Selected Podcast
Advanced Imaging for Prostate Cancer
Wayne Brisbane, MD, discusses advanced imaging for prostate cancer. He evaluates the currently available imaging modalities. He defines the best use for each modality and he discusses future directions for imaging in prostate cancer.
Featuring:
Learn more about Wayne Brisbane, MD
Wayne Brisbane, MD
Wayne Brisbane, MD, is an assistant professor of medicine in the Department of Urology at the University of Florida College of Medicine.Learn more about Wayne Brisbane, MD
Transcription:
Melanie Cole: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to join us as we explore advanced imaging for prostate cancer. Joining me is Dr. Wayne Brisbane. He's an Assistant Professor in the Department of Urology at the University of Florida College of Medicine. Dr. Brisbane also practices at UF Health Shands Hospital in Gainesville, Florida. Dr. Brisbane, it's a pleasure to have you join us again. I'd like you to start by telling us how advances in radiologic imaging have really augmented your diagnostic and therapeutic capabilities for men with prostate cancer. Any that you want to mention that have really been game changers?
Dr. Wayne Brisbane: Thanks again, Melanie, for having me on. Yeah, there's been a real renaissance in prostate cancer imaging over the last 10 years, but even more in the last two years. And so for many decades, the only imaging modalities we had for diagnosing prostate cancer and imaging prostate cancer were ultrasound, CT and bone scan. So traditionally, men who had an elevated PSA, they'd get an ultrasound-guided biopsy. That ultrasound-guided biopsy would show us the anatomy of the prostate, but couldn't delineate between cancer and benign. And then if cancer was diagnosed, they would sometimes get a CT scan and a bone scan to see if the cancer had spread anywhere in the body. And that paradigm has rapidly shifted.
So currently, we have MRI, so MRI is a multi-parametric MRI, it has multiple phases, that's the multiple parametric portion of it. And the important study that our listeners need to know about is the PROMISE study. This was around 700 men who got an MRI and then were followed by a mapping biopsy. This is about as close as you can get to a prostatectomy and understanding exactly where the tissue is. They also got a TRUS, like a regular templated 12-core biopsy. And in that study, they showed that MRI can triage men showing that, you know, men with a negative MRI, it's a pretty good finding for not having cancer. So that is one thing that's now been incorporated into multiple guidelines. So the NCCN guidelines, it's important for people to know February of 2021 have changed. So now men with a PSA greater than 3 have an indication for an MRI and consideration of biomarkers. And there's multiple biomarkers that are available, the prostate health index, SelectMDx, 4K, ExoDx test. So there's no designation in which one needs to be used, but just using PSA is probably something that's a little antiquated.
The other tests that I think people should be aware of that is absolutely going to change the landscape is a PSMA PET scan. So PSMA PET scans, if there's a protein surface, it's like I guess an enzyme that is overexpressed in prostate cancer and there is a PET radiotracer that binds to this. And there's multiple different ways that companies are using it, but the current one that's commercially available is called DCFPyL, but the easiest way to think about it is just PSMA PET scan. And that has two new indications, both for patients who have biochemical recurrence. So they've been treated and then have a recurrence of disease, common after like a radiation recurrence. So you can find where the cancer is lighting up post-treatment. The other indication, which is a little new, is replacing that CT and bone scan that we usually did for staging, so especially men in high-risk disease or unfavorable intermediate risk disease can get these PSMA scans to see if cancer has spread anywhere else. And so those are two new trials.
The CONDOR trial was the one looking at-- both came out of Australia, looking at men with biochemical recurrence and then the OSPREY trial was looking at the staging in high risk disease. So the final imaging modality that I want to make sure people are aware of that is very new, probably the newest out of all three modalities we're talking about is microultrasound. This is a high-frequency ultrasound that evaluates the prostate. It's only looking at the prostate. It doesn't look at anything else. But it does a very nice job of delineating where tumors are versus where is benign tissue. And so this is the first time where ultrasound's been able to delineate cancer versus benign tissue, and it looks to be very, you know, very accurate. There's definitely some shortfalls in using ultrasound, but it's important that there's this trial that's ongoing called the OPTIMUM study that's going to compare MRI versus microultrasound to identify a prostate cancer on biopsy. So we're going to wait for the trial results to read out.
