ADT and cardiovascular side effects — redux

A few days ago we commented briefly on a paper by Haque et al. on the risk for cardiovascular complications and side effects of ADT in men initially diagnosed with localized prostate cancer and supposedly managed, initially, on active surveillance.

In discussing the paper initially, we noted that it was hard to know what to make of this paper based exclusively on the abstract. We have now had the chance to read the entire paper, and it has clarified a number of issues for us.

First and foremost, the 7,637 men included in this cohort study were not, in fact, being initially managed on active surveillance at all. It is clear from the paper that they were, initially, simply being “managed conservatively”, which could have included anything from a highly structured active surveillance protocol at one end to the much simpler “watchful waiting” based on PSA levels and symptoms at the other.

Second, as we had expected, there was, in fact, no standard rationale for when ADT was started in these patients. All we know is that it got started at some point either as a first-line therapy or as a later form of salvage treatment, and that ADT comprised an LHRH receptor agonist (Lupron or similar) with or without an antiandrogen (Casodex or similar). (LHRH receptor antagonists like Firmagon were not available on the Kaiser Permanente formularies at the time of the treatment of these patients.) In other words, for at least some of these patients, ADT was not in fact given as a first-line form of therapy at all, but potentially as a form of salvage treatment or perhaps even in combination with radiation therapy. There is also no clear indication about how long patients were on ADT or whether it was continuous or intermittent.

Third, as we had suspected, the numbers of patients who actually had cardiac arrest were very small: 19/4,567 men who were not given ADT (0.42 percent) and 39/2,170 men who were given ADT (1.80 percent).

Fourth, and very importantly, there were some extraordinarily clear differences between the men who were treated with ADT and those who were not.

The 2,170 men in the ADT group are stated by the authors to have been:

  • Older, with 80.2 percent of these men being ≥ 65 years as compared to 62.1 percent of those who did not get ADT
  • More likely to have co-morbid conditions, including hypertension and diabetes, 1 year before their prostate cancer diagnosis
  • At slightly higher risk for pre-existing cardiovascular disease (22.5 as opposed to 21. 5 percent)
  • More likely to
    • Be diagnosed in 2006 or earlier
    • Have higher Gleason scores at diagnosis
    • Have a more advanced tumor state at diagnosis
    • Have a baseline PSA level > 10 ng/ml at diagnosis
  • More likely to be receiving medications for treatment of diabetes or cardiovascular conditions

Without wishing to be overly critical, these fact would appear to your sitemaster to have enormous relevance to the idea that ADT was the cause of more cardiac arrests or more cardiovascular disease in these patients.

While it is certainly true that ADT does come with cardiovascular risk factors, these risk factors are inevitably going to be higher among men who are older, have co-morbid conditions like hypertension and diabetes, are receiving treatment for pre-existing diabetes and cardiovascular disorders, etc.

As a report on the use of ADT in patients with prostate cancer in “the real world” between 1998 and 2008, this paper is actually fascinating. Contrariwise, as a paper concluding in  its abstract that,

In men with clinically localized prostate cancer who were initially under active surveillance, ADT was associated with a greater risk of heart failure in men without any preexisting CVD

the abstract of this paper appears to be highly misleading and, arguably, factually inaccurate.

Last but not least, the study conclusion includes the following statement:

… emerging evidence exists that recommending diet and exercise to patients receiving ADT for prostate cancer treatment benefits the cardiometabolic profile …; such efforts may indirectly help lower the risk of non-fatal [cardiovascular disease] in men with localised prostate cancer treated with ADT.

Really! Emerging evidence? Recommendations about diet and exercise have been being made to  men on ADT by specialists for much of the past 20+ years!

One Response

  1. In the words of that great pundit, Ali G, Sitemaster … RESPECT!!!!

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