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Advanced Imaging Techniques for Prostate Cancer

Panelists: Raoul S. Concepcion, MD, FACS, The Comprehensive Prostate Center; Jorge A. Garcia, MD, FACP, Taussig Cancer Institute; Alicia K. Morgans, MD, MPH, Vanderbilt University Medical Center; Ashley E. Ross, MD, PhD, Johns Hopkins Medical Institution; Daniel R. Saltzstein, MD, Urology San Antonio
Published Online: Tuesday, Dec 06, 2016



Transcript:

Alicia K. Morgans, MD, MPH:
My hope is that imaging, and other technologies to identify those most aggressive patients, will be here shortly, and we’ll be able to integrate that into care.

Raoul S. Concepcion, MD: Speaking of imaging, Ash, tell us your experience, now, with some of the newer techniques, specifically as we concentrate our imaging efforts right now on the patients in the CRPC (castration-resistant prostate cancer) setting. But, your institution has done some trials looking at advanced imaging techniques even in this hormone-naïve setting, early setting. Update us, a little bit.

Ashley E. Ross, MD, PhD: I think there has been a lot of progress in this field, and it’s coming more and more to the national availability for a lot of providers. Some of what you’re referring to was derived from Marty Pomper’s work. He was looking at prostate-specific membrane antigen and he found that small urea-based molecules could be have a high affinity for them, and labeled them. There’s an F18- labeled version that some people refer to as the DCPYL. There’s another gadolinium-labeled version that’s been used a lot in Australia and Europe, and now, is in the US, as well. We’ve been looking mainly at the F18-labeled versions at our institution, and we’ve done a couple trials that I think have been quite remarkable. These are pilot-level studies and then clinical utility studies, but one was a trial of patients after definitive treatment who had biochemical recurrence. We wanted to see, if we imaged them at low PSAs, below 1, how many times would we see a lesion? And then, we would treat them with whatever type of therapy we wanted and reimage them to get a proxy of it actually being a true positive or a true negative.

Raoul S. Concepcion, MD: In all those patients, had they had preoperative scans, traditional bone scans that were negative?

Ashley E. Ross, MD, PhD: Yes, preoperative traditional scans that were negative. To bring up Dr. Garcia’s point, too, what we found first was 70% of the patients—and I was a little bit shocked—would have some kind of detectable lesion usually in a lymph node, although some bone lesions were seen. To your point, we also did another trial where we took high-risk patients, NCCN high risk or very high risk, preoperatively, and scanned them before surgery. About 10% of those patients would even have M1a prostate cancer prior to surgery. And so, what it tells us is two things. In the biochemical recurrent setting, what you are looking for after definitive “treatment” is, is your recurrence localized or not? I truly believe there’s a difference, even in the man who has “metastatic disease,” are they really metastatic or just N1 with pelvic nodes versus M1a? And there’s certainly a difference between M1a and M1b, as well, and the imaging is really going to show us that. The secondary question, or part of it, is we’ve talked about identifying which men you need to treat, but I think we have to move towards looking at treatment that are really cytotoxic or ablative. And we’re going to talk, maybe later in the session, about some of the bone-directed therapies, etc. But, also with stereotactic radiation, we can start to spot these lesions well. We don’t really have great evidence that that’s going to make a difference, whether treating a micrometastasis that’s really micrometastasis in the blood is different than treating a colony of metastatic cells that are sitting in a bone or on a lymph node in a microenvironment is [going to make a difference] there. But, I agree with you. The FDA’s approved the Blue Earth compound, which is mainly an Emory-developed compound, that’s right now in clinical utility trials. These are PET PSMA-based (prostate-specific membrane antigen-based) molecules. They appear to be more sensitive than even choline, probably around the same sensitivity, in my impression, for bone as fluoride. [They are] more specific than those compounds, and they will start to revolutionize our ability to detect what’s going on. And, I don’t know whether that’s going to change outcomes for the patients, or not yet.

