ASCO PROSTATE: Cardiac Risks of Androgen Deprivation Emerge

February 26, 2007

KISSIMMEE, Fla. -- Androgen deprivation for prostate cancer in men older than 65 may contribute to increased cardiac mortality, suggested a retrospective analysis of registry data.

KISSIMMEE, Fla., Feb. 26 -- Androgen deprivation for prostate cancer in men older than 65 may contribute to increased cardiac mortality, suggested a retrospective analysis of registry data.

The risk of dying from a cardiac cause for men older than 65 who were taking androgen deprivation therapy was 3% over five years compared to 0.0% for same-age prostate cancer patients who did not receive the therapy (P=0.004), said Henry Tsai, M.D., a Harvard radiation oncologist.

By comparison, androgen therapy was not associated with a significant increase in cardiac mortality for men younger than 65 (1.5% versus 0.3%, P=0.8), Dr. Tsai reported at a prostate cancer symposium here.

Dr. Tsai pointed out that it is well known from prior studies that androgen therapy is associated with increased body mass index, increased adiposity, dyslipidemia, and diabetes -- all of which are significant risk factors for cardiovascular disease.

Nonetheless, he noted that because his study was a retrospective analysis the findings should be considered hypothesis-generating and a prospective clinical trial is needed to confirm a cause-and-effect relationship.

He identified 3,636 men with localized disease from the CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) database, a national registry of men with prostate cancer, who were free of cardiovascular disease at time of initial treatment. The median age of the men was 64.

Of those men 735 men received androgen deprivation therapy for at least four months (treatment range one month to 32.9 months) and 2,901 patients did not.

After controlling for age and cardiovascular disease risk factors, only two factors -- duration of androgen deprivation therapy and age -- were significant predictors of cardiac mortality at five years, he said.

Moreover, after additionally controlling for pre-treatment prostate specific antigen (PSA) level, Gleason score, and tumor stage, "duration of androgen therapy was also associated with shorter time to cardiac mortality and shorter time to all-cause mortality."

"Frankly, I was surprised by the outcomes of this study," commented Cleveland Clinic urologic oncologist Eric Klein, M.D., who moderated a press conference where Dr. Tsai discussed his findings.

"We knew that as little as three to six months of androgen deprivation therapy resulted in some increases in body weight, bone loss and some cognitive difficulties in some men, but we didn't know it killed people," Dr. Klein said.

Dr. Klein said that clinicians would need to carefully assess patients -- especially older patients -- for cardiovascular risk factors before initiating androgen deprivation therapy.

Dr. Klein suggested that it might be necessary to consider combining androgen deprivation with drugs used to prevent cardiovascular events such as low-dose aspirin, or statins, to control lipid changes associated with androgen therapy. But he cautioned that there could be drug-drug interactions between anti-hormone therapy and antiplatelet or lipid-lowering agents.

"I don't know why these drugs should interact but we won't know until we do those studies," Dr. Klein said.

The CaPSURE registry is funded by TAP Pharmaceutical Products, Inc., of Lake Forest, Ill. Neither Dr. Tsai nor Dr. Klein reported any conflicts.