Prostate Cancer: Evolving Treatment Approaches - Episode 1

Ep. 1: Initiating Therapy for CSPC


Neal Shore, MD, FACS: 2020 begins another exciting year in the field of genitourinary oncology, including prostate cancer, where we’ve made significant progress with several recent FDA approvals.

I am joined by a panel of my colleagues, all experts in treating advanced prostate cancer. Today we are going to highlight recent clinical data and discuss practical implications for patient care.

I am Dr Neal Shore, medical director for the Carolina Urologic Research Center in Myrtle Beach, South Carolina. Today I am proudly joined by Dr Pedro Barata, an assistant professor of medicine in the Department of Medicine, Section of Hematology and Medical Oncology at Tulane University in New Orleans, Louisiana; Dr Nancy Dawson, a professor of medicine and the director of the Genitourinary Medical Oncology Program, Georgetown Lombardi Comprehensive Cancer Center in Washington, DC; Dr Alicia Morgans, an associate professor of medicine at Northwestern University Feinberg School of Medicine; and Dr William Oh, a professor of medicine and the chief of the Division of Hematology and Medical Oncology at Mount Sinai Health System in New York, New York.

Everyone, thank you for joining us. Let’s begin. We’re going to go through 3 different areas that we are all familiar with, but it’s really changed how we think about managing patients. We’ve had a lot of breakthroughs, and with these breakthroughs we also have a lot of questions. It’s not really clear right now how we can move forward because we sometimes lack level 1 evidence. Trials are coming. More evidence and presentations are forthcoming at our major meetings. It’s been a really exciting time in the world of treating prostate cancer, particularly advanced prostate cancer, with great breakthroughs. I think this should be a great discussion.

We’ll kick it off in the first segment by talking about metastatic castration-sensitive prostate cancer [mCSPC], or what some will call metastatic hormone-sensitive prostate cancer. Let’s begin. First, William, if I can ask you to begin. ADT [androgen deprivation therapy] has been the cornerstone, the mainstay, the foundation of advanced prostate cancer since Charles Huggins and Clarence Hodges in 1941. Now that we have all these couplet therapies, talk to us a little about the timing of couplet therapy or additional therapies with traditional monotherapy ADT. Then maybe we’ll all talk about the notion of testosterone levels and when to check them, etc.

William Oh, MD: Thank you, Neal. Thanks for having me on this panel. The main essence of treatment is to deprive the cancers of testosterone. And that, as you said, has been known for 70 years. As soon as a patient presents with metastatic disease, if they’re symptomatic or asymptomatic, they should be started on ADT right away. Studies have looked at some lead-in period to start a second treatment, and there’s no optimal time, but usually in my practice I’m going to try to get a second treatment in as soon as possible, whether that’s chemotherapy or novel AR [androgen receptor]—targeted therapy. But because we’re sometimes dealing with pain and with other adverse effects, I don’t think it’s mandatory that you have to start additional therapy in the first visit. You really have to have time to get these drugs for these patients. There’s a process involved, and you want to be able to follow these patients on close follow-up. I think within the first few months of starting ADT, you generally want to make a decision about and probably start 1 of these novel therapies.

Neal Shore, MD, FACS: That’s a great point. Oftentimes, it’s challenging if you start 2 things at the same time. How do you discern tolerability and patient responses? Nancy, do you have any concerns about starting couplet therapy as opposed to monotherapy? How do you conduct dialogue with patients about that?

Nancy Ann Dawson, MD: Quite honestly, the first time I see a patient and we’re just starting therapy, after we’ve had a long discussion, they’re a little overwhelmed. I have a tendency to go ahead and say, “Well, we’re going to start you on some oral bicalutamide as we always did, and then you’re going to come back and get your first hormone shot. Then when I see you in follow-up at a month out, we’re going to talk about adding a second therapy.” I usually try to do it in stages because patients seem a little overwhelmed when I say, “All right, we’re going to start this, this, and this.” But actually, if you wanted to start a drug like enzalutamide or apalutamide, you could start it instead of the bicalutamide and do it all at once.

Neal Shore, MD, FACS: That’s an interesting point. There’s a practicality to getting it approved, preauthorization, and having it come to the patient’s accessibility. Pedro, what about you? Are you using bicalutamide?

Pedro C. Barata, MD, MSc: That’s a great question. When I have a patient with metastatic castration-naïve prostate cancer, I still use it, and I use it because the patient has disease and I worry about testosterone flare. For the most part, I use LHRH agonists and antagonists. With the agonists, we do expect testosterone flare because I don’t start them on anti-androgen on day 1, because oftentimes we need their insurance provider to approve it, etc. I try to break it into 2 or 3 visits. What I end up doing is starting the patient up front on bicalutamide and then giving him LHRH therapy a few days later, a week later or so. Then when the patient comes back to see me again—and we’re going to talk a little more about treatment intensification—that’s when I actually do the switch and swap them from bicalutamide to whatever novel agent I’m going to pick for that patient.

Neal Shore, MD, FACS: Let me ask you this question because for the longest time, we only had LHRH agonists, right? And then in 2009, we got the first antagonist. Now we’re talking about patients who have mCSPC. They have metastatic disease, whether it’s low volume or high volume. Alicia, do you have any preference about agonists versus antagonist? If you use an antagonist, do you use bicalutamide with that?

Alicia K. Morgans, MD, MPH: That’s a great question. I actually usually use the agonists, and that’s just because we traditionally have always used them. I don’t necessarily see for most patients that there’s a huge difference. Although with the agonists, we can give a depot for 3 months or sometimes 4 months. There are even formulations you can use for 6 or 12 months. Having that flexibility for patients, so that they are not tied to the clinic every month, is valuable for them.

There are some patients with very high-risk cardiovascular disease who have asked me specifically about the antagonists. I actually work with the cardio-oncologists at our institution, and we tend to use the antagonists in those situations for these very high-risk patients. I would say that the prospective data are not entirely there for that approach. But there’s enough of a signal that there’s potential benefit, and we certainly do that for those very high-risk patients.

You could actually start bicalutamide on the same day as your agonist, which we often do if we already have authorization for whatever agonist we need. We can start the bicalutamide and the agonist and do all that on the same day just to cover the flare. But the antagonist doesn’t have a flare because of the way it’s formulated and the way it works. It’s an antagonist, so there’s not going to be that stimulation of testosterone, so we do not use bicalutamide in that setting.

Transcript Edited for Clarity