No Increased Risk of Cardiovascular Death With Androgen Deprivation Therapy for Prostate Cancer

Paul L. Nguyen, MD

New results from a meta-analysis show no apparent association between androgen deprivation therapy (ADT) and cardiovascular events and death in men with prostate cancer.

The findings are from pooled data from 8 prospective randomized trials comparing immediate gonadotropin- releasing hormone (GnRH) agonist-based ADT versus no ADT or deferred ADT in a total of 4141 men with nonmetastatic, unfavorable-risk prostate cancer. The median length of follow-up was 7.6 to 13.2 years.

“Our study suggests that for the population as a whole, there is either no adverse effect of ADT on cardiovascular mortality or the magnitude of this effect is likely rather small,” said Paul L. Nguyen, MD, director of Prostate Brachytherapy and Clinical Trials for Genitourinary Radiation Oncology at the Dana- Farber Cancer Institute, and assistant professor in the Department of Radiation Oncology at Harvard Medical School in Boston, Massachusetts, and associates.

Androgen deprivation therapy in the form of a GnRH agonist is a treatment mainstay for prostate cancer. However, several studies have reported that ADT may increase the risk of cardiovascular death in this population.

As a result, the American Heart Association, the American Cancer Society, the American Urological Association, and the American Society of Radiation Oncology issued a joint advisory in 2010 intended to boost awareness about a possible association between ADT and cardiovascular events and death. The FDA also released a safety warning requiring GnRH manufacturers to include in their labeling a warning about the potential for such a link.

Because other studies did not confirm the findings coupled with ongoing significant “clinical concern over this issue,” Nguyen and colleagues decided to conduct a meta-analysis to provide a more definitive answer on whether ADT causes excess cardiovascular deaths in men with prostate cancer.

Among the 2200 patients who were treated with ADT, there were 255 cardiovascular deaths, for an overall incidence of cardiovascular death of 11.0% (95% CI, 8.3% -14.5%). In the control group, there were 1941 patients and 252 cardiovascular deaths, for an overall incidence of 11.2% (95% CI, 8.3%-15.0%; RR, 0.93; 95% CI, 0.79-1.10; P = .41).

“

Our study suggests that for the population as a whole, there is either no adverse effect of ADT on cardiovascular mortality or the magnitude of this effect is likely rather small. ”

—Paul L. Nguyen, MD

The investigators were unable to identify a single subgroup in which ADT was associated with excess cardiovascular mortality. The subgroups they examined included men receiving short-course ADT (≤6 mo), men receiving long-course ADT (≥3 y), men receiving radiation, and men ≥70 years of age.

The study did find, however, that the use of ADT in men with unfavorable-risk prostate cancer was significantly associated with improved prostate cancerspecific and overall survival.

Nguyen and colleagues noted that while the findings should be reassuring for most men considering the use of ADT for aggressive prostate cancer, randomized trials whereby patients are stratified by preexisting cardiovascular comorbidity are needed to determine whether the findings will hold true for individuals with a prior history of congestive heart failure or myocardial infarction.

Nguyen PL, Je Y, Schutz FA, et al. Association of androgen deprivation therapy with cardiovascular death in patients with prostate cancer: a meta-analysis of randomized trials. JAMA. 2011;306(21):2359-2366.