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Sequencing Therapy With ADT Combinations

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: Wednesday, Apr 04, 2018



Transcript: 

Raoul S. Concepcion, MD, FACS: Neal, this concept that Dan just brought up—high-volume versus low-volume disease, greater than 4 in metastatic size—how successful, in your mind, have we been in terms of urologists in the community, larger practices, incorporating that definition to make these decision points for the addition of other therapies to androgen deprivation therapy?

Neal D. Shore, MD, FACS: I would say it’s completely artificial and arbitrary, and it makes no sense. It’s really limited by the inefficiencies of the scan technologies that we would use. But on the other side, the evidence only speaks to 4 or more bone lesions, usually some outside of the axial skeletal, as well, and/or visceral metastases.

So, the evidence kind of outweighs everything. But that said, as we get into more sophisticated scanning technologies, the absolute number becomes somewhat of an arbitrary issue. Given the breakthrough that we now have in ADT, with 6 cycles of docetaxel with no prednisone, interestingly, versus ADT and abiraterone, with a reduced dose of 5 mg of prednisone daily, where the forest plots are almost identical and all subplots are beneficial, what do you do now, Dan, when a patient shows up, assuming they’re fit? Docetaxel or abiraterone? How do you make your decision? Then what do you do after you go with one? How do you think about sequencing?

Daniel George, MD: That’s a great question. We don’t have head-to-head data. There’s really no data that I can speak to, to say that based on ‘this,’ that I’m going to use abiraterone or docetaxel. But we do have our own clinical experiences. For the most part, abiraterone is something that has been better tolerated in this setting. There are circumstances where that’s not the case. But starting out with an oral pill is something that we’ve been able to do. This is not FDA approved, in this space. It’s got NCCN criteria. There may be cost coverage issues. That has come up in some practices. But for the most part, at least at Duke, we’ve been able to treat patients. For the most part, we’re treating patients with abiraterone.

I’ve used docetaxel in my patients with visceral metastases—in particular, with liver metastases—when I have patients that have really dramatic disease biology or in patients where I’ve started with abiraterone and have not seen the kind of prostate-specific antigen decline in the first 2 to 3 months that I’m really looking for. Remember, the most prognostic indicators here are the rate of PSA decline and how low this gets. PSAs that don’t drop below 4.0 ng/mL have a particularly poor prognosis. We know that from data.

Neal D. Shore, MD, FACS: There’s a nice paper in this month’s Journal of Clinical Oncology, which follows up on looking at less than 0.2, 0.2 to 4, and above 4, and it’s actually very predictive of bad outcomes. But I think your initial question was a really good one. The busy urologist, who’s seeing these patients, can no longer just say, “OK, I’m going to start you on ADT. I’m going to watch your PSA come down. It’s all good.” if you have not had this shared decision discussion about this incredible level 1 evidence to combine with abiraterone or docetaxel, it is really not doing the patient a good service.

Raoul S. Concepcion, MD, FACS: Alec, you obviously have created your business model, in your clinic, where you’ve incorporated a medical oncologist in house. All of us, especially in the urology world, are trying to drive to some element of standardization of pathways. How have you guys incorporated this data? Again, these are the patients who primarily show up because they’ve been diagnosed in one fashion or another. They have to get a biopsy, so they’re showing up to us. What’s happening at Skyline Urology, in terms of the adoption of ADT plus one of these therapies, whether it be an oral agent or traditional chemotherapy?

Alec Koo, MD: I think this really points out the importance of taking a multidisciplinary approach to this disease state. Traditionally, these patients are in the urologist’s office because they’re referred to the urologist. They have a high PSA. The urologist does a biopsy. The urologist is the physician who is now making all of the decisions. I would not be surprised that there’s no urologist out there who simply would start the patient on ADT.

Obviously, in our practice, over the years, we’ve taken on a multidisciplinary growth. Our group is probably really more of a multispecialty group that’s geared toward treating urologic disease. We have radiation oncologists, medical oncologists, and pathologists. Internally, the referral process and the education process is much more fluid. Their pathways are implemented, so the referral process is going by the pathway. A lot of the pathway that is now enforced is probably more suggestive. But because of the knowledge that is disseminated, within our own group, we have medical oncology expertise so that these patients are properly channeled. As you know, you’re not giving chemotherapy. Oftentimes, that is not really part of your armamentarium. This is really a disservice to the patient.

Raoul S. Concepcion, MD, FACS: So, in your particular pathway, at Skyline Urology, if a patient does have newly diagnosed, high-grade prostate cancer with metastatic disease on a bone scan CT, is the suggested pathway to then make sure that they see your medical oncologist at Skyline?

Alec Koo, MD: Absolutely.

Raoul S. Concepcion, MD, FACS: What do you think the uptake is on that?

Alec Koo, MD: It’s variable based on the individual urologist. There’s a certain amount of inertia, stationary or hubris. I think it’s a slow process. There are early, quick adopters and then there are those who gradually come along. When you have a multidisciplinary approach within your own group, it allows for a much easier adoption of that approach.

Daniel George, MD: I would add that it’s not all on the urologist. There are medical oncologists out there who are eager to see and treat these patients. But when you have a dedicated medical oncologist that is affiliated with your group, who is interested in this patient population, I think it really behooves us to work together. So, I think that finding those relationships, and cultivating that when you can, is important. And if it’s there, use it. If it isn’t, you can’t blame the urologist for something that they don’t have access to. I think that’s something that has to evolve on both sides.

