For Prostate Cancer, Surgery Plus Androgen Deprivation Raises Cardiovascular Mortality

BOSTON, Oct. 10 -- When androgen deprivation for localized prostate cancer is combined with a radical prostatectomy, the risk of a cardiovascular death appears to more than double, researchers here said.

Men who had adjuvant or neo-adjuvant androgen deprivation therapy along with surgery had 2.6 times the risk of cardiovascular death as men who had surgery alone, found radiation oncologist Henry Tsai, M.D., of Harvard Medical School, and colleagues.

On the other hand, androgen deprivation therapy combined with non-surgical treatments for localized prostate cancer did not increase the risk, Dr. Tsai and colleagues reported in the Oct. 17 issue of the Journal of the National Cancer Institute.

The finding came as androgen deprivation therapy -- treatment with a gonadotropin-releasing hormone agonist and/or an antiandrogen -- is increasing, Dr. Tsai and colleagues said.

The use of the therapy is associated with an elevated body mass index, increased fat deposition, and decreased insulin sensitivity, the researchers noted. These are all elements of the metabolic syndrome, which predisposes to diabetes and coronary artery disease.

Dr. Tsai and colleagues analyzed the database of the Cancer of the Prostate Strategic Urologic Research Endeavor study, a longitudinal, observational disease registry of more than 13,000 patients with biopsy-proven prostate adenocarcinoma.

The database included 4,892 patients with localized cancer, of whom 3,262 were treated with a prostatectomy and 1,630 who had external beam radiation therapy, brachytherapy, or cryotherapy.

All told, 1,015 patients were treated with androgen deprivation therapy, including 266 of those who had surgery and 749 of those who were treated non-surgically.

The primary endpoint of the study was the number of patients who died of cardiovascular causes, including, among other conditions, myocardial infarction, coronary artery disease, cardiac ischemia, or thromboembolic disease.

Overall, 131 patients in the study group died of cardiovascular causes during a median follow-up of 3.8 years, the researcher found.

A competing risk-regression analysis that controlled for age and cardiovascular risk factors found that:

• Androgen deprivation therapy among surgical patients was associated with an increased risk of cardiovascular death. The adjusted hazard ratio, was 2.6, with a 95% confidence interval from 1.4 to 4.7, which was significant at P=0.002.
• Among surgical patients younger than 65, the five-year cumulative incidence of death from cardiovascular causes was 3.6% for patients using androgen deprivation therapy and 1.2% for the rest.
• Among older surgical patients with and without androgen deprivation, the five-year cumulative incidence of death from cardiovascular causes was 5.5% and 2.0%, respectively.
• Among both surgical and non-surgical patients, age was associated with an increased risk. The adjusted hazard ratio in both cases was 1.07, with a 95% confidence interval from 1.02 to 1.1, which was significant at P=0.003 for the surgical group and P=0.004 for the non-surgical group.

The researchers also found that patients who used androgen deprivation therapy were more likely to have significantly higher pretreatment levels of prostate-specific antigen and biopsy Gleason scores, both at P

While those factors were accounted for in the analysis, they said, other confounding factors might have been omitted from the retrospective analysis.

Nevertheless, they said, "dismissing this hypothesis seems imprudent." The idea that patients considering the treatment should consider a careful cardiovascular evaluation and follow-up makes sense, they said.

Dr. Seidenfeld and colleagues did not report any conflicts.