Understanding ADT and Cardiovascular Risks

Clinicians managing prostate cancer often rely on androgen deprivation therapy (ADT) to control disease progression. However, this treatment frequently correlates with an increased risk of cardiovascular morbidity. Consequently, the biological mechanism behind this risk has become a primary focus for researchers. Recent evidence suggests that coronary plaque progression serves as a vital indicator of these adverse cardiac outcomes. Specifically, a new randomized clinical trial compares how different ADT classes influence the growth of arterial plaque over twelve months.

Accelerated Coronary Plaque Progression with Leuprolide

The REVELUTION trial investigated sixty-five men with nonmetastatic prostate cancer. These participants received either the GnRH agonist leuprolide or the GnRH antagonist relugolix. Furthermore, researchers used advanced coronary computed tomographic angiography to measure changes in plaque volume. The results showed that leuprolide was associated with a significantly greater 12-month increase in total plaque volume. In contrast, patients treated with relugolix experienced much slower coronary plaque progression during the same period.

Moreover, the study highlighted that this growth was largely driven by noncalcified plaque volume. This finding is particularly concerning because noncalcified plaques are often more unstable and prone to rupture. Therefore, the choice of ADT may directly influence the stability of a patient's cardiovascular health. Additionally, adjusting for statin use and baseline plaque volume did not change the significance of these findings. Leuprolide consistently demonstrated a more aggressive impact on the coronary arteries than its antagonist counterpart.

Clinical Implications for Prostate Cancer Management

For oncologists and urologists, these findings provide a mechanistic basis for the cardiac safety profiles observed in earlier trials like HERO. Selecting a GnRH antagonist might mitigate the accelerated coronary plaque progression seen with traditional agonists. Consequently, physicians should consider individual cardiovascular risk factors when prescribing ADT. Transitioning to antagonists could potentially offer a safer pathway for men with pre-existing atherosclerosis or high cardiac risk. Ultimately, this trial underscores the importance of cardio-oncology collaboration in modern cancer care.

Frequently Asked Questions

Why does leuprolide cause more plaque growth than relugolix?

While the exact mechanism is still being studied, researchers believe that GnRH agonists like leuprolide may cause different downstream immune responses and hormonal fluctuations compared to antagonists. These variations potentially accelerate the development of unstable, noncalcified plaques.

What is the clinical significance of noncalcified plaque in these patients?

Noncalcified plaque is highly associated with a greater risk of acute coronary syndromes. Because leuprolide specifically increases this type of plaque, it may explain why some patients experience higher rates of major adverse cardiovascular events during treatment.

Should all prostate cancer patients be screened for coronary plaque?

Current guidelines emphasize assessing baseline cardiovascular risk. While routine CCTA is not yet standard for every patient, those with high risk factors may benefit from closer monitoring and the use of ADT options that minimize plaque progression.

Disclaimer: This content is for informational and educational purposes only. It does not constitute medical advice or a professional relationship. Refer to the latest local and national guidelines for clinical practice.

References

Patel SA et al. Coronary Plaque Progression After Androgen Deprivation Therapy in Men With Prostate Cancer: A Randomized Clinical Trial. JAMA Cardiol. 2026 Feb 18. doi: 10.1001/jamacardio.2025.5586. PMID: 41706486.

Shore ND, et al. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020;382:2187-2196.

Klaassen Z, et al. Society of Urologic Oncology (SUO) 2025 Abstract: REVELUTION trial results. urotoday.com.