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ADT and Cardiovascular Risk in Prostate Cancer: Q&A

Insights From: Dipti Gupta, MD, MPH, Memorial Sloan Kettering Cancer Center; Susan Slovin, MD, PhD, Memorial Sloan Kettering Cancer Center
Published: Wednesday, May 30, 2018



Transcript: 

Dipti Gupta, MD, MPH: We will now move on and answer some of the questions provided by our audience. Dr. Slovin, is it better to undergo treatment with an antagonist or an agonist, or can surgical removal of the testes (orchiectomy) result in fewer side effects?

Susan Slovin, MD, PhD: All 3 approaches are going to reduce the serum testosterone level, although we do know that GnRH antagonists seem to drop it well below 20. The main concern is, what kind of side effects are we talking about? All 3 approaches are going to cause either hot flushes, centripetal obesity, the potential for metabolic syndrome, mood swings, weight gain, and the like. However, if it comes down to the cardiovascular benefit, we really won’t know until that PRONOUNCE trial is completed.

Dipti Gupta, MD, MPH: That’s right.

Susan Slovin, MD, PhD: That’s all we can do for now.

Dipti Gupta, MD, MPH: That’s right.

Susan Slovin, MD, PhD: Dr. Gupta, how quickly could androgen deprivation therapy raise the risk for a cardiovascular event? Who’s at high risk? Who’s going to have something that we’re completely unprepared to deal with?

Dipti Gupta, MD, MPH: I think it is important to categorize who is at high risk. It’s an extremely important area to focus on. As data have shown us, these patients may be patients who are older, who already have risk factors, especially patients who have established coronary artery disease or have had revascularization. The highest-risk patients are going to be the ones who have had a cardiovascular event happen to them within 6 months to a year before starting ADT.

Susan Slovin, MD, PhD: So, you’re less concerned if somebody had a bypass 10 or 15 years ago or a stent?

Dipti Gupta, MD, MPH: I’m still concerned. I would still want them to be optimized, in terms of their risk factors and their medical management. But I think the patients who we really need to sit down with and clearly identify as high risk are those who say, “I had a heart attack 6 months ago—I got a stent” or “I was admitted for heart failure—I am 85 years old.” So, those are going to be your highest-risk patients.
How quickly could ADT increase the risk of an event? It would appear that one would like to think that it takes much longer, but it turns out that it can actually happen within 6 months. So, it doesn’t take long for bad things to happen.

Let’s go on to our next question. What should I tell my primary care doctor/internist about my cancer treatments? Should my oncologist now monitor my blood pressure and cholesterol? This is a fantastic question.

Susan Slovin, MD, PhD: It’s fantastic, absolutely. I’m going to answer the bottom second question first, which is, should my oncologist monitor my blood pressure? Patients erroneously think that it’s now my job to be their primary care physician, their proctologist, their sex therapist, their neurosurgeon, their dentist. It’s all very true. The reality is, we need a multidisciplinary approach. It’s imperative that we know who the primary care physician/internist is and that we send notes. The first part of the question is, what should I tell my primary care doctor or internist about my treatment? You really need to make sure that people understand what they’re getting or what you’re giving them. Recently, one of my patients was hospitalized for, believe it or not, a coronary event. I got a call from the house staff. They said to me, “The patient told us he has been on chemotherapy for the last couple of years.” In reality, he was on an antiandrogen that had no bearing on chemotherapy at all. You tell people things. You give them fact cards to educate them. The reality is, it’s very important that you have a relationship with the outside doctor or at least a family member so they know what’s going on.

Dipti Gupta, MD, MPH: Yes, absolutely.

Susan Slovin, MD, PhD: Are there any convincing data that would really point toward increased cardiovascular disease? For people with prostate cancer who go on ADT, is it worse? Is it still controversial? Do we know? Do we not know? It’s hard to conclude when we have all of these different papers.

