PSMA Molecular Targeted Radiation Therapy - Andrei H. Iagaru

May 10, 2021

Detection and Localization  of Prostate Cancer: Case-based Scan Reading Review 

PSMA Molecular Targeted Radiation Therapy - Part Three of Three- Scan Reader Training and Discussions Presenter: Andrei Iagaru. 

Independent Medical Education Initiative Supported by Novartis Pharmaceutical Corporation 


Program Presenter:
Andrei H. Iagaru, MD, FACNM, Professor of Radiology - Nuclear Medicine, Chief, Division of Nuclear Medicine and Molecular Imaging, Director, Nuclear Medicine Residency Program, Co-Director, PET-MRI Research Program, Stanford University, Stanford, California

Program Discussants:
Neal Shore, MD, FACS, is the Medical Director of the Carolina Urologic Research Center. He practices with Atlantic Urology Clinics in Myrtle Beach, South Carolina

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois

Program Moderator:
Phillip J. Koo, MD, FACS Division Chief of Diagnostic Imaging at the Banner MD Anderson Cancer Center in Arizona

Read the Full Video Transcript

Phillip Koo: Welcome to UroToday. My name is Phillip Koo, and I have the pleasure of serving as a moderator for a special program titled, Detection and Localization of Prostate Cancer: Case Review Scans, Pearls and Pitfalls.

So, as we're all aware, the imaging landscape in prostate cancer has rapidly changed. Axumin fluciclovine was approved in 2016, gallium-68 PSMA-11 was approved in December 2020, and we anticipate the approval of PyL PET, hopefully in May or June 2021. And with that comes a lot of new disease states, new clinical scenarios, and new clinical dilemmas that I think oftentimes in clinical practice, we have some struggles navigating those uncharted territories. And in order to address that need, we've put together a multidisciplinary program and panel to really provide us with a comprehensive approach and perspective on how to tackle some of these questions.

And for the case review and the pearls and pitfalls, I can think of no one better than Dr. Andrei Iagaru, who is a Professor of Radiology and Chief of Nuclear Medicine at Stanford University to walk us through that. And then for our multidisciplinary panel discussion, I'm joined by my esteemed colleagues, Dr. Alicia Morgans, GU Medical Oncologist and Associate Professor at Northwestern, and Dr. Neal Shore, Urological Oncologist and Medical Director of the Carolina Research Institute in South Carolina. At this point, I'll turn it over to Andrei to get us started, and I look forward to a very stimulating discussion, so thanks Andrei for being with us.

Andrei Iagaru: All right. As Phil said, we move into the final part, the radioligand therapy, which will tie things together, hopefully. And I took the liberty of adapting this scheme from reviewing radiographics by Michael Hofman and his colleagues at Peter Mac. If you see something which is that diagnostic part, then you can treat it by substituting the imaging isotope, in this case gallium-68 or fluorine-18 with the beta emitter or alpha emitter. For beta emitter most commonly used lutetium 177. So if you see you treat it, and that's probably the best summary of what theragnostics really is. And again, anecdotal data first, I cannot emphasize enough the importance of the early work that was done by our colleagues in Germany, both on the diagnostic as well as on the therapy side. In this case, very impressive results with an alpha emitter and the imaging findings, as well as the decline in PSA.

Very, impressive. It remains to be seen if patient outcomes are as impressive as these images if we really prolong survival and improve the quality of life for these patients. And then of course other anecdotal examples here as well. But I think that really the work that was done in follow-up by Michael Hofman and his colleagues in Australia, the consortium that some of these early properly randomized studies. And I took the liberty of using the slides from the ASCO 2020. This is probably one of the best studies with results available to date and we look forward to the results of the VISION trial that I think will be presented at ASCO this year. But very interesting, the eligibility criteria for this trial, the use of both PSMA and FDG for patient selection. And this is now a classic image going from left to right again from Michael Hofman in Peter Mac, a patient that will not benefit from PSMA and the ideal patient on the right with PSMA `positive lesions and FDG negative for the same lesions.

I think that the other patient with same lesion showing up on PSMA and FDG may not have the same good outcome. We took PSMA therapy, the high FDG uptake in the same lesion syndicate, probably a very aggressive tumor with a high mechanism of DNA repair, perhaps where PSMA therapy should be used in combination, we saw this. As I mentioned, we all look forward to hearing the results of the VISION Trials is a large phase three study of Lutetium PSMA-617. And the press releases indicate positive results and we look forward to seeing those numbers. So for our discussion, when we finish, maybe we can touch upon shall we use an alpha or a beta emitter. Where do we use radioligand therapy over the long course of prostate cancer? How do we select patients? Do we need imaging, PSMA, PET alone, PSMA and FDG? How many cycles? Do we individualize those we use in dosimetry? And when do we assess response do we do a PET scan, meet cycle and of treatment, and we need other targets.

