Androgen-Deprivation Therapy Linked To Worse Fitness, Cv Mortality

Long-term androgen-deprivation therapy (ADT) is associated with worse cardiorespiratory fitness (CRF) and higher cardiovascular (CV) mortality in prostate cancer (PC) patients with high CV risk at baseline, new research shows.

"Reduced CRF may in part mediate the increased CV risk that we observed and may represent a therapeutic target. The potential merit of exercise interventions concurrent with prolonged ADT prescription in patients with PC and high CV risk warrants investigation," Dr. John D. Groarke of Brigham and Women's Hospital in Boston and colleagues conclude in their report in JACC: CardioOncology.

ADT plus radiation therapy is often used as an alternative to surgical treatment of PC, and the intensity and duration of treatment has grown in recent years as longer-term therapy is associated with better outcomes, Dr. Groarke and colleagues note. Studies of ADT and CV disease and mortality have had mixed results, they add, with some using age-matched healthy controls rather than PC patients not receiving ADT.

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The researchers looked at 616 patients who underwent exercise treadmill testing a median of about five years after being diagnosed with PC. About a quarter had received ADT, including 99 who had ADT for six months or less and 51 who had longer-term therapy. Just over 80% had two or more CV risk factors.

Reduced CRF (eight metabolic equivalents, or METs, or less) was identified in 49% of ADT-exposed PC patients and 33% of non-exposed PC patients. Twenty-eight patients died due to CV causes, including 17 in the non-ADT group and 11 in the ADT-exposed group.

Long-term ADT was associated with significantly increased risks of poor CRF (odds ratio, 2.71) and CV mortality (hazard ratio, 3.87). The association between short-term ADT and reduced CRF fell just short of statistical significance (OR, 1.71, P=0.052), whereas there was no evidence for a link to CV mortality (HR, 1.60; P=0.420).

Overall, reduced CRF was associated with a nearly five-fold increase in mortality risk (HR, 4.60; P<0.001).

"This builds upon some of the existing literature that's already out there about the association between AD exposure and adverse cardiovascular outcomes, and I think it complements that literature because we know that many of the adverse metabolic consequences and adverse cardiac consequences can be cumulative in nature," Dr. Vivek Narayan of the University of Pennsylvania in Philadelphia told Reuters Health by phone. Dr. Narayan co-authored an editorial accompanying the study.

While it makes sense that longer-duration ADT would carry greater risk, "I personally don't think that this absolves shorter durations of androgen-deprivation therapy from adverse cardiovascular consequences," he added.

Instead of cutting back on ADT, Dr. Narayan said, clinicians should actively manage patients' CV risk, while being aware of the increased risk associated with this type of treatment.

Dr. Groarke was not available for an interview by press time.

—Anne Harding

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