But three brand new imaging modalities, MRI, which is on guidelines and has been around for, I would say, five to ten years and has really come into its own. And that is, like I said to people with elevated PSA, it's on multiple guidelines, both the NCCN, AUA and I think it's Abdominal Radiology Society recommend using that as a preliminary test and to guide biopsy. PSMA is now on guidelines and just was starting to get approved. And that's for men who have high risk disease prior to treatment and then men with biochemical failure or biochemical recurrence post-treatment and then a brand new ultrasound imaging modality, which is to localize a prostate cancer probably will have some implications for staging of prostate cancer and definitely will be useful for guiding needle biopsies, and that's microultrasound, which will be studied through the OPTIMUM trial, which is currently enrolling.
Melanie Cole: How are you deciding which one of these to use? And what an exciting time in your field, Dr. Brisbane. Really so many things are constantly evolving. And while you're telling us a little bit more, to expand just a little bit more on patient selection for providers that really are looking to use these, how might some of them help to triage men to help patients avoid biopsies and other procedural interventions that could cause side effects?
Dr. Wayne Brisbane: Yeah. So just to give a practical example, so somebody who comes into my clinic who has an elevated PSA, my cut point is going to be 3, which is a little bit lower than what has been kind of traditional. So, basically, I'm starting the screening between 45 and 75 for average risk men and then between 40 and 75 for men of African ancestry, especially if there's, you know, a family history, germline mutations in the family or strong family history. If the PSA is less than 1, kind of screening them between two to four-year intervals. If the PSA's between 1 and 3, I'm screening them at one to two-year intervals. But if the PSA is greater than 3, then I'm going to multiparametric MRI and consideration of a biomarker and I'm using urinary biomarkers, but I don't have a strong preference. There's a lot of really good ones that are out there.
If there's something that's positive on the MRI, so that's a PI-RADS 3 or above, and those PI-RADS are just the risk score that the MRI gets. If the PI-RADS score is 3 or above, we're biopsying that, and I'm using a combination of MRI and microultrasound to guide the biopsy needle. I think it's a very accurate way of going about it. If it is a negative MRI and the PSA density is less than 0.15, that PSA density is important because big prostates produce a lot of PSA. And so as long as if you can evaluate, is it a big prostate that's producing the PSA by dividing their PSA by the prostate volume, you can normalize the PSA values that you're getting and then you can see if the PSA density is less than 0.15 and a negative MRI, that's very protective. Some men who are nervous, I'll offer them a biomarker in addition to that, but that's probably overkill. But regardless, using those MRI plus biomarkers after repeating the PSA to confirm that it's above 3, just trying to decide do men need the biopsy?
And then once imaging has confirmed cancer, let's say it's a high-risk cancer, then I'm using PSMA to stage them rather than a CT and bone scan. And that gives a very accurate assessment of where the cancer is. Is the man going to benefit from local therapy with surgery or radiation? And then God forbid that they fail their primary treatment, we're using PSMA again to see where the cancer may be outside of the prostate.
Melanie Cole: So, where do you see this going as it's evolving just so much and pretty rapidly and our population is growing ever older, so men are living longer? Where do you see some future directions for imaging in prostate cancer? What's new on the horizon that you're looking forward to?
Dr. Wayne Brisbane: Yeah. I think a lot of treatments, especially in localized disease, but also in metastatic disease are going to be altered by our ability to see cancer better. So within the localized disease set, you're going to be able to see where tumors are and where tumors are not using technologies like MRI and microultrasound, and that has several implications. For people undergoing surgery, we're able to tailor the surgery with less damage to the adjacent critical structures, like the neurovascular bundle, the bladder neck, the external sphincter, so that results in surgery with less damage to surrounding tissue and then less side effects.