Dipti Gupta, MD, MPH: Based on everything that we know, we badly need prospective data to sort of come to some kind of an evidence-based decision. The jury is still out as to whether there is increased cardiovascular mortality with ADT. It would make sense, going through everything that we have seen and we now know, but most of our data and most of our positive associations, let’s remember, are coming from these large-scale observational trials. And as the history of medicine would point out, that’s just the second-best way of doing things. We have to study patients prospectively to really get to the depth and the bottom of some of these more controversial questions, so I look forward to the PRONOUNCE trial results.

Susan Slovin, MD, PhD: As we all do.

Dipti Gupta, MD, MPH: Let’s go to the next question. What is the role for androgen blockade and radiation at present in metastatic prostate cancer patients? What is the duration of ADT in a favorable intermediate-risk patient—4 or 6 months?

Susan Slovin, MD, PhD: I think we have to dissect the first question. Androgen deprivation therapy still is the mainstay of treatment for people with metastatic prostate cancer. I think what got a little confused in the question was patients who had intermediate risk, as defined as Gleason 7, or very high risk. By high risk, we’re not talking about somebody dying. We’re talking about the high risk of their disease coming back. Hormonal therapy for 2 or 3 months, initially—just to downsize the gland and get rid of any micrometastatic disease—is done, but the hormones remain on board during at least 6 to 8 weeks of radiation. And then the real concern is, how long do you maintain people on hormonal therapy after radiation is completed? In the literature, based on randomized trial, what had been initially accepted was 3 years. Now, for a young man—let’s say age 50 or 60—that’s a lot of years to be on hormonal therapy, not to mention the hot flushes and the possibility of their disease becoming resistant. And the longer they’re on therapy, the harder it is to recoup their testosterone levels, which would be of cardiovascular benefit to the patient, irrespective of their cardiovascular risk.

Again, it depends on the clinical situation, but I think that, very often, when we give hormonal therapy to patients, our goal is disease control and prevention of future recurrences. But at the same time, we don’t realize that we don’t always have to follow the rule book. We can negotiate a little bit. It doesn’t have to be exactly at 3 years—it could be a little bit less. It really depends on the tolerance. We really want people to have the maximal treatment, but the maximal may not be the beneficial if there’s a pre-existing problem.

Dipti Gupta, MD, MPH: Absolutely.

Susan Slovin, MD, PhD: What about screening patients? How do we screen patients, manage them, and counsel them prior to and during ADT? There had been some concerns that there was no benefit, based on that original study from 2010, and that we didn’t really know what to do with patients. But now, 8 years later, there certainly has to be something in an algorithm that would perhaps be beneficial…?

Dipti Gupta, MD, MPH: Let’s just jump into this algorithm. I mentioned this clinical update that had appeared in the American Heart Association’s journal called Circulation. I think this is a very, very good practical scheme for patients and providers to understand and sort of follow. In the diagnosis of prostate cancer, if the patient is going to start ADT, we would refer them to a cardiology clinic if there is concern of presence or risk of cardiovascular disease. I would go so far as to say primary prevention can be done with primary care providers, and secondary prevention can be sent to cardiology or cardio-oncology clinics. And then, for pre-existing cardiovascular disease, you do guideline concordant medical management. For patients, you ensure that they have a baseline lipid panel or hemoglobin A1C or fasting lipid profile and make sure that there are no unstable syndromes that need to be addressed before jumping into cancer therapy. Think about putting them on an aspirin regimen—81 mg—and then go through the ABCDE schema that we have talked about.

This is the last question for the day, and this question pertains to avoidance of weight gain associated with hormonal therapy.

Susan Slovin, MD, PhD: Well, that’s the million-dollar question that patients come in with. How do I avoid getting a little potbelly? How do I feel better? Based on a lot of the data that you’ve shown, obviously doing aerobics and resistance training is probably best. Stay off your tush, essentially, and be active.

Dipti Gupta, MD, MPH: Yes. This has been an excellent discussion. We hope that you found the information that we just reviewed to be valuable to your clinical practice. Thank you for watching OncLive® News Network.

Susan Slovin, MD, PhD: Thank you.

