Androgen deprivation therapy (ADT) with gonadotropin-releasing hormone (GnRH) agonists is associated with an increased risk of cardiac events in elderly men with localized prostate cancer and a decent life expectancy, new findings suggest.
“Clinicians should carefully weigh the risks and benefits of ADT in patients with a prolonged life expectancy,” the authors concluded in a paper published online ahead of print in BJU International. “Routine screening and lifestyle interventions are warranted in at-risk subpopulations treated with ADT.”
Guidelines support ADT as an adjunct to radiotherapy for men with high-risk and locally advanced PCa, but do not recommend it as a primary treatment for low-risk PCa, they noted. Various large observational studies have demonstrated associations between ADT and an elevated risk of cardiovascular morbidity.
Using the Surveillance, Epidemiology and Ed Results (SEER) database, Marianne Schmid, MD, of Brigham and Women's Hospital and Harvard Medical School in Boston, and collaborators identified 50,384 men diagnosed with localized prostate cancer (PCa) and compared those who received either GnRH agonists or orchiectomy within 2 years and 6 months of PCa diagnosis, respectively, and those who did not. The investigators stratified GnRH use using monthly equivalent doses (less than 8 or 8 or more doses). They stratified patients according to life expectancy: less than 5 years, 5–10 years, and more than 10 years. In addition, the investigators examined the effect of ADT on overall cardiac events, coronary heart disease (CHD), acute myocardial infarction (AMI), and sudden cardiac death (SCD).
Overall, the proportion of patients experiencing cardiac events was significantly greater among those receiving GnRH agonists than those not receiving the medications (42% vs. 38.6%), the investigators reported. Compared with men not treated with GnRH agonists, those who received fewer than 8 doses and 8 or more doses had a significant 13% and 18% increased risk of any cardiac event, respectively, in adjusted analyses. Additionally, men who received fewer than 8 and 8 or more doses of GnRH agonists had a significant 13% and 17% increased risk of CHD. Only patients who had a life expectancy of 5–10 years and received fewer than 8 doses of GnRH agonists had a significantly elevated risk of AMI.
Results showed that the effect of prolonged GnRH agonist use on cardiac event risk was sustained across all strata of life expectancy. Researchers, however, observed no effect among patients with a life expectancy of less than 5 years and whose GnRH agonist use was limited to fewer than 8 doses. In addition, men who received 8 or more doses of GnRH agonists and had a life expectancy of 5 or more years had a significantly higher risk of sudden cardiac death.
Orchiectomy was not associated with overall cardiac events, AMI, or SCD, and was protective against cardiac-related interventions, Dr. Schmid's group reported.
“Taken together, our findings suggest that patients with longer life expectancy are most at risk of cardiac morbidity after ADT administration,” the authors wrote. “In consideration of previous reports and our study findings, it is worrying and disappointing that one in three patients still receives primary ADT as the sole treatment for localized PCa.”
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