Androgen deprivation therapy: overused and misunderstood?

There is an increasing belief among at least some opinion-leaders in the prostate cancer treatment community that androgen deprivation therapy has been and still is being significantly overused. The most recent expression of this opinion comes in an article today on the Medscape web site.

In the 1990s there was an all-out attempt by various pharmaceutical companies to maximize the use of the LHRH agonists and the antiandrogens in the USA and elsewhere. Certainly, at that time, these therapies were a great deal easier to accept than surgical orchiectomy or the perceived and real cardiovascular risks associated with diethystilbestrol (DES), but marketing became very aggressive. Commercialization strategies in the USA allowed for physician practices to purchase LHRH agonists at costs that were lower than the amount of money that Medicare reimbursed for use of these products, and so physicians made a not insignificant profit on each dose of the LHRH agonists that they administered to patients in their offices.

That form of financial incentive to prescribe and administer LHRH agonist therapy has now been almost completely take off the table, but the mindsets of many physicians and patients still reflect an attitude that says one just needs to “do something” when the PSA is rising, despite the fact that “doing something” may not be supported by the literature and (in the case of hormone therapy) has the potential for at least as much harm as good in many, many patients.

Speaking at the Genitourinary Oncology Symposium earlier this year, several opinion-leaders made the point that the early use of hormone therapy was not necessarily in the best interests of patients because of the risks for a wide variety of side effects — from cardiovascular disease to metabolic syndrome and mental health issues. Today’s Medscape article also focuses on a number of the same points — although they are being made by different experts.

The “New” Prostate Cancer InfoLink has long taken the position that, for many patients with relatively low risk disease, early therapy in general may not be in the best long-term interests of the patient, based on the data currently available — and this is as true of the use of hormone therapy as it is for surgery or radiation as first line therapy in older patients with low risk disease. However, we also appreciate how hard it is for many people diagnosed with cancer to understand that they are likely to have relatively indolent disease, and that the currently available forms of treatment, when implemented early, may leave the patient with serious quality of life issues.

Obviously every individual patient has to make his own decision about his therapy in close collaboration with his physicians. The “New” Prostate Cancer InfoLink would simply ask patients and their physicians to remember a relatively short list of facts when thinking about the timing of hormone therapy:

  • For patients with low risk disease and a very long PSA doubling time (> 15 months), there appears to be no good reason to initiate hormone therapy any earlier than one absolutely has to. Such patients will almost invariably get all of the available benefit of hormone therapy even if it is delayed until very late in the disease process, and in the meantime they will suffer none of the adverse effects of long-term ADT.
  • For patients with intermediate and high risk disease, and particularly those with a very short PSA doubling time of < 3 months, early initiation of hormone therapy is probably essential because of high risk for rapid disease progression.
  • For patients with intermediate and high risk disease and a moderate PSA doubling time (of between 3 and 12 months) the timing and form of hormone therapy needs to be carefully discussed between the doctor and the patient. The primary goal should be to control the risk for disease progression using a treatment regimen that also minimizes the potential side effects of hormone therapy. One way to do this is to treat the patient not just every month or every 3 months but perhaps based on his PSA level and his testosterone level at any specific point in time. Another is through the use of “traditional” intermittent hormone therapy.

For men who may have to live with a possible need for hormonal ablation over a decade or more, there are a lot of potential risks associated with such therapy — from the irritation of hot flashes and the loss of one’s libido to osteoporesis, fractures, weight gain, metabolic syndrome, cardiovascular disease, and “hormone brain.” We need to be treating the whole man, not just his PSA level, however hard that may seem to be.

One Response

  1. This article and analysis are a breath of fresh air on a subject urologists have dominated for too long. Bless their hearts, urologists want to stop the cancer from progressing, but they are apparently way out of their league in assessing the myriad of side effects of hormonal ablation. What do they know about bones? About hearts? About the effects all of this can have on a patient’s (and/or a patient’s significant other’s) mind?

    The use of hormonal ablation really should be something a team of physicians of the different relevant specialties manage together in consultation with the patient. That would move this therapy from the Dark Ages into the modern world where patients’ overall well-being is supposed to matter.

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