The same thing goes with radiation. They're able to boost the radiation dose to the actual tumor because they can see where it is next to the benign tissue. And so the recent readout of the FLAME trial where that was done showed that there is an improvement if you boost the actual tumor rather than just giving the same dose to the whole prostate. And that makes sense. And I think with time, we'll actually see that we're able to even reduce the radiation effects to other areas that cause a lot of side effects. So I'm hoping that we'll have more targeted treatment. There's definitely some push also just to treat the tumor as the only thing. So treating the tumor with something called focal therapy, there's multiple different energy sources that have been used, but that's a kind of an extension of what I'm talking about, where you're able to visualize where the tumor is, you treat just the tumor and leave the surrounding structures untreated. There's a long way to go. And I think that there's a lot of research yet to do before we can just get away with treating the tumor in a margin. But I think that it's a very exciting time to be working in prostate cancer.
and then the other flip thing that's very interesting is for many years, we use CT and bone scan to stage people. So we would kind of decide on what their treatments should be initially based on their burden of disease. But PSMA is really going to shift how well we can see a burden of disease. And so we'll kind of rewrite the book as far as how much burden of disease equals what treatments. For example, CT and bone scan used to miss men with small amounts of metastasis. So we're going to start finding men with this period of oligometastatic or a small amount of metastatic disease. And so we kind of have to figure out exactly how to best treat them. So I think it'll be very interesting.
The final thing that I'll say is that some people are also working on taking the PSMA, the linkage, and attaching it to a radioemitter, so like an alpha or beta emitter. And so there's a whole new group of treatments called radiopharmaceuticals that are opening up. And that's going to be in men currently with castration-resistant disease. But I think it'll probably move forward in the metastatic disease space.
Melanie Cole: Wow. So informative, Dr. Brisbane. What a great guest you are. And I hope that you'll join us again to keep updating us as these things evolve. As we said, this is happening pretty rapidly, and there's many exciting advancements in imaging for prostate cancer. Thank you so much.
To refer your patient to Dr. Wayne Brisbane or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please always remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole.
Melanie Cole: Welcome to UF Health MedEd Cast with UF Health Shands Hospital. I'm Melanie Cole, and I invite you to join us as we explore advanced imaging for prostate cancer. Joining me is Dr. Wayne Brisbane. He's an Assistant Professor in the Department of Urology at the University of Florida College of Medicine. Dr. Brisbane also practices at UF Health Shands Hospital in Gainesville, Florida. Dr. Brisbane, it's a pleasure to have you join us again. I'd like you to start by telling us how advances in radiologic imaging have really augmented your diagnostic and therapeutic capabilities for men with prostate cancer. Any that you want to mention that have really been game changers?
Dr. Wayne Brisbane: Thanks again, Melanie, for having me on. Yeah, there's been a real renaissance in prostate cancer imaging over the last 10 years, but even more in the last two years. And so for many decades, the only imaging modalities we had for diagnosing prostate cancer and imaging prostate cancer were ultrasound, CT and bone scan. So traditionally, men who had an elevated PSA, they'd get an ultrasound-guided biopsy. That ultrasound-guided biopsy would show us the anatomy of the prostate, but couldn't delineate between cancer and benign. And then if cancer was diagnosed, they would sometimes get a CT scan and a bone scan to see if the cancer had spread anywhere in the body. And that paradigm has rapidly shifted.
So currently, we have MRI, so MRI is a multi-parametric MRI, it has multiple phases, that's the multiple parametric portion of it. And the important study that our listeners need to know about is the PROMISE study. This was around 700 men who got an MRI and then were followed by a mapping biopsy. This is about as close as you can get to a prostatectomy and understanding exactly where the tissue is. They also got a TRUS, like a regular templated 12-core biopsy. And in that study, they showed that MRI can triage men showing that, you know, men with a negative MRI, it's a pretty good finding for not having cancer. So that is one thing that's now been incorporated into multiple guidelines. So the NCCN guidelines, it's important for people to know February of 2021 have changed. So now men with a PSA greater than 3 have an indication for an MRI and consideration of biomarkers. And there's multiple biomarkers that are available, the prostate health index, SelectMDx, 4K, ExoDx test. So there's no designation in which one needs to be used, but just using PSA is probably something that's a little antiquated.