Transcript Edited for Clarity 

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Transcript: 

Raoul S. Concepcion, MD, FACS: Neal, this concept that Dan just brought up—high-volume versus low-volume disease, greater than 4 in metastatic size—how successful, in your mind, have we been in terms of urologists in the community, larger practices, incorporating that definition to make these decision points for the addition of other therapies to androgen deprivation therapy?

Neal D. Shore, MD, FACS: I would say it’s completely artificial and arbitrary, and it makes no sense. It’s really limited by the inefficiencies of the scan technologies that we would use. But on the other side, the evidence only speaks to 4 or more bone lesions, usually some outside of the axial skeletal, as well, and/or visceral metastases.

So, the evidence kind of outweighs everything. But that said, as we get into more sophisticated scanning technologies, the absolute number becomes somewhat of an arbitrary issue. Given the breakthrough that we now have in ADT, with 6 cycles of docetaxel with no prednisone, interestingly, versus ADT and abiraterone, with a reduced dose of 5 mg of prednisone daily, where the forest plots are almost identical and all subplots are beneficial, what do you do now, Dan, when a patient shows up, assuming they’re fit? Docetaxel or abiraterone? How do you make your decision? Then what do you do after you go with one? How do you think about sequencing?

Daniel George, MD: That’s a great question. We don’t have head-to-head data. There’s really no data that I can speak to, to say that based on ‘this,’ that I’m going to use abiraterone or docetaxel. But we do have our own clinical experiences. For the most part, abiraterone is something that has been better tolerated in this setting. There are circumstances where that’s not the case. But starting out with an oral pill is something that we’ve been able to do. This is not FDA approved, in this space. It’s got NCCN criteria. There may be cost coverage issues. That has come up in some practices. But for the most part, at least at Duke, we’ve been able to treat patients. For the most part, we’re treating patients with abiraterone.

I’ve used docetaxel in my patients with visceral metastases—in particular, with liver metastases—when I have patients that have really dramatic disease biology or in patients where I’ve started with abiraterone and have not seen the kind of prostate-specific antigen decline in the first 2 to 3 months that I’m really looking for. Remember, the most prognostic indicators here are the rate of PSA decline and how low this gets. PSAs that don’t drop below 4.0 ng/mL have a particularly poor prognosis. We know that from data.

Neal D. Shore, MD, FACS: There’s a nice paper in this month’s Journal of Clinical Oncology, which follows up on looking at less than 0.2, 0.2 to 4, and above 4, and it’s actually very predictive of bad outcomes. But I think your initial question was a really good one. The busy urologist, who’s seeing these patients, can no longer just say, “OK, I’m going to start you on ADT. I’m going to watch your PSA come down. It’s all good.” if you have not had this shared decision discussion about this incredible level 1 evidence to combine with abiraterone or docetaxel, it is really not doing the patient a good service.

Raoul S. Concepcion, MD, FACS: Alec, you obviously have created your business model, in your clinic, where you’ve incorporated a medical oncologist in house. All of us, especially in the urology world, are trying to drive to some element of standardization of pathways. How have you guys incorporated this data? Again, these are the patients who primarily show up because they’ve been diagnosed in one fashion or another. They have to get a biopsy, so they’re showing up to us. What’s happening at Skyline Urology, in terms of the adoption of ADT plus one of these therapies, whether it be an oral agent or traditional chemotherapy?

Alec Koo, MD: I think this really points out the importance of taking a multidisciplinary approach to this disease state. Traditionally, these patients are in the urologist’s office because they’re referred to the urologist. They have a high PSA. The urologist does a biopsy. The urologist is the physician who is now making all of the decisions. I would not be surprised that there’s no urologist out there who simply would start the patient on ADT.

Obviously, in our practice, over the years, we’ve taken on a multidisciplinary growth. Our group is probably really more of a multispecialty group that’s geared toward treating urologic disease. We have radiation oncologists, medical oncologists, and pathologists. Internally, the referral process and the education process is much more fluid. Their pathways are implemented, so the referral process is going by the pathway. A lot of the pathway that is now enforced is probably more suggestive. But because of the knowledge that is disseminated, within our own group, we have medical oncology expertise so that these patients are properly channeled. As you know, you’re not giving chemotherapy. Oftentimes, that is not really part of your armamentarium. This is really a disservice to the patient.

Raoul S. Concepcion, MD, FACS: So, in your particular pathway, at Skyline Urology, if a patient does have newly diagnosed, high-grade prostate cancer with metastatic disease on a bone scan CT, is the suggested pathway to then make sure that they see your medical oncologist at Skyline?

Alec Koo, MD: Absolutely.

Raoul S. Concepcion, MD, FACS: What do you think the uptake is on that?

Alec Koo, MD: It’s variable based on the individual urologist. There’s a certain amount of inertia, stationary or hubris. I think it’s a slow process. There are early, quick adopters and then there are those who gradually come along. When you have a multidisciplinary approach within your own group, it allows for a much easier adoption of that approach.

Daniel George, MD: I would add that it’s not all on the urologist. There are medical oncologists out there who are eager to see and treat these patients. But when you have a dedicated medical oncologist that is affiliated with your group, who is interested in this patient population, I think it really behooves us to work together. So, I think that finding those relationships, and cultivating that when you can, is important. And if it’s there, use it. If it isn’t, you can’t blame the urologist for something that they don’t have access to. I think that’s something that has to evolve on both sides.

Transcript Edited for Clarity 
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