We probably won't be able to cover all of these, but before we go there, I want to show our numbers here. 2020 being an exception due to the COVID and everything that came with it. You can see that the therapy study nuclear medicine are on an accelerated curve of growth and I expect this to continue in the upcoming years. And for that reason, we convinced our institution to invest in a new space for therapies. So this is next to our scanners and I showed this in a previous presentation as a schematic, as it's shown here four private infusion rooms for therapies, two restroom space for the personnel there and across the hallway from patents back and this is now a reality.

We opened this last week and we look forward to treating patients and want to give a big shout out to my colleagues who are running these diagnostics clinics. We all participate, but we have leadership on physician, nursing, physics, radiochemistry, technologist, and clinic coordinators. I hope that it's the model that will be used more and more by others because the best way to provide patient care is to be intimately involved with these patients. You cannot just come in, push a button and leave. You have to take care of them, understand what can go wrong and be involved in their in their care together with our colleagues in medical oncology, radiation oncology, urology, et cetera. Food for thought, I could not share any cases because they're not a research protocols and I do not have that permission to share, but maybe we can have an exchange of ideas about how do we use radioligand therapy going forward.

Phillip Koo: Thank you, Andrei. You know, there's no question that radioligand therapy and therapies in general are changing the practice of nuclear medicine. And I think the specialty needs to pivot and shift in response to these trends that are changing. And, we're seeing that increase in therapies as well. And it also requires a pivot and shift in terms of comprehensive cancer programs and cancer programs across the country or world to change in how they deliver care. And I've said this before and we all, I think I've alluded to this, that nuclear medicine is the fourth pillar of a GU cancer program. And it's an absolute essential piece from the diagnostic perspective and the therapeutic perspective. And I think it's great that you guys have taken proactive steps to provide a better patient experience knowing that nuclear medicine is not just about coming in and get an imaging test. It's about coming in and getting therapies as well and spending maybe three, four, five, six hours in the nuclear medicine department.

You brought up a lot of questions and I think we could spend hours talking about this. One topic I wanted you to sort of enlighten us about is dosimetry. Right now, if we look at the other nuclear medicine therapies, it's sort of a one size fits all type of approach in terms of dosing, where do you think we're going to be headed in this with dosimetry and how can we help make this a tool or a piece to therapy that actually improves patient care?

Andrei Iagaru: So I think it's, as you said, uncharted territory. And world is pretty polarized as some people would say, you don't need it and others who say you absolutely need it. I take a little bit of the middle road approach here. I seen that there are patients who are doing dosimetry will definitely be beneficial, especially if you know that there are lesions adjacent to, by those structures that can be damaged by the radiation or for the bulk of disease. Also, I don't think that someone with oligometastatic disease where you may want to do radioligand therapy and maybe PET-guided radiation therapy should get the same dosage as someone who has widespread disease. Why should we use the same unit, right? I think that there are instances where we need to do personalized as imagery and other indications say, what if you can give the same total dose over two cycles, as opposed to six cycles, right?

Would that not be beneficial for the patient to only have to come twice instead of six times to the hospital? So if you want to do that higher activity delivered in less fractions, let's say to use a term from external radiation, then you will need to have some dosimetry information. I think for majority of patients probably not needed, but we need to, to know how to do it. And we need to have frankly, scientifically based criteria for when to do those imagery and went to not. We don't complicate things for the sake of more scans or more numbers. We want to do it when they have an impact on outcomes.

Phillip Koo: Great. Thank you. So, Alicia, what are your thoughts on radioligand therapies, especially now that we, we know that VISION had met its endpoint, where do you think we're headed and how do you think we can maximize the value or expedite the sort of incorporation of RLT into a treatment?

Alicia Morgans: So I'm really enthusiastic, very excited about these therapies. I'm always happy to have new approvals for prostate cancer, and I expect we'll have some in the near future. And I also am always excited to see the way that this particular avenue for treatment may continue to expand, because maybe we'll have Lutetium now maybe we'll have others in the future.

Things like actinium or we saw that the paper. And so I think that we can continue to expand our targeted radiopharmaceuticals and continue to really bring our nuclear medicine folks into the fold, even further to have them participate in discussions and in our multi disciplinary tumor boards. Where we talk about is this the right time for this particular approach? Or should we wait, should we do it early? Should we do it late? And as we continue to understand the side effects of the longer term side effects of these therapies, that will inform those decisions as well. So I think we're really at the cusp of having options like these for our patients, but there's so much more to learn, which is incredibly exciting. And I look forward to seeing this area continue to evolve.

