Intermittent vs. continuous androgen deprivation therapy — expert comment


A new article offers expert perspective on the relative merits of intermittent and continuous androgen deprivation therapy (ADT) in the treatment of men with metastatic prostate cancer or recurrence of disease following first- or second-line treatment.

On pages 13-14 of the May issue of AUA News, Spendlove and Crawford put forward a strong argument that intermittent ADT has now demonstrated that it is no less effective than continuous ADT and that it clearly reduces the impact of the side effects of hormone therapy on patient quality of life.

They note that the available data do need to be confirmed by data from other large ongoing trials. But interestingly they also make the point that effective ADT of any type should reduce the serum testosterone level to < 20 ng/dl (which has long been a controversial issue).

Perhaps most importantly, the authors lay out a series of five principles that they believe should be adopted in the widespread application of intermittent ADT, as follows:

  • The initial induction phase of hormone therapy should last at least 6 to 9 months.
  • The initial induction phase should only be stopped if there is a clear impact on patients’ PSA levels.
    • For men with metastatic disease the PSA should fall to < 4.0 ng/ml.
    • For men with recurrent disease the PSA should fall to < 0.5 ng/ml.
  • Treatment should be re-started if
    • There is clear clinical progression of disease.
    • PSA values rise to 10 or 20 ng/ml in men with metastatic disease.
    • PSA values rise to 4.0 ng/ml in men with non-metastatic disease.
  • When treatment is re-started, it should be continued for up to 6 to 9 months.
  • Appropriate examinations and PSA tests should be conducted on all patients every 3 or 6 months.

The authors acknowledge that their recommendations about specific PSA levels for stopping and re-starting intermittent ADT are controversial.

The advocates for intermittent ADT based on the use of ADT3 (the combination of an LHRH agonist, an antiandrogen, and a 5α-reductase inhibitor) will obviously consider “standard” intermittent ADT to be suboptimal. This may or may not be the case, but we have no level 1 data from randomized clinical trials to substantiate the benefits of intermittent ADT3.

It is worth noting a statement by the authors (in a publication aimed primarily at their colleagues in the urology community) that, “Today, much of the credit for IADT can be given to patients.” Maybe if the patient advocates for IADT3 all start shouting a little louder, they can persuade Dr. Crawford and his colleagues to implement a randomized clinical trial of standard IADT vs. IADT3.

We should conclude by noting that intermittent ADT is not going to be effective for all patients, that intermittent ADT may have less value for the men who have only low levels of adverse effects to ADT, and that it would be helpful if we were able to predict which patients were more likely to respond well to IADT before implementation. Spendlove and Crawford make it clear, however, that they believe it is now appropriate to have a careful discussion will every patient who is faced with the need for ADT about the risks and benefits of intermittent and of continuous ADT so that patients are fully aware of their options.

One Response

  1. Timely article — I have been working with a couple of guys whose doctors have recommended intial 2-year-long ADT in response to metastatic disease. For one guy it is recurrent, and so far known to be in the prostate bed; for the other, he was diagnosed with metastatic disease with multiple bone spots and positive lymph nodes.

    I was surprised to hear very reputable doctors recommend 2 years of initial ADT — although neither were med/oncs! I have forwarded the article to one of the docs; I don’t know the other well enough but will get a message to him.

    rd

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