Increased risk of death for men with heart conditions undergoing RT with hormone therapy for prostate cancer

Men with coronary artery disease-induced congestive heart failure or heart attack who receive hormone therapy before or along with radiation therapy for treatment of prostate cancer have an associated increased risk of death, according to a study in the August 26 issue of JAMA.

Patients with localized prostate cancer have several options available for treatment, including the use of brachytherapy (treatment in which radioactive seeds are implanted in the prostate), both as monotherapy and in conjunction with external beam radiation therapy, according to background information in the article. Neoadjuvant (treatment that is given before or with the primary treatment) hormonal therapy (HT) is used as a means for prostate gland cytoreduction (decrease in number of cells, as in a tumor) in order to eliminate pubic arch (an arch formed by the pubic bones) interference and improve the ability to perform brachytherapy. Previous research has suggested that "hormonal therapy when added to radiation therapy (RT) for treating unfavorable-risk prostate cancer leads to an increase in survival except possibly in men with moderate to severe comorbidity [co-existing illnesses]. However, it is unknown which comorbid conditions eliminate this survival benefit," the authors write.

Akash Nanda, M.D., Ph.D., of Brigham & Women's Hospital-Dana-Farber Cancer Institute, Boston, and colleagues assessed whether neoadjuvant HT use in men with prostate cancer treated with brachytherapy affects the risk of all-cause death of men with known coronary artery disease-induced conditions, including congestive heart failure and heart attack. The study included 5,077 men (median [midpoint] age, 69.5 years) with localized or locally advanced prostate cancer who were treated with or without a median of 4 months of neoadjuvant HT followed by RT between 1997 and 2006 and were followed up until July 2008.

During the study period, 419 men died. Of those, 200 had no underlying comorbidity, 176 had one coronary artery disease risk factor, and 43 had a history of known coronary artery disease resulting in congestive heart failure or heart attack. Analyses of the data indicated that "when considering comorbidity groups separately, neoadjuvant HT use was not associated with an increased risk of all-cause mortality in men with no comorbidity (9.6 percent vs. 6.7 percent) or a single coronary artery disease risk factor (10.7 percent vs. 7.0 percent) after median follow-ups of 5.0 years and 4.4 years, respectively," the researchers write.

However, for men with coronary artery disease-induced congestive heart failure or heart attack, after a median follow-up of 5.1 years, neoadjuvant HT use was associated with nearly twice the risk of all-cause mortality (26.3 percent vs. 11.2 percent).

"It is also important to note that the population of men in whom the use of neoadjuvant HT may be detrimental was limited to 5 percent (256 of 5,077) in this community-based study cohort. This latter point may explain why there has been a survival benefit observed in the major randomized trials comparing HT plus external beam radiation therapy to external beam radiation therapy alone," the authors write.

"The clinical significance of this finding is that for men with favorable-risk prostate cancer and a history of congestive heart failure or myocardial infarction who require neoadjuvant HT solely to eliminate pubic arch interference, alternative strategies such as active surveillance or treatment with external beam radiation therapy or prostatectomy should be considered. However, for men with unfavorable-risk prostate cancer who require HT in addition to radiation therapy to take advantage of its survival benefit, appropriate medical evaluation prior to initiation should facilitate clinicians in balancing the relative risks against the benefits of HT use."

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