Adding ADT to radiation therapy problematic for high-risk patients with history of heart disease

A new research letter just published in the Journal of the American Medical Association appears to confirm the risks associated with use of androgen deprivation therapy (ADT) for treatment of prostate cancer among men with a history of significant heart disease.

D’Amico et al. carried out an analysis of long-term follow-up data from a trial in which 206 patients with unfavorable-risk prostate cancer were randomized to receive radiation therapy with or without 6 months of neoadjuvant/adjuvant ADT as first-line treatment for their cancer. Additional information is available in this report on the HealthDay web site.

At a median follow-up of 16.62 years,

  • 156/206 patients (75.7 percent) had died.
  • Of the 156 patients who had died,
    • 29 (18.6 percent) had died of prostate cancer.
    • 39 (25.0 percent) had died of cardiac disorders.
    • 88 (56.4 percent) had died of other disorders.
  • Patients who had a history of heart problems lived longer after radiation treatment alone than similar men who were given radiation and ADT.
  • Patients who had no history of  heart problems lived longer if they were given combination therapy with radiation + ADT.

Dr. D’Amico is quoted in the HealthDay report as having clearly stated:

We found that there was no survival benefit to adding hormones to [radiation therapy for] men who had had a heart attack. In fact, they died sooner.

and he went on to state that the main cause of death was a fatal heart attack.

Now we should be very clear that:

  • This finding is not going to change standard practice, in which men who are diagnosed with high-risk prostate cancer and who elect to be treated with radiation therapy should normally be treated with 6 months of neoadjuvant/adjuvant ADT.
  • This finding does suggest strongly that men with high-risk prostate cancer and a prior history of heart disease, if treated with radiation therapy + ADT, should be carefully assessed by their cardiologist prior to initiation of treatment and appropriately monitored by their cardiologist during treatment.
  • Some high-risk patients with a history of heart disease simply may not be appropriate candidates for treatment with radiation + ADT, which then raises the question about how they should get treated and whether, in such cases, radiation without ADT may be “good enough.”

One Response

  1. Thanks as always for highlighting what has potential to be an important study affecting choices for many patients. We can probably make some good guesses as to what is behind these results.

    Having been diagnosed (late 1999) with a high-risk case during the period of the study (1995-2001), and having been on ADT as my primary and only therapy until 2013, I think I understand what is driving these results. I can empathize with these patients because, though my heart was in great shape, my overall cardiovascular health was not so great as my cholesterol was generally more than 250, despite ample aerobic exercise.

    The question is why the high-risk men who had had a heart attack were worse off on ADT than they would probably have been, per this study, if they had not had ADT to support their radiation. I’ll hypothesize that there are probably several factors at work. It is reasonable to suspect that the history of heart attack was associated with substantially higher cholesterol levels in this group than in the other group that had not had any heart attacks, and we now know that high LDL cholesterol is associated with poorer outcomes for prostate cancer patients. We also know that ADT tends to raise cholesterol and other metabolic syndrome factors unless adequate countermeasures are employed. Just 6 months of ADT seems a rather short period to my layman’s eyes for aggravating cholesterol enough to contribute to a substantial difference in survival, but ADT would also be likely to be increasing blood pressure, obesity, and perhaps diabetes for some of these men at higher cardio risk, and the combined effects of these factors, if uncountered, seem likely to further increase risk of death.

    Regarding countermeasures, we know that there are ways that work for many of us to decrease or eliminate these adverse side effects of ADT. Prominent general countermeasure categories, all with at least fair supporting evidence, are diet and nutrition, strength and aerobic exercise, stress reduction, supportive medications (such as a statin drug and metformin), and non-use of tobacco. My own diagnosis motivated me to rapidly change my diet (no red meat, even more fish, more lycopene, more green tea, vitamin D3, fish oil, pomegranate extract, etc.) and eventually take a statin drug while maintaining exercise and not smoking. However, it seems likely that many men with a history of heart attack are not used to a disciplined lifestyle that would foster adoption of these countermeasures. Various studies have indicated that the lack of such discipline is probably what got them into cardiovascular trouble.

    Therefore, while ADT can be used safely by many of us, especially for a short period supported by countermeasures, it would probably be more risky for men with a history of heart attack. As well as more intensive medical monitoring for higher-risk radiation patients on adjuvant ADT with a history of heart attack, the health care team should probably also strongly encourage and support use of appropriate countermeasures for the side effects of ADT.

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