ADT might increase cardiac mortality in prostate cancer patients

May 1, 2007

Androgen deprivation therapy's documented adverse effects on cardiac risk factors might translate into an increased risk of cardiac mortality for older prostate cancer patients.

Key Points

Orlando, FL-Androgen deprivation therapy's documented adverse effects on cardiac risk factors might translate into an increased risk of cardiac mortality for older prostate cancer patients, according to retrospective review of a large prostate cancer database.

Patients 65 years of age and older had a small but statistically significant increase in cardiac mortality when treated with ADT compared to prostate cancer patients of the same age who did not receive hormone therapy. The increased mortality risk did not extend to men younger than 65.

"This really speaks to the importance of a thorough cardiovascular evaluation in men who are being considered for hormone therapy," said Henry Tsai, MD, a radiation oncology fellow at Brigham and Women's Hospital and Harvard Medical School in Boston. "In patients who are being treated with hormone therapy, it may be important to monitor them for an increased risk of cardiac death."

Investigators reviewed data on 3,636 men with localized prostate cancer included in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients had been treated by surgery, external beam radiation therapy, brachytherapy, or cryotherapy with or without ADT. ADT use and duration was determined by the treating physician.

The study population had a median age of 64 years and a median follow-up of 4 years. Dr. Tsai said 735 men had received ADT for a median duration of 4.1 months. Examination of cardiac risk factors revealed heart disease in 25% of patients with ADT and 17% of those without; diabetes in 13% of the ADT group and 8% of the patients who did not receive hormonal therapy; and hypertension in 47% of patients with ADT and 41% of those without. About three-fourths of patients in both groups had a body mass index ≥25, and 10% to 11% of the men had a positive smoking history.

Men treated with ADT had an estimated 5-year cardiac mortality of 2.5%, which was significantly greater than the 0.6% rate seen in men who did not receive ADT (p<.001). When the mortality estimates were stratified by age, ADT had no impact on cardiac mortality in men <65 years (1.1% vs. 0.3% without ADT). However, older men treated with ADT had a 5-year estimated cardiac mortality of 3% compared to 0.9% in older men without ADT (p=.004).

In regression analysis, duration of ADT was a significant predictor of cardiac mortality in unadjusted (p<.001) and adjusted (p=.01) calculations. Older age also predicted an increased risk of cardiac mortality in the unadjusted (p=.001) and adjusted (p=.04) analyses. Heart disease, diabetes, hypertension, BMI, and smoking status did not predict cardiac mortality risk after adjustment for competing risks.

Dr. Tsai urged a cautious interpretation of the findings.

"We could not control for all potential cardiovascular disease risk factors and medications, notably hypercholesterolemia," he said. "There was no assessment of changes in serum testosterone levels. This retrospective study confirms an association, but not causality. Further prospective evaluation must be done to confirm these findings."