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Risk Stratification in Nonmetastatic Prostate Cancer

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: Tuesday, Mar 20, 2018



Transcript:

Raoul S. Concepcion, MD, FACS: We’ve sort of alluded to some of this next-generation imaging, and we’re trying to adopt that nomenclature. In your mind, what’s out there? What’s available, especially for utilization in this particular space?

Phillip Koo, MD: First off, I love this discussion about multidisciplinary care, because that’s clearly how we can add a lot of value to our patient care. And when we talk about imaging, specifically, I think imaging is a team sport. Right now, we’re in the process of showing a success story, when it comes to imaging in a disease state that we had not had as much progress in over the past 20 years.

When it comes to imaging in the biochemical space, I think there’s been a lot of advancement, a lot of excitement, especially in the US, now that we have Axumin, which is fluciclovine, available, FDA approved, and reimbursed by the CMS (Centers for Medicare & Medicaid Services). It’s an amino acid analog that’s been shown to detect disease much sooner than any other tool that we’ve had in the past. Alec pointed out the limitations with bone scans and CTs, and we’ve had to deal with that. We’ve done a great job. But I think this is really where we take the next step.

Some of the data, with regard to fluciclovine, has shown that in one multisite trial, in the lowest quartile—PSA levels less than 0.79—detection rates were around 41%. And if we move on to Gallium-68 PSMA, there are reports of detection rates under a PSA level of 0.5 of around 40% to 50%. These are unheard of, in terms of PSA levels. I think this is extremely encouraging, and this really changes how we need to think about patients. As Neal mentioned, this idea of oligometastatic disease is going to be a bigger part of all of our practices, and we’re already seeing this. People are talking about it, and there are a lot of questions. I think it’s great that we’re having these discussions, because we need those answers.

Raoul S. Concepcion, MD, FACS: Phil, in the data that you quoted, those were for patients who have been definitively treated for their primary, but have a rising PSA. Those are not patients on androgen deprivation therapy?

Phillip Koo, MD: Correct, just elevated PSA. And currently, the label for Axumin is elevated PSA following prior therapy. So, that’s the ideal space.

Raoul S. Concepcion, MD, FACS: What is the availability of Axumin, nationwide?

Phillip Koo, MD: Currently, to my knowledge, I think there are probably over 400 sites that are offering Axumin in their PET/CT facilities. I think a lot of it is just a matter of distribution. Given the fact that Axumin is based on an F-18 isotope, it has a roughly 2-hour half-life, which allows it to be distributed pretty much all across the country. That’s what really allows it to be commercialized. A lot of us are familiar with Choline C-11. The biggest limitation with that was that the half-life was 20 minutes, which really required an onsite cyclotron facility. This puts it out of the reach of 99.9% of imaging facilities across the country.

Raoul S. Concepcion, MD, FACS: So, the real impact of these scans, essentially, is given the increased sensitivity of the scan to detect what has basically always been thought of as potentially microscopic disease, and that brings up this whole concept of oligometastatic disease. Obviously, this can potentially change therapy, whether it’s going to potentially identify a lymph node for surgery. You may find a limited distribution of bony metastases that could be amendable to potentially spot radiation, and those types of things. Besides the Axumin scan, what else, right now, is FDA approved in this particular setting?

Phillip Koo, MD: Choline C-11 is approved, but it’s approved based on facilities. The Mayo Clinic is one site where it does have FDA approval. There are other sites that will offer it, but not under FDA approval. I think the future that a lot of us are very excited about is in using Gallium-68 PSMA, which currently does not have FDA approval, but is offered, I think, in 4 sites across the country. Eventually, we foresee that being the next novel imaging tool that gets FDA approval. Hopefully, it will be paid for by our payers, as well.

Raoul S. Concepcion, MD, FACS: Dan, do you have availability of Axumin at Duke?

Daniel George, MD: We do. We’ve been doing it for probably about 9 months or so, and we have quite a bit of experience with it. What Phil brings up is exactly what we’re excited about—this ability to detect these tumors at very low PSA levels. That’s the range that we’re thinking about salvage radiation in. If we do a prostatectomy and that PSA is under 1, that is really the sweet spot to consider salvage radiation therapy in. And if we’re going to do that, there’s a reassurance to know that there’s no clear metastatic disease. If we do the scan and we see metastatic disease, I’m not saying we’re not necessarily going to do that radiation, but we might think about that in context of maybe extending the field or adding in some SBRT or some other approach. So, it helps us to kind of understand how we’re going to go about that process.

