Androgen deprivation therapy (ADT) is a common treatment for prostate cancer that is used when the tumour has progressed or is likely to return after surgery or radiation. Doctors use ADT (also known as hormonal treatment) to block testosterone from fueling prostate cancer development. However, this type of therapy has possible adverse effects, including heart effects that should be properly watched, especially in men with cardiovascular disease or other cardiac risk factors. Every year, approximately one million men are diagnosed with prostate cancer throughout the world, and half of them will be prescribed ADT at some point in their lives.
Clinical trials are now being conducted to determine if certain kinds of ADT are safer for the heart than others. In August, the long-awaited findings of the first such experiment were released. However, the experiment was terminated early due to low enrollment, and as a result, physicians did not receive the definitive response they were hoping for.
An international team of urologists, oncologists, and cardiologists led the PRONOUNCE study, which began in May 2016. Two different drugs were evaluated. Leuprolide (Lupron) is one of them, and it belongs to the family of luteinizing hormone-releasing hormone (LHRH) agonists. This form of ADT works by activating the pituitary gland in the brain, which then sends instructions to other glands, causing a testosterone spike. Testosterone levels drop dramatically after a few weeks of therapy. The other medication, degarelix, belongs to a family of GNRH antagonists known as gonadotropin-releasing hormone (GNRH) antagonists. Degarelix is a monthly injectable that works on the pituitary gland but does not produce a testosterone surge. Degarelix is used far less often than leuprolide, and preliminary research shows it may have a superior cardiovascular profile.
The goal of the investigation was to enrol 900 men with prostate cancer and a history of cardiovascular disease from 12 different countries. Men with newly diagnosed high- or moderate-risk prostate cancer who received ADT coupled with radiation, as well as men who received ADT for cancer that was considered to be returning after initial therapy, were among the study's participants. For at least a year, all of the men were randomized to receive either leuprolide or degarelix, with the goal of comparing their rates of heart attack, stroke, or death from any cause.
Only 545 men have registered in PRONOUNCE and completed a year of ADT by April 2020. There were no significant changes in the number of cardiovascular events or deaths between the two groups, according to the researchers. In the leuprolide group, there were 11 (4.1%) such occurrences, whereas in the degarelix group, there were 15 (5.5%). Drugs like statins and beta blockers were being used to treat many of the men for heart disease. Enrollment slowed in part due to changes in the standard of care, including as the availability of newer types of ADT, such as abiraterone, which made assessing cardiac risks from either leuprolide or degarelix alone difficult.
Marc Garnick, M.D., the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, editor of the Harvard Health Publishing Annual Report on Prostate Diseases, and editor in chief of HarvardProstateKnowledge.org, has provided the following response.
"The data is still unclear, and these findings, which are based on incomplete research with fewer people than expected, don't provide any more clarity. The initial hypothesis was that degarelix would have fewer cardiovascular adverse effects than leuprolide, however, PRONOUNCE data suggests otherwise. What's crucial to remember is that men with prostate cancer who take any of these medicines are at risk for cardiovascular complications. Before administering these essential medicines, oncologists and urologists alike should examine pre-existing cardiac history. The advantages of ADT exceed the dangers for individuals with advanced prostate cancer. However, the necessity for these medicines is less definite for people with less aggressive forms of prostate cancer. We should proceed with caution and constantly monitor patients for any symptoms of cardiac adverse effects, especially if they have a history of cardiovascular illness."
