Cookson, assistant and armchair of urology at the University of Oklahoma College of Medicine, Oklahoma City, is coeditor in arch for Urology Times®.
Unquestionably, the mainstay of analysis for men with avant-garde and metastatic prostate blight is androgen denial analysis (ADT). The benign aftereffect of ADT on authoritative prostate blight has been axiomatic for added than 70 years afterward the beat assignment of Huggins and Hodges.1 Atherosclerotic cardiovascular ache (ASCVD) is the arch account of noncancer afterlife in men with prostate cancer, and abounding men with avant-garde prostate blight anchorage cardiovascular accident factors.2 Although the allowances of ADT are not accustomed and the accident of ASCVD is acknowledged, there is altercation surrounding the about cardiovascular assurance of gonadotropin-releasing hormone (GnRH) antagonists compared with the GnRH agonists in men with prostate blight and ASCVD advised with these agents.
To highlight this controversy, 2 important analytic trials afresh appear are aces of mention. In the PRONOUNCE balloon (NCT02663908), an all-embracing multicenter -to-be study, men with prostate blight and ASCVD were randomized to accept the GnRH adversary degarelix or the GnRH agonist leuprolide for 12 months.3 The primary aftereffect was the time to aboriginal above adverse cardiovascular accident (MACE). The abstraction was assured aboriginal because of the slower than projected acceptance and beneath than advancing primary aftereffect events. Overall, there was no aberration in MACE at 1 year amid patients assigned to degarelix and those who accustomed leuprolide (5.5% vs 4.1%, respectively; P = .534). The authors assured that the about cardiovascular assurance of GnRH antagonists and agonists charcoal unresolved.
In contrast, in the appearance 3 HERO abstraction (NCT03085095), patients with avant-garde prostate blight were about assigned in a 2:1 arrangement to accept relugolix (Orgovyx), an articulate GnRH antagonist, or leuprolide for 48 weeks.4 The primary end point was abiding testosterone abolishment to alter levels through 48 weeks, and the abstraction met this end point. Of men who accustomed relugolix, 96.7% maintained castration through 48 weeks compared with 88.8% of men accepting leuprolide. Amid all patients, accident of MACE was 2.9% in the relugolix accumulation and 6.2% in the leuprolide group. The authors assured that relugolix accomplished rapid, abiding abolishment of testosterone levels that was above to that with leuprolide, with a 54% lower accident of MACE.
So what explains the aberration amid these 2 studies? One achievability is that the abstract differences in assurance amid these agents is not as clinically allusive in accepted practice. There could additionally be differences in injectable vs articulate GnRH antagonists. Addition achievability is that in the PRONOUNCE study, in which the patients had accepted cardiovascular accident factors, cardiovascular contest ability accept been lower because of bigger acquaintance and absorption to cardiovascular accident control. In contrast, although patients who accomplished MACE aural 6 months afore balloon admission were afar in the HERO trial, apparently accepted cardiovascular accident ascendancy would not accept been so carefully scrutinized. At a minimum, bigger absorption to the cardiovascular accident factors amid men with avant-garde prostate cancer, including those advised with ADT, will advance outcomes and abate MACE. And conceivably there is addition Nobel Prize cat-and-mouse to be had if we could abate the cardiovascular aftereffect of ADT and alleviate the acknowledgment to the altercation surrounding the allusive assurance and appulse on cardiovascular bloom amid GnRH agonists and antagonists.
1. Corbin NS, Thompson I. Urology and the Nobel Prize. Urol Oncol. 2003;21(1):83–85. doi:10.1016/s1078-1439(03)00002-4
2. Leong DP, Fradet V, Shayegan B, et al. Cardiovascular accident in men with prostate cancer: insights from the RADICAL PC Study. J Urol. 2020;203(6):1109-1116. doi:10.1097/JU.0000000000000714
3. Lopes RD, Higano CS, Slovin SF, et al. Cardiovascular assurance of degarelix against leuprolide in patients with prostate cancer: the primary after-effects of the PRONOUNCE randomized trial. Circulation. Appear online August 30, 2021. doi:10.1161/circulationaha.121.056810
4. Shore ND, Saad F, Cookson MS, et al. Articulate relugolix for androgen-deprivation analysis in avant-garde prostate cancer. New Engl J Med. 2020;382(23):2187-2196. doi:10.1056/NEJMoa2004325
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