The other thing that is important in this phenotype that we’re talking about, the sort of recurrent PSA rise, is the timing of that rise. If I have a patient that’s had a prostatectomy and it’s 3 or 4 years later and their PSA is inching up to 0.2, 0.25, that’s a little bit of a different scenario. Raoul, you operate on a case. When a PSA is first detectable right after surgery, say it’s 0.5 right after surgery, that’s a little bit of a different bird than that later slower rise. So, how does the scan perform, not so much just on a threshold of PSAs, but a little bit in the context of these? What I think we see is, maybe, a little bit of a different kind of clinical course of this phenotype.

Phillip Koo, MD: That’s a great point. This is why I think a lot of the studies that have been performed with imaging need to be better. Right now, a lot of these trials are single site. It’s hard to prove that what we see is actually disease or not, because many of these lesions cannot be biopsied. To this point of looking at PSA velocity, or doubling times, such as that, I think it’s clear that the biology for those cancer patients is different from the biology for other patients who are more aggressive and have a higher Gleason score at diagnosis. These are areas that I don’t think we’ve explored, in depth, as much as we should. This is probably the next step that will be involved. I think these conversations help our society and our specialty to really create better studies that bring more value to our referring physicians.

Raoul S. Concepcion, MD, FACS: Historically, looking specifically at radical prostatectomy patients, there were data that suggested considerations for ADT. This was based upon a Gleason grade of over 8 or less at the time of diagnosis, first time to biochemical recurrence being less than 3 years or greater than 3 years, and the PSA doubling time, which I think needs to be taken into consideration, more and more.
Now we also have a molecular marker, Decipher, in patients who have had a radical prostatectomy, to determine whether or not radiation therapy, especially in pathologic T3 disease, might be beneficial. Alec, do you use a lot of Decipher?

Alec Koo, MD: I don’t, principally because we have such specialization in our practice. I personally have not done a radical prostatectomy in more than 10 years. We concentrate those to our robotic surgeons. By and large, they’re the ones who we’ve been ordering Decipher for. Obviously, I’m familiar with my patients who have surgeries and who have those tests. I think the data that’s come out really point to the usefulness of the biologic markers that Decipher would demonstrate and its ability to predict recurrence and more aggressive disease down the line.

Transcript Edited for Clarity 

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Transcript:

Raoul S. Concepcion, MD, FACS: We’ve sort of alluded to some of this next-generation imaging, and we’re trying to adopt that nomenclature. In your mind, what’s out there? What’s available, especially for utilization in this particular space?

Phillip Koo, MD: First off, I love this discussion about multidisciplinary care, because that’s clearly how we can add a lot of value to our patient care. And when we talk about imaging, specifically, I think imaging is a team sport. Right now, we’re in the process of showing a success story, when it comes to imaging in a disease state that we had not had as much progress in over the past 20 years.

When it comes to imaging in the biochemical space, I think there’s been a lot of advancement, a lot of excitement, especially in the US, now that we have Axumin, which is fluciclovine, available, FDA approved, and reimbursed by the CMS (Centers for Medicare & Medicaid Services). It’s an amino acid analog that’s been shown to detect disease much sooner than any other tool that we’ve had in the past. Alec pointed out the limitations with bone scans and CTs, and we’ve had to deal with that. We’ve done a great job. But I think this is really where we take the next step.

Some of the data, with regard to fluciclovine, has shown that in one multisite trial, in the lowest quartile—PSA levels less than 0.79—detection rates were around 41%. And if we move on to Gallium-68 PSMA, there are reports of detection rates under a PSA level of 0.5 of around 40% to 50%. These are unheard of, in terms of PSA levels. I think this is extremely encouraging, and this really changes how we need to think about patients. As Neal mentioned, this idea of oligometastatic disease is going to be a bigger part of all of our practices, and we’re already seeing this. People are talking about it, and there are a lot of questions. I think it’s great that we’re having these discussions, because we need those answers.

Raoul S. Concepcion, MD, FACS: Phil, in the data that you quoted, those were for patients who have been definitively treated for their primary, but have a rising PSA. Those are not patients on androgen deprivation therapy?

Phillip Koo, MD: Correct, just elevated PSA. And currently, the label for Axumin is elevated PSA following prior therapy. So, that’s the ideal space.

Raoul S. Concepcion, MD, FACS: What is the availability of Axumin, nationwide?