The other tests that I think people should be aware of that is absolutely going to change the landscape is a PSMA PET scan. So PSMA PET scans, if there's a protein surface, it's like I guess an enzyme that is overexpressed in prostate cancer and there is a PET radiotracer that binds to this. And there's multiple different ways that companies are using it, but the current one that's commercially available is called DCFPyL, but the easiest way to think about it is just PSMA PET scan. And that has two new indications, both for patients who have biochemical recurrence. So they've been treated and then have a recurrence of disease, common after like a radiation recurrence. So you can find where the cancer is lighting up post-treatment. The other indication, which is a little new, is replacing that CT and bone scan that we usually did for staging, so especially men in high-risk disease or unfavorable intermediate risk disease can get these PSMA scans to see if cancer has spread anywhere else. And so those are two new trials.
The CONDOR trial was the one looking at-- both came out of Australia, looking at men with biochemical recurrence and then the OSPREY trial was looking at the staging in high risk disease. So the final imaging modality that I want to make sure people are aware of that is very new, probably the newest out of all three modalities we're talking about is microultrasound. This is a high-frequency ultrasound that evaluates the prostate. It's only looking at the prostate. It doesn't look at anything else. But it does a very nice job of delineating where tumors are versus where is benign tissue. And so this is the first time where ultrasound's been able to delineate cancer versus benign tissue, and it looks to be very, you know, very accurate. There's definitely some shortfalls in using ultrasound, but it's important that there's this trial that's ongoing called the OPTIMUM study that's going to compare MRI versus microultrasound to identify a prostate cancer on biopsy. So we're going to wait for the trial results to read out.
But three brand new imaging modalities, MRI, which is on guidelines and has been around for, I would say, five to ten years and has really come into its own. And that is, like I said to people with elevated PSA, it's on multiple guidelines, both the NCCN, AUA and I think it's Abdominal Radiology Society recommend using that as a preliminary test and to guide biopsy. PSMA is now on guidelines and just was starting to get approved. And that's for men who have high risk disease prior to treatment and then men with biochemical failure or biochemical recurrence post-treatment and then a brand new ultrasound imaging modality, which is to localize a prostate cancer probably will have some implications for staging of prostate cancer and definitely will be useful for guiding needle biopsies, and that's microultrasound, which will be studied through the OPTIMUM trial, which is currently enrolling.
Melanie Cole: How are you deciding which one of these to use? And what an exciting time in your field, Dr. Brisbane. Really so many things are constantly evolving. And while you're telling us a little bit more, to expand just a little bit more on patient selection for providers that really are looking to use these, how might some of them help to triage men to help patients avoid biopsies and other procedural interventions that could cause side effects?
Dr. Wayne Brisbane: Yeah. So just to give a practical example, so somebody who comes into my clinic who has an elevated PSA, my cut point is going to be 3, which is a little bit lower than what has been kind of traditional. So, basically, I'm starting the screening between 45 and 75 for average risk men and then between 40 and 75 for men of African ancestry, especially if there's, you know, a family history, germline mutations in the family or strong family history. If the PSA is less than 1, kind of screening them between two to four-year intervals. If the PSA's between 1 and 3, I'm screening them at one to two-year intervals. But if the PSA is greater than 3, then I'm going to multiparametric MRI and consideration of a biomarker and I'm using urinary biomarkers, but I don't have a strong preference. There's a lot of really good ones that are out there.