Phillip Koo: Great. So Neal you've had experience with visiting multiple different practices across the country, across the world. Obviously access is going to be a major issue when it comes to radioligand therapies and delivery of that type of care. And there are multiple models. What are your thoughts on how we, what the care model delivery should look like when it comes to these types of therapies?

Neal Shore: If you have the ability to have true efficient multidisciplinary interaction, that's really paralleling our tier one academic models. That should be the goal within the community. Nuclear medicine radiologist dialoguing with uro-oncologist, medical oncologist, radiation oncologist, or pathologist or interventional radiologists. And we're getting better.

One of the silver linings of COVID has been the ability to do virtual meetings. It used to be that while we, it was just the geographical barriers sometimes just with, even within a large building, but now there's an opportunity to get virtual meetings on a screen, and there's even an ability to get appropriately compensated for it. And that varies depending upon your healthcare model. I will say that we were really proud to be part of the VISION trial as a urology community site. We enrolled 10 patients, and I believe we were the largest accruing urology community site globally.

And we had great success in doing it by partnering with our radiation oncologists and getting their appropriate radioactivities materials license. So there are a lot of different moving pieces here going forward, but it should not be daunting. Prostate cancer, as in all GU oncology and most cancers are becoming more specialized and more complex. And I think for our Uro-oncology colleagues and medical oncology colleagues in the community, the importance of subspecialization and aggregating the talent and the education is absolutely pivotal and essential to quality care wherever you are in the world. And it's up to us to figure out how to best do this and through papers and studies. And one of the things that Andrei you showed, and I know this is very different in Australia and the way Michael Hofman, and they get regular FDG PET and PSMA PET. I don't know how practical that will be in the U.S. From a cost standpoint.

And that's a very, just simple but practical aspect. And that certainly wasn't a requirement in the VISION trial. Your slide that had all those questions on it, I thought was fantastic because those are the research positions that have to be answered. Why are there some outstanding, excellent responders just after a couple of treatments who just go on and respond for durations of period. And then there are those who were resistant and despite positive scanning who don't always respond. And why is that? I think the multidisciplinary approach, Phil, is the only way we're going to answer this and getting more quality trials up and going.

Phillip Koo: Great. Thank you. And I agree. I think this is the beginning of something very exciting and look forward to more developments here. I think today's discussion has been amazing. I learned a lot personally through all these comments and discussions, wanted to turn it go around the group for any final comments or thoughts about anything you'd like to discuss as we close this great program. So maybe I'll start with you Alicia, and then go to Neal and then let Andrei close us out.

Alicia Morgans: Great. Thank you. And thank you all. This really has been a fabulous discussion. I always learned from these kinds of things. And I think that really is my message to all of us, as we move forward, we will continue to learn. And as I said, I look forward to understanding how to best integrate the therapies, the imaging into our practices. I also look forward to understanding how we pair imaging with biology, how we use circulating tumor DNA, perhaps, or other biomarkers to help us understand what's the best imaging strategy for this patient, and how should we use imaging to really compliment what we can do in terms of molecular biology to improve not only our visualization, but our treatment approach, and really at the end of the day, just match the right patient with the right treatment and hopefully get the best outcome. So this is such an integral part of that puzzle, and I continue to look forward to the future.

Neal Shore: Well, thank you very much, Phil, for moderating great sessions as always, and Andrei, awesome cases and great presentation and materials. So thank you for that. I agree with what Alicia said. It's how do we optimize our diagnostic markers, both lab based and our imaging. Imaging is extremely important and imaging is now becoming a front and center as to how we coordinate with our markers and think about optimal initial therapy to sequencing. You know, VISION is, will almost certainly result in approval in post-chemotherapy mCRPC patients, which is the schema and the inclusion criteria.

But we're all aware now there are multiple studies being done in MCRPC pre-chemotherapy and studies now starting with theragnostics and mCSPC. So our colleagues need to be aware of that. We need to enroll those trials as quickly as possible, thinking about whether it's an alpha or beta emitter or potential alpha emitter or beta emitter with a small ligand molecule combination strategies, really exciting time as we continue to pursue this, this goal of not having patients die of advanced prostate cancer. So I think it's a wonderful time to be involved in this research and, and offering patients additional hope.

Andrei Iagaru: Thank you all for the invitation to partner with you for this session. I too, learned a lot. I very much enjoyed it. Phil, excellent job moderating. And most importantly, thank you all for the partnership. I am sure that only by working together, we can advance the patient care for prostate cancer and other entities. And I'm proud to be a part of a multidisciplinary team including here.

Phillip Koo: Great. Thank you.

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