Transcript Edited for Clarity 
Slider Left
Slider Right


Transcript: 

Dipti Gupta, MD, MPH: We will now move on and answer some of the questions provided by our audience. Dr. Slovin, is it better to undergo treatment with an antagonist or an agonist, or can surgical removal of the testes (orchiectomy) result in fewer side effects?

Susan Slovin, MD, PhD: All 3 approaches are going to reduce the serum testosterone level, although we do know that GnRH antagonists seem to drop it well below 20. The main concern is, what kind of side effects are we talking about? All 3 approaches are going to cause either hot flushes, centripetal obesity, the potential for metabolic syndrome, mood swings, weight gain, and the like. However, if it comes down to the cardiovascular benefit, we really won’t know until that PRONOUNCE trial is completed.

Dipti Gupta, MD, MPH: That’s right.

Susan Slovin, MD, PhD: That’s all we can do for now.

Dipti Gupta, MD, MPH: That’s right.

Susan Slovin, MD, PhD: Dr. Gupta, how quickly could androgen deprivation therapy raise the risk for a cardiovascular event? Who’s at high risk? Who’s going to have something that we’re completely unprepared to deal with?

Dipti Gupta, MD, MPH: I think it is important to categorize who is at high risk. It’s an extremely important area to focus on. As data have shown us, these patients may be patients who are older, who already have risk factors, especially patients who have established coronary artery disease or have had revascularization. The highest-risk patients are going to be the ones who have had a cardiovascular event happen to them within 6 months to a year before starting ADT.

Susan Slovin, MD, PhD: So, you’re less concerned if somebody had a bypass 10 or 15 years ago or a stent?

Dipti Gupta, MD, MPH: I’m still concerned. I would still want them to be optimized, in terms of their risk factors and their medical management. But I think the patients who we really need to sit down with and clearly identify as high risk are those who say, “I had a heart attack 6 months ago—I got a stent” or “I was admitted for heart failure—I am 85 years old.” So, those are going to be your highest-risk patients.
How quickly could ADT increase the risk of an event? It would appear that one would like to think that it takes much longer, but it turns out that it can actually happen within 6 months. So, it doesn’t take long for bad things to happen.

Let’s go on to our next question. What should I tell my primary care doctor/internist about my cancer treatments? Should my oncologist now monitor my blood pressure and cholesterol? This is a fantastic question.

Susan Slovin, MD, PhD: It’s fantastic, absolutely. I’m going to answer the bottom second question first, which is, should my oncologist monitor my blood pressure? Patients erroneously think that it’s now my job to be their primary care physician, their proctologist, their sex therapist, their neurosurgeon, their dentist. It’s all very true. The reality is, we need a multidisciplinary approach. It’s imperative that we know who the primary care physician/internist is and that we send notes. The first part of the question is, what should I tell my primary care doctor or internist about my treatment? You really need to make sure that people understand what they’re getting or what you’re giving them. Recently, one of my patients was hospitalized for, believe it or not, a coronary event. I got a call from the house staff. They said to me, “The patient told us he has been on chemotherapy for the last couple of years.” In reality, he was on an antiandrogen that had no bearing on chemotherapy at all. You tell people things. You give them fact cards to educate them. The reality is, it’s very important that you have a relationship with the outside doctor or at least a family member so they know what’s going on.

Dipti Gupta, MD, MPH: Yes, absolutely.

Susan Slovin, MD, PhD: Are there any convincing data that would really point toward increased cardiovascular disease? For people with prostate cancer who go on ADT, is it worse? Is it still controversial? Do we know? Do we not know? It’s hard to conclude when we have all of these different papers.

Dipti Gupta, MD, MPH: Based on everything that we know, we badly need prospective data to sort of come to some kind of an evidence-based decision. The jury is still out as to whether there is increased cardiovascular mortality with ADT. It would make sense, going through everything that we have seen and we now know, but most of our data and most of our positive associations, let’s remember, are coming from these large-scale observational trials. And as the history of medicine would point out, that’s just the second-best way of doing things. We have to study patients prospectively to really get to the depth and the bottom of some of these more controversial questions, so I look forward to the PRONOUNCE trial results.

