The risk for cardiovascular events among prostate cancer patients on ADT (again)


As our regular readers will be well aware, the topic of risk for cardiovascular disease among prostate cancer patients being treated with any form of androgen deprivation therapy (ADT, also known as “hormone” therapy) comes up on a regular basis.

While no one disagrees about the fact that there is undoubtedly some degree of such risk — particularly among patients with a prior history of cardiovascular disorders — the actual degree of that risk is a topic that can stimulate strong feelings among specialists.

As far as we are aware, there has never been any evidence of any significant increase in risk for cardiovascular complications associated with ADT in the randomized, prospective clinical trials of orchiectomy or the LHRH agonists or the antiandrogens. However, it has to be understood that such clinical trials tend to enroll patients with limited risk for complications of treatment because many such patients would be ineligible for trial enrollment for any one of a number of possible factors. In the “real world” of clinical practice, the situation is inevitably rather different.

A new paper by O’Farrell et al., just published in the Journal of Oncology, provides data from what we believe to be the largest, registry-based study published to date.

O’Farrell et al. used data from the Swedish national health care registers to look at data from a cohort of 41,362 men with prostate cancer who received treatment between 2006 and 2012. They then compared those data to analogous data for 187,785 age-matched, prostate cancer-free men over the same time period. Here is a summary of the key findings:

  • 10,656/41,362 prostate cancer patients (25.8 percent) received antiandrogen therapy alone.
  • 26,959/41,362 prostate cancer patients (65.2 percent) received LHRH agonist therapy.
  • 3,747/41,362 prostate cancer patients (9.1 percent) received an orchiectomy.
  • Compared to the prostate cancer-free men, the risk for cardiovascular disease was
    • Decreased by 13 percent in the prostate cancer patients receiving antiandrogen therapy (hazard ratio [HR] = 0.87)
    • Increased by 21 percent in the prostate cancer patients receiving LHRH therapy (HR = 1.21)
    • Increased by 16 percent in the prostate cancer patients receiving an orchiectomy (HR = 1.16)
  • For men who had had two or more cardiovascular events prior to initiation of ADT, the risk for cardiovascular disease within 6 months of initiation of ADT was
    • Increased by 60 percent in the prostate cancer patients receiving antiandrogen therapy (HR = 1.60)
    • Increased by 91 percent in the prostate cancer patients receiving LHRH therapy (HR = 1.91)
    • Increased by 79 percent in the prostate cancer patients receiving an orchiectomy (HR = 1.79)

The authors conclude that:

… there should be a solid indication for ADT in men with [prostate cancer] so that benefit outweighs potential harm; this is of particular importance among men with a recent history of [cardiovascular disease].

 

3 Responses

  1. Low T has many dangers. This is only one of them!

  2. One doctor here told me that a cardiovascular event was their main worry while I was being treated with Zoladex for 3 years. Given this, it seems they were right. I suspect the reason to include ADT as adjuvant for 3 years and neoadjuvant (Zoladex + Casodex) for about 3 months (I forget), was my having all three high-risk factors for localised prostate cancer: PSA = 31, stage T2c, and Gleason 4 + 4. I think the risk was worth it, even given our lack of knowledge about what the most effective ADT periods are for high-risk patients.

  3. Could ADT with an LHRH agonist or orchiectomy be a proxy for a poorer health situation, explaining the results in part?

    In fairly recent years, especially the years from 2006 and later, it is well known that antiandrogen therapy is not as effective as a monotherapy at controlling testosterone produced by the testes by either an LHRH agonist or orchiectomy. It is a reasonable choice for some men, based on the balance of risks and benefits, but it is likely that at least a substantial majority of men on testosterone suppression had more serious cancer, which is often associated with more serious overall health factors, than the men having antiandrogen therapy alone. It would be really helpful if the researchers found a way to test this, but I suspect that would have been too daunting a task.

    Similarly, men who had had two or more cardiovascular events prior to any ADT were clearly in challenging medical shape, likely with metabolic syndrome issues, even before starting ADT. ADT is known to make metabolic syndrome issues more likely or more difficult, so the results are not surprising. My impression is that men with no metabolic syndrome issues who use appropriate side-effect countermeasures while on testosterone suppression would have a substantially lower risk than indicated in this study.

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