Novel Approaches in Prostate Cancer Treatment - Episode 3

Optimal ADT for Patients With Prostate Cancer and CV History


Dan George, MD: Bertrand, any other thoughts on this space with early localized disease?

Bertrand Tombal, MD, PhD: That’s a space that we urologists know very well. We’ve been giving hormones for 20 years, and there is a subgroup of patients we don’t pay enough attention to. These are the patients who had previous cardiovascular history—those who have experienced myocardial infarction, have a stent, had a stroke. I would say within 2 years there has been a whole lot of information about these patients, and several of observations have to be made. The first 1 is if you don’t take care of this properly, you can have up to 1 patient of 3 who is going to present a new cardiovascular event. It’s been confirmed with ABI [abiraterone] and ENZA [enzalutamide] as well. So you shouldn’t treat these patients the same way. From a basic science perspective, we have learned a lot that cardiomyocytes and lymphocytes in the heart do express FSH [follicle-stimulating hormone] receptor, androgen receptor, and GnRH [gonadotropin-releasing hormone receptor] receptors. There’s a whole world of exploration around the benefit of the GnRH antagonist.

In Journal of Urology, a few weeks ago there was a beautiful paper that showed if you treat patients with previous cardiovascular disease with a randomized agonist or antagonist, you get 16 times more cardiovascular event with the agonist. The fact that you see much less with the antagonist, this is probably linked to direct activation on the GnRH receptor and FSH. On top of that, it’s coming with initial information about the value of NT-proBNP [N-terminal pro B-type natriuretic peptide] as a marker—probably in a few years a point-of-care marker—to identify patients at very high risk of cardiovascular disease.

We know that the big problem with the big trial is that they incorporated very healthy patients. This is not the typical prostate cancer, so really the message is if your patient is on Plavix [clopidogrel bisulfate] or something like this, please be careful. You may actually have no benefit from the treatment because you’re going to induce the cardiovascular disease. So I believe it’s very important.

Dan George, MD: I think this is a really important theme, and 1 of the concerns we have about curing patients is that it comes at a cost. These are the costs that we do need to discuss. It brings up the point of do we need to cure patients? Are there patients for whom we can do active surveillance with early prostate cancer? What do those patients look like? What are the data supporting that?

Charles Ryan, MD: Well, I would actually counter and pick up on what Bertrand said by asking the question of how confident are we that the duration of ADT [androgen deprivation therapy], for example, that we give in response in combination with radiation, is the optimal duration for that patient? As Bertrand said, studies that pick fit patients in general have a proscribed period of time, and then we say that’s the duration that you need. It could be that patients with cardiovascular risk may benefit from a shorter duration of ADT, because that would be the sweet spot where they get the benefits of the ADT but not the risks of it. There’s a lot more work to be done. Hormone therapy is, in many ways, such a basic thing, but it’s also so complex. It gets us back to our roots in internal medicine, in fact. There are a lot more studies that need to be done.

Dan George, MD: It’s the art of medicine, isn’t it? It’s taking this clinical data, prescribed data, and putting it into the real world, in the real practice.

Charles Ryan, MD: For high-risk patients, I will sometimes think about those risks and the competing risks for the patient. What I typically will say is, for example, if the data support 2 years of ADT, I’ll say, “Well, let’s begin it, and this is what the data say.” But I would also want to renegotiate after a year, so if a patient is doing exquisitely well from a cancer-control perspective but is having adverse effects that they don’t like, then we have a conversation.

Transcript Edited for Clarity