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Combination Therapy for Localized Prostate Cancer

Panelists: Dan George, MD, Duke Cancer Center; Joe M. O'Sullivan, MD, FRCPI, FFRRSCI, FRCR, Queens University Belfast ; Charles Ryan, MD, Masonic Cancer Center; Christopher Sweeney, MBBS, Dana-Farber Cancer Institute; Bertrand Tombal, MD, PhD, Cliniques Universitaires Saint-Luc
Published: Friday, Oct 25, 2019



Transcript: 

Dan George, MD: Joe, if I could turn to you a little on this subject, because from a radiation standpoint, we’re really coupling 2 therapies: hormonal therapy and radiation therapy. A lot of people have focused on the local therapy. They tend to put this aside. Maybe for a lot of these issues I think, “Well, the primary care doctor will deal with it.” You heard what Chuck said. How do you incorporate that into your practice when you’re combining therapies?

Joe M. O’Sullivan, MD, FRCPI, FFRRSCI, FRCR: First, for our patients with higher-risk locally advanced disease, I think the evidence is extremely strong now that the combination of radiation and some form of androgen deprivation improves outcome. There’s no question about that. When I talk to a patient who’s at a slightly higher risk, whether it’s because of T3 disease or at least an 8 or above, I tell the patient that radiation on its own is not going to be enough. I describe different types of hormone therapy. Like Chuck, I also describe the lifestyle changes that are required to deal with that.

But I also sometimes consider using noncastration hormone therapy. For example, in Europe, we can use bicalutamide, 150 mg per day. It’s very effective, and it reduces some of the metabolic effect that you get with castration therapy. But I think it’s very important that patients understand the reasoning behind the hormone therapy. It’s to basically improve the results of local therapy. We know that hormone therapy dramatically improves it. We’ve seen this over many different trials, that the addition of hormone therapy to radiation, and the addition of radiation to hormone therapy dramatically improves survival. In fact, it’s probably 1 of the most dramatic randomized trial evidence of improved survival in prostate cancer that we have. I think the combination of hormones and radiation are 1 of the biggest reasons why we’re seeing a reduction in prostate cancer mortality overall.

Dan George, MD: Fair enough. Very good. Chris, when you’re dealing with hormonal therapy and radiation therapy, and you’re having a patient who’s struggling a little with these adverse effects, how does that factor in to how you manage it? Does it change the length of therapy you’re going to give this patient? Does it change the agents you’re using, as Joe said, or things like that? Any monitoring, like how Chuck talked about exercise? What are some of the things you counsel patients around what you can do to manage some of those issues?

Christopher Sweeney, MBBS: I’ll pick up on 1 thing and say this conversation may well actually also extend to the surgical setting if the neoadjuvant studies pan out. This conversation would be even more relevant as we intensify the hormonal therapy. So I just want to say this is not going to go away, it’s going to get more relevant, and underscore that. What I do is, I counsel patients on the adverse effects and I say, “This is what may happen, and whether we can get you through the whole period depends on how you tolerate this.” I set the expectation, “This is what we’d like to do, but if we get to a point where we’re increasing your comorbidities—which may outweigh the treatment benefit—we may have to adapt, improvise, overcome like the CIA [Central Intelligence Agency]. We have to realize that we have to individualize.

One other thing that I’m actually very clear about, what I’ve learned is that sexuality is also a major issue, and I monitor their emotional well-being. I have this great analogy from a patient of mine who shared this with me, and this is going to be a bit of a silly story, but it is very emphatic, and my patients understand it. “Chris, I’m a psychologist. You’ve now put me on this testosterone suppression, and I’ve been talking about libido in couples counseling for years. I now have no testosterone, and I now have no libido,” is what he says to me. I said, “Well, what is it?” He said, “There are 12 naked women, and they all are very attractive. One is carrying a hamburger, and all I’m doing is looking at the hamburger.” I said to him, “How do you feel about that?” He said, “It actually doesn’t bother me.”

There are, however, patients for whom that bother is extreme. You need to actually monitor and help them with couples counseling. Not only is it the exercise and the encouragement to exercise, but it’s talk about their sexual well-being and their partner’s relationship. You sometimes need to focus on that. But you’ve got to get them through the 2 years. Others actually get really depressed about it. Others get angry. Others get, “Eh, I’m getting much less whiplash. My life is a lot less complicated.” So that’s the other thing I think we should talk about.