Raoul S. Concepcion, MD: I completely agree that the new imaging techniques are going to be widely used, but it’s going to create a lot of questions because they could be so sensitive. What’s the clinical meaning of all that, especially, because many of these patients probably would have traditionally had negative bone scan CTs? Now, we’re talking about in terms of staging, potentially identifying patients, which, I think, we all are moving towards, and the therapeutic management of oligometastatic disease, and how to manage the primary.

Transcript Edited for Clarity

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Transcript:

Alicia K. Morgans, MD, MPH:
My hope is that imaging, and other technologies to identify those most aggressive patients, will be here shortly, and we’ll be able to integrate that into care.

Raoul S. Concepcion, MD: Speaking of imaging, Ash, tell us your experience, now, with some of the newer techniques, specifically as we concentrate our imaging efforts right now on the patients in the CRPC (castration-resistant prostate cancer) setting. But, your institution has done some trials looking at advanced imaging techniques even in this hormone-naïve setting, early setting. Update us, a little bit.

Ashley E. Ross, MD, PhD: I think there has been a lot of progress in this field, and it’s coming more and more to the national availability for a lot of providers. Some of what you’re referring to was derived from Marty Pomper’s work. He was looking at prostate-specific membrane antigen and he found that small urea-based molecules could be have a high affinity for them, and labeled them. There’s an F18- labeled version that some people refer to as the DCPYL. There’s another gadolinium-labeled version that’s been used a lot in Australia and Europe, and now, is in the US, as well. We’ve been looking mainly at the F18-labeled versions at our institution, and we’ve done a couple trials that I think have been quite remarkable. These are pilot-level studies and then clinical utility studies, but one was a trial of patients after definitive treatment who had biochemical recurrence. We wanted to see, if we imaged them at low PSAs, below 1, how many times would we see a lesion? And then, we would treat them with whatever type of therapy we wanted and reimage them to get a proxy of it actually being a true positive or a true negative.

Raoul S. Concepcion, MD: In all those patients, had they had preoperative scans, traditional bone scans that were negative?

Ashley E. Ross, MD, PhD: Yes, preoperative traditional scans that were negative. To bring up Dr. Garcia’s point, too, what we found first was 70% of the patients—and I was a little bit shocked—would have some kind of detectable lesion usually in a lymph node, although some bone lesions were seen. To your point, we also did another trial where we took high-risk patients, NCCN high risk or very high risk, preoperatively, and scanned them before surgery. About 10% of those patients would even have M1a prostate cancer prior to surgery. And so, what it tells us is two things. In the biochemical recurrent setting, what you are looking for after definitive “treatment” is, is your recurrence localized or not? I truly believe there’s a difference, even in the man who has “metastatic disease,” are they really metastatic or just N1 with pelvic nodes versus M1a? And there’s certainly a difference between M1a and M1b, as well, and the imaging is really going to show us that. The secondary question, or part of it, is we’ve talked about identifying which men you need to treat, but I think we have to move towards looking at treatment that are really cytotoxic or ablative. And we’re going to talk, maybe later in the session, about some of the bone-directed therapies, etc. But, also with stereotactic radiation, we can start to spot these lesions well. We don’t really have great evidence that that’s going to make a difference, whether treating a micrometastasis that’s really micrometastasis in the blood is different than treating a colony of metastatic cells that are sitting in a bone or on a lymph node in a microenvironment is [going to make a difference] there. But, I agree with you. The FDA’s approved the Blue Earth compound, which is mainly an Emory-developed compound, that’s right now in clinical utility trials. These are PET PSMA-based (prostate-specific membrane antigen-based) molecules. They appear to be more sensitive than even choline, probably around the same sensitivity, in my impression, for bone as fluoride. [They are] more specific than those compounds, and they will start to revolutionize our ability to detect what’s going on. And, I don’t know whether that’s going to change outcomes for the patients, or not yet.

Raoul S. Concepcion, MD: I completely agree that the new imaging techniques are going to be widely used, but it’s going to create a lot of questions because they could be so sensitive. What’s the clinical meaning of all that, especially, because many of these patients probably would have traditionally had negative bone scan CTs? Now, we’re talking about in terms of staging, potentially identifying patients, which, I think, we all are moving towards, and the therapeutic management of oligometastatic disease, and how to manage the primary.

Transcript Edited for Clarity
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