Prostate Cancer: Evolving Treatment Approaches - Episode 2
Neal Shore, MD, FACS: You’ve touched on cardio-oncology, which I think is super important. We’re going to talk about that. It’s really an area that we’ve given short shrift, and there are a lot of really interesting data on it these days. But let me get back to you, William. I think this is important, some of the basic blocking and tackling. You’re going to start a therapy that is testosterone suppressive, whether it’s an agonist or antagonist and whether you get there more rapidly with 1 versus another. We’ll talk about the AE [adverse event] profiles. But tell me, in your practice, how are you monitoring testosterone levels? Do you get a baseline testosterone level? When do you check the testosterone level again?
William Oh, MD: I do get a baseline testosterone level because it’s very helpful for me to understand what’s going to happen if we’re going to stop or change therapy down the road. I do monitor it on a fairly regular basis, at least 4 times a year. You may argue that you don’t need to check it that often. Certainly, in the beginning, they’re rare but there are ADT [androgen deprivation therapy] failures: patients who get an androgen deprivation therapy and actually don’t have appropriate testosterone suppression. It gives us information that I think can be helpful in monitoring what’s really happening to their disease because PSA [prostate-specific antigen] is always going to be in relation to their testosterone levels. In fact, we know prognostically that’s also important regarding why some therapies—for example, AR [androgen receptor]—targeted therapies—may work better than chemotherapy, for example, in certain circumstances.
Neal Shore, MD, FACS: Does anybody not check a baseline testosterone level?
Nancy Ann Dawson, MD: I always get one.
Neal Shore, MD, FACS: If you check a baseline testosterone level and the patient’s at eugonadal levels, Nancy, where are you aiming? Where do you want that testosterone suppression to be?
Nancy Ann Dawson, MD: Everybody says you want it to be castrate, which is defined as less than 50 ng/dL. But most of us, at least myself, would like to see it less than 10 ng/dL or less than 5 ng/dL. The lower the better as far as I’m concerned.
Neal Shore, MD, FACS: Pedro, what do you do?
Pedro C. Barata, MD, MSc: I agree. For sure, the definition is 50 ng/dL. I use below 20 ng/dL because that’s what we expect with surgical castration. More contemporary data suggest that the lower the level is, the better. You have the analysis by quartiles. But I would like to highlight William’s point that, indeed, if you treat prostate cancer enough, you’re going to get 1, 2, or 3 patients a year where despite LHRH, for instance, he’s not well suppressed. We see a number of cPSA [complexed PSA] levels rise, and we don’t know what’s going on.
It’s just a consequence of the fact that we don’t have therapeutic levels of testosterone. In those circumstances, you can switch to a different LHRH therapy. In some cases, we can revisit the concept of surgical castration. Actually, this happened to me in the last month. I had a call specifically about that. It’s something we should talk about. We do expect efficacy above 90% of the time, but I think the literature refers to 4% to 10% of patients where the therapeutic levels of testosterone are not achieved.
Neal Shore, MD, FACS: Right. Maybe there’s a mutational event in the anterior pituitary. Maybe it’s a metastatic tumor making extra testosterone. Maybe it’s an adrenal source. Will you switch an agonist to an agonist or will you go agonist to antagonist or antagonist to agonist, bilateral orchiectomy, or all combinations?
Pedro C. Barata, MD, MSc: That’s a great question. I don’t think we have level 1 data to answer that question definitively. I usually pick another agonist just because it’s more convenient. The antagonist options, so far, are every month. I often do it every 4 or 6 months in clinic. I do have that discussion. As Alicia mentioned, if I have a patient with cardiovascular events in the first place, I’m going to have a low threshold to offer him an antagonist. That trial is going to soon answer that question about cardiovascular safety comparing agonists with antagonists. But yes, it’s a dealer’s choice. Most patients, I would argue, are not open to get surgical castration. I would argue that our discussion is oftentimes about agonist versus antagonist and how often are we going to do the shot.
Transcript Edited for Clarity