IADT — pro and con; a follow-up

The other day we mentioned two articles in a recent issue of JAMA Oncology that dealt with the role of intermittent androgen deprivation therapy (IADT) in the management of progressive prostate cancer today. We have now had the good fortune to be able to read both of the two articles in full, thanks to a kind correspondent.

As a reminder, these were the two articles:

Having had the chance to review both of the articles in full, the distinction between the positions of the two pairs of authors is actually much as we had expected it to be.

Hussain and Eisenberger argue that after years of research there is no good data from randomized clinical trials to suggest that there is any significant and unarguable benefit from IADT compared to continuous ADT in terms of either survival or demonstrable quality of life on average across hundreds if not thousands of patients. And this is true. On the other hand, there are very real questions about whether any of the trials that have ever been carried out were designed and implemented in ways that would have been likely to show such benefits in the patients most likely to gain such benefits.

Conversely, Klotz and Higano take the position that there are clearly patients who appear to gain great benefits from IADT, if only in terms of quality of life, and that the trick is to be able to identify such patients, let them make the decision about how they want to be treated after explaining the possible options, and then monitor them with care over time while employing to one’s best ability the type of therapy that the patient has elected (i.e., continuous or intermittent ADT). In their article, Klotz and Higano offer a very reasonable algorithm for the identification and selection of those men with progressive prostate cancer who may be the best candidates for IADT.

To some extent, as he suggested earlier, your sitemaster sees this pro/con discussion as being inappropriate. A key reason for this is that he is aware that both of the physicians who argue that there is no place for IADT today have (at least until recently) been willing to administer IADT to patients who argued that this was what they wanted to do — despite the two physicians reservations and beliefs that there was no benefit and some additional risk to IADT.

So the question we really need to be asking is not whether IADT is appropriate or not, in general, for all men with progressive prostate cancer. Rather, the question is whether it is appropriate to inform at least some of one’s patients that IADT is an option with no categorically proven benefit for all patients but apparent benefits in some patients, and then help the patients to make an appropriate choice that works for them. High quality patient care (as opposed to academically rigorous, evidence-based medicine) would certainly favor the second approach.

There is an important place for academically rigorous, evidence-based medicine, but …

Your sitemaster would take the position that appropriate, large-scale, randomized trials have never been carried out that could reasonably have been expected to provide an evidence-based answer to whether there was or was not a well-defined group of patients that might really benefit from IADT as compared to continuous ADT, and we have addressed that issue on more than one occasion in the past.

Editorial note: Our thanks to the kind, anonymous correspondent (who is both an oncologist and a patient) who provided the full texts of the two articles above-mentioned. We appreciate his assistance.

6 Responses

  1. If a patient takes the position that he values quality of life (defined as no unbearable side effects from treatment) over quantity of life, it’s hard for me to understand why IADT would not be preferable if in fact that patient suffers intolerable side effects while on ADT.

  2. I have discussed my case on this site before, but I have some comments about this particular topic.

    I had a metastasis to bone 9 months after brachytherapy. That was August of 2013. My urologist told me I was now incurable and said lifelong ADT was the only option. A second opinion at MD Anderson suggested a 6 month course of ADT followed by radiation to the bone metastasis. I chose that. I did not tolerate the ADT well. I had 20+ total body sweats daily, increased belly fat due to metabolic changes despite my continued fitness routine, and total and profound ED. The only thing that kept me going was the knowledge that I would get a break from the ADT at the end of the 6 months and the radiation therapy.

    My deal with my oncologist was that I would do another 6 months of ADT if my PSA rose again to 1 ng/ml. Fortunately, 3 years later, my PSA is undetectable and I have completely recovered from the ADT symptoms, including the ED. But should the need arise in the future, I know I could do another short course of ADT. Obviously my cancer responded well to the ADT and intermittent ADT is not for everyone. But if a break is possible from continuous ADT I think it should at least be discussed with the doctors.

  3. Even though I was tolerating ADT relatively well for 11 months, I went on a 7-month drug holiday and completely reversed all ADT side effects of the previous 11 months. As a Gleason 9, yes, my PSA rose quite a bit in those 7 months, so I went back on therapy, but for those 7 months I felt like a man without cancer, and I am now looking forward to my next drug holiday. No regrets. IADT is a great option for guys like me. Maha needs to walk a mile in our shoes, much as I do respect her.

  4. I second the responses of Bob and especially Len. When I started on ADT for my Gleason 9 = 5 + 4 disease, the side effects made my life close to unlivable. I had such severe drops in cognition, mood, and will that I was unable to function. A psychiatrist recommended electroshock treatment for my depression. Instead, I took a holiday from ADT and found myself back to almost-psychologically-normal-for-me within 8 months.

    Although the strength of my reaction was unusually strong, my story is not all that rare.

    Accordingly, I wonder what methodology was used to judge that, “on average”, IADT vs CADT conferred no unarguable benefit in terms of demonstrable quality of life. In particular, I wonder if the men who committed suicide were included in the average of the data sets. If they were not, then the conclusion is completely invalid.

  5. I agree that we need more trial data. As we continue to develop and explore more biomarkers at the molecular level, we may be better to define who should be on IADT versus continuous. I again suspect that some will benefit from one approach but not the other.

    I get the privilege to watch this discussion regularly with ties to all four oncologists. And others as well. Some of the points raised:

    1. Is IADT with continued relapses truly a significant improvement in quality of life?

    2. Are there significant differences in quality of life for men on continuous ADT versus orchiectomy?

    3. What would be the best approach when IADT has failed more than once in a short time and the risks are high?

    These are just some of the questions they raise. And recently, with a lot of discussion on bipolar approaches to ADT (BAT), how will that affect these approaches? Remember that if a man elects to have an orchiectomy, you can still supplement with testosterone replacement therapy under this theory.

    A lot of unanswered questions and a lot of hypotheses. And no clear direction where to go from here.

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