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Utilizing AR-Targeted Therapies in CRPC

Panelists: Raoul S. Concepcion, MD, FACS, Comprehensive Prostate Center; Daniel George, MD, Duke Cancer Institute; Alec Koo, MD, Skyline Urology; Phillip Koo, MD, MD Anderson Cancer Center; Neal D. Shore, MD, FACS, Carolina Urologic Research Center
Published: Monday, May 07, 2018



Transcript: 

Raoul S. Concepcion, MD, FACS: Alec, assuming that both of these agents will probably get an indication approval for use in the M0 castration-resistant prostate cancer patient, what do you think the likelihood is of community urologists or medical oncologists saying, “I’m not going to scan. I’m just going to give them one of these oral agents?” They see this definition. The prostate-specific antigen is going up. They’re asymptomatic. You now have, potentially, a couple of agents that are approved.

Alec Koo, MD: Again, I think that the temptation is great. Urologists traditionally have been very comfortable with giving bicalutamide (Casodex). I still see patients from some of my partners, or some of my retired partners, who have been on bicalutamide for a long time. A lot of urologists are just comfortable with the concept of giving an oral anti-androgen in various settings. Our approach should really continue to be done in a systemized fashion. I assume that PSA doubling time is going to be an essential factor in determining eligibility for treatment. Most urologists aren’t calculating PSA doubling time. But in a systemized navigator program, the routine checking of PSA level and calculation of PSA doubling time should be incorporated, based on whatever the criteria are for these medications.

Raoul S. Concepcion, MD, FACS: What about the imaging? What about the baseline scan? I can see this. I can see a busy urologist. His PSA’s going up. He doesn’t want to spend the time to have this lengthy discussion.

Daniel George, MD: That’s how you use bicalutamide, right? In this setting, right? These guys wouldn’t necessarily go and restage them all. They’d just say, “PSA is up. I’ll add bicalutamide.”

Raoul S. Concepcion, MD, FACS: Right.

Alec Koo, MD: What is wrong with that approach, then? Even in a systemized fashion, you’re tracking all of your patients. You’re calculating doubling time. These are CRPC patients who now have this PSA doubling time. They just start them on medication.

Raoul S. Concepcion, MD, FACS: To me, it’s a problem of not knowing where they truly stand, from a metastatic standpoint, at baseline. You can’t really know when they’ve actually progressed if you don’t have a baseline scan.

Alec Koo, MD: I think the reality is that for a lot of these patients, we’ve been obtaining a bone scan and CT scan. Obviously, they’ve been negative, so they’re still in this M0 space. You hit the doubling time threshold. You start treating them. And so, the question is, do we use more advanced imaging to try to document metastasis? Or do you just continue to do the bone scan, CT scan, knowing that it’s not sensitive? It is not going to detect metastasis, but you have the new medication that you, in fact, can use.

Neal D. Shore, MD, FACS: I would hope that doesn’t happen—that people just reflexively put folks on a drug. The criteria that we typically talk about suggest making a change to the next line of therapy if the patient is no longer clinically benefitting, which has a sort of vagueness to it, but is symptomatic. Number 2 is new lesions. How do you know if there are new lesions if you didn’t get baseline scans to know where your existing lesions were? A subset to that argument is, I like to know if somebody has got their spine riddled with disease versus their liver versus soft tissue adenopathy based upon correlation with their symptomatology and other adjuvant treatments that I might be thinking about, later on. And, of course, if you’re a trialist, you’d want to know where their disease is, too. Then, the third part is, where your laboratory values are, if they’re outside normal range, where your scans showed the disease was. So, I hope that our colleagues don’t do this reflexively because of being too busy.

Daniel George, MD: Can I ask one other question related to this? I think what Neal brings up is really important. If, for nothing else, it’s helpful for the prognosis. But I think it is helpful for future comparisons as well. The other aspect of this was the safety. As urologists, how do you all feel about this? Because it’s not what you think. It’s not necessarily safety totally directed to the therapy. Yes, there were slightly higher increases of fracture, dizziness, falls, or fatigue.