Phillip Koo, MD: Currently, to my knowledge, I think there are probably over 400 sites that are offering Axumin in their PET/CT facilities. I think a lot of it is just a matter of distribution. Given the fact that Axumin is based on an F-18 isotope, it has a roughly 2-hour half-life, which allows it to be distributed pretty much all across the country. That’s what really allows it to be commercialized. A lot of us are familiar with Choline C-11. The biggest limitation with that was that the half-life was 20 minutes, which really required an onsite cyclotron facility. This puts it out of the reach of 99.9% of imaging facilities across the country.

Raoul S. Concepcion, MD, FACS: So, the real impact of these scans, essentially, is given the increased sensitivity of the scan to detect what has basically always been thought of as potentially microscopic disease, and that brings up this whole concept of oligometastatic disease. Obviously, this can potentially change therapy, whether it’s going to potentially identify a lymph node for surgery. You may find a limited distribution of bony metastases that could be amendable to potentially spot radiation, and those types of things. Besides the Axumin scan, what else, right now, is FDA approved in this particular setting?

Phillip Koo, MD: Choline C-11 is approved, but it’s approved based on facilities. The Mayo Clinic is one site where it does have FDA approval. There are other sites that will offer it, but not under FDA approval. I think the future that a lot of us are very excited about is in using Gallium-68 PSMA, which currently does not have FDA approval, but is offered, I think, in 4 sites across the country. Eventually, we foresee that being the next novel imaging tool that gets FDA approval. Hopefully, it will be paid for by our payers, as well.

Raoul S. Concepcion, MD, FACS: Dan, do you have availability of Axumin at Duke?

Daniel George, MD: We do. We’ve been doing it for probably about 9 months or so, and we have quite a bit of experience with it. What Phil brings up is exactly what we’re excited about—this ability to detect these tumors at very low PSA levels. That’s the range that we’re thinking about salvage radiation in. If we do a prostatectomy and that PSA is under 1, that is really the sweet spot to consider salvage radiation therapy in. And if we’re going to do that, there’s a reassurance to know that there’s no clear metastatic disease. If we do the scan and we see metastatic disease, I’m not saying we’re not necessarily going to do that radiation, but we might think about that in context of maybe extending the field or adding in some SBRT or some other approach. So, it helps us to kind of understand how we’re going to go about that process.

The other thing that is important in this phenotype that we’re talking about, the sort of recurrent PSA rise, is the timing of that rise. If I have a patient that’s had a prostatectomy and it’s 3 or 4 years later and their PSA is inching up to 0.2, 0.25, that’s a little bit of a different scenario. Raoul, you operate on a case. When a PSA is first detectable right after surgery, say it’s 0.5 right after surgery, that’s a little bit of a different bird than that later slower rise. So, how does the scan perform, not so much just on a threshold of PSAs, but a little bit in the context of these? What I think we see is, maybe, a little bit of a different kind of clinical course of this phenotype.

Phillip Koo, MD: That’s a great point. This is why I think a lot of the studies that have been performed with imaging need to be better. Right now, a lot of these trials are single site. It’s hard to prove that what we see is actually disease or not, because many of these lesions cannot be biopsied. To this point of looking at PSA velocity, or doubling times, such as that, I think it’s clear that the biology for those cancer patients is different from the biology for other patients who are more aggressive and have a higher Gleason score at diagnosis. These are areas that I don’t think we’ve explored, in depth, as much as we should. This is probably the next step that will be involved. I think these conversations help our society and our specialty to really create better studies that bring more value to our referring physicians.

Raoul S. Concepcion, MD, FACS: Historically, looking specifically at radical prostatectomy patients, there were data that suggested considerations for ADT. This was based upon a Gleason grade of over 8 or less at the time of diagnosis, first time to biochemical recurrence being less than 3 years or greater than 3 years, and the PSA doubling time, which I think needs to be taken into consideration, more and more.
Now we also have a molecular marker, Decipher, in patients who have had a radical prostatectomy, to determine whether or not radiation therapy, especially in pathologic T3 disease, might be beneficial. Alec, do you use a lot of Decipher?

Alec Koo, MD: I don’t, principally because we have such specialization in our practice. I personally have not done a radical prostatectomy in more than 10 years. We concentrate those to our robotic surgeons. By and large, they’re the ones who we’ve been ordering Decipher for. Obviously, I’m familiar with my patients who have surgeries and who have those tests. I think the data that’s come out really point to the usefulness of the biologic markers that Decipher would demonstrate and its ability to predict recurrence and more aggressive disease down the line.

Transcript Edited for Clarity 
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