If there's something that's positive on the MRI, so that's a PI-RADS 3 or above, and those PI-RADS are just the risk score that the MRI gets. If the PI-RADS score is 3 or above, we're biopsying that, and I'm using a combination of MRI and microultrasound to guide the biopsy needle. I think it's a very accurate way of going about it. If it is a negative MRI and the PSA density is less than 0.15, that PSA density is important because big prostates produce a lot of PSA. And so as long as if you can evaluate, is it a big prostate that's producing the PSA by dividing their PSA by the prostate volume, you can normalize the PSA values that you're getting and then you can see if the PSA density is less than 0.15 and a negative MRI, that's very protective. Some men who are nervous, I'll offer them a biomarker in addition to that, but that's probably overkill. But regardless, using those MRI plus biomarkers after repeating the PSA to confirm that it's above 3, just trying to decide do men need the biopsy?
And then once imaging has confirmed cancer, let's say it's a high-risk cancer, then I'm using PSMA to stage them rather than a CT and bone scan. And that gives a very accurate assessment of where the cancer is. Is the man going to benefit from local therapy with surgery or radiation? And then God forbid that they fail their primary treatment, we're using PSMA again to see where the cancer may be outside of the prostate.
Melanie Cole: So, where do you see this going as it's evolving just so much and pretty rapidly and our population is growing ever older, so men are living longer? Where do you see some future directions for imaging in prostate cancer? What's new on the horizon that you're looking forward to?
Dr. Wayne Brisbane: Yeah. I think a lot of treatments, especially in localized disease, but also in metastatic disease are going to be altered by our ability to see cancer better. So within the localized disease set, you're going to be able to see where tumors are and where tumors are not using technologies like MRI and microultrasound, and that has several implications. For people undergoing surgery, we're able to tailor the surgery with less damage to the adjacent critical structures, like the neurovascular bundle, the bladder neck, the external sphincter, so that results in surgery with less damage to surrounding tissue and then less side effects.
The same thing goes with radiation. They're able to boost the radiation dose to the actual tumor because they can see where it is next to the benign tissue. And so the recent readout of the FLAME trial where that was done showed that there is an improvement if you boost the actual tumor rather than just giving the same dose to the whole prostate. And that makes sense. And I think with time, we'll actually see that we're able to even reduce the radiation effects to other areas that cause a lot of side effects. So I'm hoping that we'll have more targeted treatment. There's definitely some push also just to treat the tumor as the only thing. So treating the tumor with something called focal therapy, there's multiple different energy sources that have been used, but that's a kind of an extension of what I'm talking about, where you're able to visualize where the tumor is, you treat just the tumor and leave the surrounding structures untreated. There's a long way to go. And I think that there's a lot of research yet to do before we can just get away with treating the tumor in a margin. But I think that it's a very exciting time to be working in prostate cancer.
and then the other flip thing that's very interesting is for many years, we use CT and bone scan to stage people. So we would kind of decide on what their treatments should be initially based on their burden of disease. But PSMA is really going to shift how well we can see a burden of disease. And so we'll kind of rewrite the book as far as how much burden of disease equals what treatments. For example, CT and bone scan used to miss men with small amounts of metastasis. So we're going to start finding men with this period of oligometastatic or a small amount of metastatic disease. And so we kind of have to figure out exactly how to best treat them. So I think it'll be very interesting.
The final thing that I'll say is that some people are also working on taking the PSMA, the linkage, and attaching it to a radioemitter, so like an alpha or beta emitter. And so there's a whole new group of treatments called radiopharmaceuticals that are opening up. And that's going to be in men currently with castration-resistant disease. But I think it'll probably move forward in the metastatic disease space.
Melanie Cole: Wow. So informative, Dr. Brisbane. What a great guest you are. And I hope that you'll join us again to keep updating us as these things evolve. As we said, this is happening pretty rapidly, and there's many exciting advancements in imaging for prostate cancer. Thank you so much.
To refer your patient to Dr. Wayne Brisbane or to listen to more podcasts from our experts, please visit ufhealth.org/medmatters. That concludes today's episode of UF Health MedEd Cast with UF Health Shands Hospital. Please always remember to subscribe, rate and review this podcast and all the other UF Health Shands Hospital podcasts. I'm Melanie Cole.