Dan George, MD: That’s really interesting. I bring that up and I’ve seen that as well, and it is a struggle. Sometimes that is a reason to modify what we’re doing, but it’s certainly reason to counsel. For sure.

Transcript Edited for Clarity

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Transcript: 

Dan George, MD: Joe, if I could turn to you a little on this subject, because from a radiation standpoint, we’re really coupling 2 therapies: hormonal therapy and radiation therapy. A lot of people have focused on the local therapy. They tend to put this aside. Maybe for a lot of these issues I think, “Well, the primary care doctor will deal with it.” You heard what Chuck said. How do you incorporate that into your practice when you’re combining therapies?

Joe M. O’Sullivan, MD, FRCPI, FFRRSCI, FRCR: First, for our patients with higher-risk locally advanced disease, I think the evidence is extremely strong now that the combination of radiation and some form of androgen deprivation improves outcome. There’s no question about that. When I talk to a patient who’s at a slightly higher risk, whether it’s because of T3 disease or at least an 8 or above, I tell the patient that radiation on its own is not going to be enough. I describe different types of hormone therapy. Like Chuck, I also describe the lifestyle changes that are required to deal with that.

But I also sometimes consider using noncastration hormone therapy. For example, in Europe, we can use bicalutamide, 150 mg per day. It’s very effective, and it reduces some of the metabolic effect that you get with castration therapy. But I think it’s very important that patients understand the reasoning behind the hormone therapy. It’s to basically improve the results of local therapy. We know that hormone therapy dramatically improves it. We’ve seen this over many different trials, that the addition of hormone therapy to radiation, and the addition of radiation to hormone therapy dramatically improves survival. In fact, it’s probably 1 of the most dramatic randomized trial evidence of improved survival in prostate cancer that we have. I think the combination of hormones and radiation are 1 of the biggest reasons why we’re seeing a reduction in prostate cancer mortality overall.

Dan George, MD: Fair enough. Very good. Chris, when you’re dealing with hormonal therapy and radiation therapy, and you’re having a patient who’s struggling a little with these adverse effects, how does that factor in to how you manage it? Does it change the length of therapy you’re going to give this patient? Does it change the agents you’re using, as Joe said, or things like that? Any monitoring, like how Chuck talked about exercise? What are some of the things you counsel patients around what you can do to manage some of those issues?

Christopher Sweeney, MBBS: I’ll pick up on 1 thing and say this conversation may well actually also extend to the surgical setting if the neoadjuvant studies pan out. This conversation would be even more relevant as we intensify the hormonal therapy. So I just want to say this is not going to go away, it’s going to get more relevant, and underscore that. What I do is, I counsel patients on the adverse effects and I say, “This is what may happen, and whether we can get you through the whole period depends on how you tolerate this.” I set the expectation, “This is what we’d like to do, but if we get to a point where we’re increasing your comorbidities—which may outweigh the treatment benefit—we may have to adapt, improvise, overcome like the CIA [Central Intelligence Agency]. We have to realize that we have to individualize.

One other thing that I’m actually very clear about, what I’ve learned is that sexuality is also a major issue, and I monitor their emotional well-being. I have this great analogy from a patient of mine who shared this with me, and this is going to be a bit of a silly story, but it is very emphatic, and my patients understand it. “Chris, I’m a psychologist. You’ve now put me on this testosterone suppression, and I’ve been talking about libido in couples counseling for years. I now have no testosterone, and I now have no libido,” is what he says to me. I said, “Well, what is it?” He said, “There are 12 naked women, and they all are very attractive. One is carrying a hamburger, and all I’m doing is looking at the hamburger.” I said to him, “How do you feel about that?” He said, “It actually doesn’t bother me.”

There are, however, patients for whom that bother is extreme. You need to actually monitor and help them with couples counseling. Not only is it the exercise and the encouragement to exercise, but it’s talk about their sexual well-being and their partner’s relationship. You sometimes need to focus on that. But you’ve got to get them through the 2 years. Others actually get really depressed about it. Others get angry. Others get, “Eh, I’m getting much less whiplash. My life is a lot less complicated.” So that’s the other thing I think we should talk about.

Dan George, MD: That’s really interesting. I bring that up and I’ve seen that as well, and it is a struggle. Sometimes that is a reason to modify what we’re doing, but it’s certainly reason to counsel. For sure.

Transcript Edited for Clarity
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