Hormone therapy, radiotherapy, and risk for cardiovascular mortality


An article in this week’s Journal of the American Medical Association has gained a great deal of media attention because it links hormone therapy in prostate cancer patients to a risk for death in patients with pre-existing cardiovascular disorders. The “New” Prostate Cancer InfoLink feels that it should emphasize that the outcomes reported in this study are actually not surprising at all. The risk of cardiovascular mortality associated with hormone therapy in men with prostate cancer  is well known and well understood. What is surprising to us is that these men were ever exposed to hormone therapy under the circumstances described!

The study by Nanda et al. addresses data from a cohort of 5,077 men with localized or locally advanced prostate cancer who were consecutively treated with or without a median of 4 months of neoadjuvant hormone therapy followed by radiation therapy at a suburban cancer center between 1997 and 2006, and were followed until July 1, 2008. In is highly appropriate to combine hormonal therapy with radiation therapy for treatment of patients with unfavorable-risk prostate cancer, because it has been clearly shown to increase median survival — except in certain men with moderate to severe comorbidities.

The authors state that, “it is unknown which comorbid conditions eliminate this survival benefit.” However, The “New” Prostate Cancer InfoLink would politely suggest that the adverse cardiovascular impact of hormone therapy has been well known for decades, and while the adverse cardiovascular impact of LHRH agonists is certainly not as significant as that of older estrogen-like homone therapies (e.g., diethystilbestrol), this impact is still far from negligible.

Nanda et al. were seeking to assess whether neoadjuvant hormone therapy prior to radiation therapy affects the risk of all-cause mortality in men with prostate cancer and coronary artery disease (CAD)-induced congestive heart failure (CHF) or myocardial infarction (MI) compared to patients with no comorbidity. The patients had a median age of 69.5 years.

The results of their analysis showed the following:

  • Neoadjuvant hormone therapy was not associated with an increased risk of all-cause mortality in men with either no comorbidity or a single CAD risk factor after median follow-ups of 5.0 and 4.4 years, respectively.
  • For men with a CAD-induced CHF or MI, after a median follow-up of 5.1 years, neoadjuvant hormone therapy was significantly associated with an increased risk of all-cause mortality (26.3 vs 11.2 percent, or more than double the normal risk).

The authors conclude that, “Neoadjuvant HT use is significantly associated with an increased risk of all-cause mortality among men with a history of CAD-induced CHF or MI but not among men with no comorbidity or a single CAD risk factor.”

What is surprising to The “New” Prostate Cancer InfoLink is that patients with a history of CHF or MI would have been exposed to hormone therapy in this setting except under the most exceptional circumstances. Such men are already at high risk for further cardiovascular disease. The risk of death from a heart attack even on average overall is some 10 times higher than the risk of death from prostate cancer. Why would one expose a man with an already high risk for cardiovascular mortality to a form of treatment that would only increase that risk?

For a sample of the media attention givenm to this study, see yesterday’s story in the Washington Post.

Editorial comment: The author should, under the circumstances, note that since he had a heart attack himself nearly 3 years ago, he is very conscious of the fact that any form of hormonal therapy that he might need in the future comes with a particular increase in risk for cardiovascular side effects that might not justify the theoretical benefit of the hormone therapy for another medical condition.

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