'Reassuring': ADT for Prostate Cancer Does Not Up CV Death

Nick Mulcahy

October 05, 2011

October 5, 2011 (Miami Beach, Florida) — Androgen-deprivation therapy (ADT) is an effective treatment for men with "unfavorable-risk" prostate cancer, and it does not increase the risk for cardiovascular (CV) death, concludes a new study. These results contradict earlier suggestions that this risk might be increased.

The new findings come from a meta-analysis, the first on ADT and CV-related mortality, presented here at the American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting.

This "should be reassuring for the vast majority of men who have received ADT or are considering it," said lead author Paul Nguyen, MD, from Dana-Farber/Brigham and Women's Cancer Center in Boston, Massachusetts.

The study has an important caveat: the findings could differ in men with congestive heart failure or who have had a myocardial infarction.

Still, even with the study's limitations, these data offer a counterpoint to retrospective studies that found a higher risk for CV mortality among men receiving ADT for prostate cancer, explained Dr. Nguyen.

Those studies, plus data indicating an association between ADT and an increased risk for CV complications, led to a consensus statement last year from the American Heart Association, the American Cancer Society and the American Urological Society.

The statement, which was endorsed by ASTRO, asserted that "there may be a relation between ADT and cardiovascular events and death."

Subsequently, in October 2010, the US Food and Drug Administration called for new labeling on gonadotropin-releasing hormone (GnRH) agonists. The black-box warning now states that the agents "increase risk of diabetes and certain cardiovascular diseases (heart attack, sudden cardiac death, stroke)."

Improve Analysis of the Problem

In an interview with Medscape Medical News, Dr. Nguyen described the consensus statement as "everybody lining up against androgen-deprivation therapy."

He and a group of colleagues sought to improve the power of the statistical analysis of the problem.

They performed a literature review of randomized trials in prostate cancer that compared GnRH-agonist-based ADT with no ADT and that reported CV-related deaths. They found 8 studies that met their inclusion criteria, comprising a total of 4141 patients, all of whom had intermediate-risk prostate cancer or higher (but no metastatic or hormone-refractory disease). In 5 of the studies, the local therapy patients received was radiation; in the other 3 studies, patients underwent surgery or received no local therapy.

The risk for CV death was similar in the ADT and no-ADT groups (11.0% vs 11.2%). The relative risk for CV death for ADT, compared with no ADT, was 0.93 (95% confidence interval, 0.79 to 1.10; P = .41).

The results were similar in all the subgroups the investigators examined, said Dr. Nguyen, including the subgroups of short-course ADT (6 months or less), long-course ADT (3 years or more), men older than 70 years, and radiation use.

The meta-analysis provides additional reassuring news: ADT improves outcomes. Specifically, compared with no ADT, ADT reduced prostate-cancer-specific mortality (relative risk [RR], 0.68; P < .001) and all-cause mortality (RR, 0.88; P = .005).

Men With Preexisting CV Disease

This is a "great paper" that "employs modern epidemiologic methodology to seek out differences that would not have been seen in smaller studies," Phillip Devlin, MD, secretary/treasurer of ASTRO, told Medscape Medical News. Dr. Devlin is also from Dana-Farber/Brigham and Women's Cancer Center, and acknowledged that he is not a completely impartial commentator, as he is Dr. Nguyen's boss.

Dr. Devlin believes that patients will be calmed by these results, which provide a "sense of greater comfort" and allow clinicians to say that "there may be less risk than we thought" with ADT and cardiac death.

Nevertheless, clinicians should provide careful monitoring of patients on ADT for CV disease, said Dr. Devlin.

The study did not examine whether ADT is associated with a reduction in CV events such as congestive heart failure and myocardial infarction.

Retrospective data suggest that ADT harms men with preexisting CV disease, said Dr. Nguyen.

The extent of the harm is unclear, he reported. For instance, a 2009 study indicated that only 5% of men with a history of congestive heart failure and myocardial infarction were harmed by ADT, as reported by Medscape Medical News.

Dr. Nguyen is also the author of a study that found that men with high-risk prostate cancer have an increased risk for death with ADT if they have a history of congestive heart failure and myocardial infarction (RR, 2.6; P = .01).

Dr. Nguyen reports receiving research funding from Varian. Dr. Devlin has disclosed no relevant financial relationships.

American Society for Radiation Oncology (ASTRO) 53rd Annual Meeting: Abstract 11. Presented October 3, 2011.

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