But, to me, the concerning things were the deaths. There were deaths on study. In both studies, you see deaths of about 3% to 5% in both arms—the placebo and the treated arm. If you look at the treated arm, these patients are on treatment for 2 years longer. So, naturally, they’re going to have some deaths on treatment that are unrelated to the drug. These are kind of natural history deaths. They can be caused by things like pneumonia, other infections, cardiovascular conditions or stroke, other cancers, or even other complications. When we look at patients who aren’t part of clinical trials, they tend to have more issues that would have excluded them.

So, my question is, if you know that 1 in 20 is going to die from other causes during the time that you’re following them, is this a population of patients that you want to involve in multidisciplinary care? Palliative care and some of the other kinds of hospice and other services that can kind of go along with this? Or is this a population in which you’re comfortable saying, “You know, I’ll just manage them. I’ll leave it to the internist to deal with these other issues?” It seems like whoever is sort of actively managing this is going to see the patient more often than almost any other doctor during that timeframe. They kind of carry that responsibility.

Raoul S. Concepcion, MD, FACS: Alec, you’re in a great position to actually address this because your practice is one of the only 2 community practices that are actually enrolled in the Oncology Care Model (OCM). What is your response in regard to Dan’s question or comment?

Alec Koo, MD: I really have to think about this one. First of all, the incidence of grade 3/4 toxicities is low. They’re in the order of 2% to 3%.

Daniel George, MD: Yes.

Alec Koo, MD: Right. So, the drugs, themselves, are fairly safe. There is a certain type of death that is unpredictable. But if you have a patient who, in fact, has a poor performance status, who looks sick, I think that does come to the judgment of the physician, of whether or not to start this medication. It’s an incredibly complex question. The patient could be there with family. The PSA is rising. They want dad or grandfather treated. They’re focusing on that. All of these factors come into play. At the end of the day, it probably really only affects a small percentage of all of the patients.

Daniel George, MD: It’s hard to do that in 3 minutes.

Raoul S. Concepcion, MD, FACS: Right. But, I think you’re right. Great points. As Phil said in his talk, we really do have to pay more attention to the benefits, the risks/benefits, and the quality of life issues that come along as we manage these patients. Great discussion.

Transcript Edited for Clarity 

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Transcript: 

Raoul S. Concepcion, MD, FACS: Alec, assuming that both of these agents will probably get an indication approval for use in the M0 castration-resistant prostate cancer patient, what do you think the likelihood is of community urologists or medical oncologists saying, “I’m not going to scan. I’m just going to give them one of these oral agents?” They see this definition. The prostate-specific antigen is going up. They’re asymptomatic. You now have, potentially, a couple of agents that are approved.

Alec Koo, MD: Again, I think that the temptation is great. Urologists traditionally have been very comfortable with giving bicalutamide (Casodex). I still see patients from some of my partners, or some of my retired partners, who have been on bicalutamide for a long time. A lot of urologists are just comfortable with the concept of giving an oral anti-androgen in various settings. Our approach should really continue to be done in a systemized fashion. I assume that PSA doubling time is going to be an essential factor in determining eligibility for treatment. Most urologists aren’t calculating PSA doubling time. But in a systemized navigator program, the routine checking of PSA level and calculation of PSA doubling time should be incorporated, based on whatever the criteria are for these medications.

Raoul S. Concepcion, MD, FACS: What about the imaging? What about the baseline scan? I can see this. I can see a busy urologist. His PSA’s going up. He doesn’t want to spend the time to have this lengthy discussion.

Daniel George, MD: That’s how you use bicalutamide, right? In this setting, right? These guys wouldn’t necessarily go and restage them all. They’d just say, “PSA is up. I’ll add bicalutamide.”

Raoul S. Concepcion, MD, FACS: Right.

Alec Koo, MD: What is wrong with that approach, then? Even in a systemized fashion, you’re tracking all of your patients. You’re calculating doubling time. These are CRPC patients who now have this PSA doubling time. They just start them on medication.

Raoul S. Concepcion, MD, FACS: To me, it’s a problem of not knowing where they truly stand, from a metastatic standpoint, at baseline. You can’t really know when they’ve actually progressed if you don’t have a baseline scan.