Susan Slovin, MD, PhD: As we all do.

Dipti Gupta, MD, MPH: Let’s go to the next question. What is the role for androgen blockade and radiation at present in metastatic prostate cancer patients? What is the duration of ADT in a favorable intermediate-risk patient—4 or 6 months?

Susan Slovin, MD, PhD: I think we have to dissect the first question. Androgen deprivation therapy still is the mainstay of treatment for people with metastatic prostate cancer. I think what got a little confused in the question was patients who had intermediate risk, as defined as Gleason 7, or very high risk. By high risk, we’re not talking about somebody dying. We’re talking about the high risk of their disease coming back. Hormonal therapy for 2 or 3 months, initially—just to downsize the gland and get rid of any micrometastatic disease—is done, but the hormones remain on board during at least 6 to 8 weeks of radiation. And then the real concern is, how long do you maintain people on hormonal therapy after radiation is completed? In the literature, based on randomized trial, what had been initially accepted was 3 years. Now, for a young man—let’s say age 50 or 60—that’s a lot of years to be on hormonal therapy, not to mention the hot flushes and the possibility of their disease becoming resistant. And the longer they’re on therapy, the harder it is to recoup their testosterone levels, which would be of cardiovascular benefit to the patient, irrespective of their cardiovascular risk.

Again, it depends on the clinical situation, but I think that, very often, when we give hormonal therapy to patients, our goal is disease control and prevention of future recurrences. But at the same time, we don’t realize that we don’t always have to follow the rule book. We can negotiate a little bit. It doesn’t have to be exactly at 3 years—it could be a little bit less. It really depends on the tolerance. We really want people to have the maximal treatment, but the maximal may not be the beneficial if there’s a pre-existing problem.

Dipti Gupta, MD, MPH: Absolutely.

Susan Slovin, MD, PhD: What about screening patients? How do we screen patients, manage them, and counsel them prior to and during ADT? There had been some concerns that there was no benefit, based on that original study from 2010, and that we didn’t really know what to do with patients. But now, 8 years later, there certainly has to be something in an algorithm that would perhaps be beneficial…?

Dipti Gupta, MD, MPH: Let’s just jump into this algorithm. I mentioned this clinical update that had appeared in the American Heart Association’s journal called Circulation. I think this is a very, very good practical scheme for patients and providers to understand and sort of follow. In the diagnosis of prostate cancer, if the patient is going to start ADT, we would refer them to a cardiology clinic if there is concern of presence or risk of cardiovascular disease. I would go so far as to say primary prevention can be done with primary care providers, and secondary prevention can be sent to cardiology or cardio-oncology clinics. And then, for pre-existing cardiovascular disease, you do guideline concordant medical management. For patients, you ensure that they have a baseline lipid panel or hemoglobin A1C or fasting lipid profile and make sure that there are no unstable syndromes that need to be addressed before jumping into cancer therapy. Think about putting them on an aspirin regimen—81 mg—and then go through the ABCDE schema that we have talked about.

This is the last question for the day, and this question pertains to avoidance of weight gain associated with hormonal therapy.

Susan Slovin, MD, PhD: Well, that’s the million-dollar question that patients come in with. How do I avoid getting a little potbelly? How do I feel better? Based on a lot of the data that you’ve shown, obviously doing aerobics and resistance training is probably best. Stay off your tush, essentially, and be active.

Dipti Gupta, MD, MPH: Yes. This has been an excellent discussion. We hope that you found the information that we just reviewed to be valuable to your clinical practice. Thank you for watching OncLive® News Network.

Susan Slovin, MD, PhD: Thank you.

Transcript Edited for Clarity 
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TitleExpiration DateCME Credits
Community Practice Connections™: Personalized Sequencing in Castration-Resistant Prostate Cancer: Bridging the Latest Evidence to the Bedside in Clinical ManagementAug 25, 20181.5
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