astellas, Bayer, Janssen, and Sanofi; and has
[CI] 0.59–2.79, p=0.53). Additional prespecified sensitivity participated in clinical trials supported by Amgen, Astellas, Bayer, Janssen, and Sanofi. Dr. Shayegan
analyses and secondary endpoints were analyzed, none of has been an advisory board member for Astellas, Bayer, and Janssen; and has received a research
which yielded a difference in event rate between the groups. grant from Janssen. Dr. Aprikian has been an advisory board member for Abbvie, Astellas, and
Importantly, using the HERO trial definitions for MACE, Bayer; and has received grants from Abbvie, Astellas, Bayer, Sanofi, and TerSera. Dr. Rendon has
3
there were 18 events in the degarelix group compared to 21 been an advisory board and speakers’ bureau member for and has received honoraria from Abbvie,
events in the leuprolide group (HR 0.81, 95% CI 0.43–1.53). Amgen, Astellas, AstraZeneca, Bayer, Ferring, Jansen, and Sanofi. The remaining authors report no
PRONOUNCE is the first international, multi-institutional, competing personal or financial interests related to this work.
randomized controlled trial that prospectively compares the
cardiovascular risk of a GnRH antagonist vs. an agonist in
men with prostate cancer. Overall, the trial results suggest Prior to publication, this guideline update was reviewed and approved by the CUA Guidelines
there is no added cardiovascular risk in men receiving a Committee and the CUA Board of Directors.
GnRH agonist compared to an antagonist.
The trial has two major limitations. First, patient accrual
closed early, with only approximately 60% of the targeted References
number of patients accrued. Second, the event rate was
much lower than anticipated (4.8% actual event rate vs. 1. Kokorovic A, So AI, Serag H, et al. Canadian Urological Association guideline on androgen depriva-
7.5% anticipated). PRONOUNCE is, therefore, under- tion therapy: Adverse events and management strategies. Can Urol Assoc J 2021;15:E307-22.
http://dx.doi.org/10.5489/cuaj.7355
powered to demonstrate a significant difference in the pri- 2. Lopes RD, Higano CS, Slovin SF, et al. Cardiovascular safety of degarelix vs. leuprolide in patients with
mary event rate. prostate cancer: The primary results of the PRONOUNCE randomized trial. Circulation 2021;144:1295-
Nonetheless, there is key take-away point from the 1307. https://doi.org/10.1161/CIRCULATIONAHA.121.056810
PRONOUNCE study. The overall event rate was low in both 3. Shore ND, Saad F, Cookson MS, et al. Oral relugolix for androgen deprivation therapy in advanced prostate
groups at 4.8%, and was, in fact, much lower than what was cancer. N Engl J Med 2020;382:2187-96. https://doi.org/10.1056/NEJMoa2004325
observed in the HERO trial, where 17.8% of patients with
prior MACE receiving leuprolide experienced an additional Correspondence: Dr. Ricardo Rendon, Department of Urology, Dalhousie, University, Halifax, NS,
Canada; rrendon@dal.ca
MACE on trial. The lower event rate in PRONOUNCE can
likely be attributed to the fact that all enrolled participants

244 CUAJ • August 2022 • Volume 16, Issue 8