Alec Koo, MD: I think the reality is that for a lot of these patients, we’ve been obtaining a bone scan and CT scan. Obviously, they’ve been negative, so they’re still in this M0 space. You hit the doubling time threshold. You start treating them. And so, the question is, do we use more advanced imaging to try to document metastasis? Or do you just continue to do the bone scan, CT scan, knowing that it’s not sensitive? It is not going to detect metastasis, but you have the new medication that you, in fact, can use.

Neal D. Shore, MD, FACS: I would hope that doesn’t happen—that people just reflexively put folks on a drug. The criteria that we typically talk about suggest making a change to the next line of therapy if the patient is no longer clinically benefitting, which has a sort of vagueness to it, but is symptomatic. Number 2 is new lesions. How do you know if there are new lesions if you didn’t get baseline scans to know where your existing lesions were? A subset to that argument is, I like to know if somebody has got their spine riddled with disease versus their liver versus soft tissue adenopathy based upon correlation with their symptomatology and other adjuvant treatments that I might be thinking about, later on. And, of course, if you’re a trialist, you’d want to know where their disease is, too. Then, the third part is, where your laboratory values are, if they’re outside normal range, where your scans showed the disease was. So, I hope that our colleagues don’t do this reflexively because of being too busy.

Daniel George, MD: Can I ask one other question related to this? I think what Neal brings up is really important. If, for nothing else, it’s helpful for the prognosis. But I think it is helpful for future comparisons as well. The other aspect of this was the safety. As urologists, how do you all feel about this? Because it’s not what you think. It’s not necessarily safety totally directed to the therapy. Yes, there were slightly higher increases of fracture, dizziness, falls, or fatigue.

But, to me, the concerning things were the deaths. There were deaths on study. In both studies, you see deaths of about 3% to 5% in both arms—the placebo and the treated arm. If you look at the treated arm, these patients are on treatment for 2 years longer. So, naturally, they’re going to have some deaths on treatment that are unrelated to the drug. These are kind of natural history deaths. They can be caused by things like pneumonia, other infections, cardiovascular conditions or stroke, other cancers, or even other complications. When we look at patients who aren’t part of clinical trials, they tend to have more issues that would have excluded them.

So, my question is, if you know that 1 in 20 is going to die from other causes during the time that you’re following them, is this a population of patients that you want to involve in multidisciplinary care? Palliative care and some of the other kinds of hospice and other services that can kind of go along with this? Or is this a population in which you’re comfortable saying, “You know, I’ll just manage them. I’ll leave it to the internist to deal with these other issues?” It seems like whoever is sort of actively managing this is going to see the patient more often than almost any other doctor during that timeframe. They kind of carry that responsibility.

Raoul S. Concepcion, MD, FACS: Alec, you’re in a great position to actually address this because your practice is one of the only 2 community practices that are actually enrolled in the Oncology Care Model (OCM). What is your response in regard to Dan’s question or comment?

Alec Koo, MD: I really have to think about this one. First of all, the incidence of grade 3/4 toxicities is low. They’re in the order of 2% to 3%.

Daniel George, MD: Yes.

Alec Koo, MD: Right. So, the drugs, themselves, are fairly safe. There is a certain type of death that is unpredictable. But if you have a patient who, in fact, has a poor performance status, who looks sick, I think that does come to the judgment of the physician, of whether or not to start this medication. It’s an incredibly complex question. The patient could be there with family. The PSA is rising. They want dad or grandfather treated. They’re focusing on that. All of these factors come into play. At the end of the day, it probably really only affects a small percentage of all of the patients.

Daniel George, MD: It’s hard to do that in 3 minutes.

Raoul S. Concepcion, MD, FACS: Right. But, I think you’re right. Great points. As Phil said in his talk, we really do have to pay more attention to the benefits, the risks/benefits, and the quality of life issues that come along as we manage these patients. Great discussion.

Transcript Edited for Clarity 
View Conference Coverage
Online CME Activities
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
Community Practice Connections™: Precision Medicine for Community Oncologists: Assessing the Role of Tumor-Testing Technologies in Cancer CareNov 30, 20181.0
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