Implications of PSMA PET Imaging for Prostate Cancer Presentation & Discussion - Oliver Sartor

January 13, 2021

A Step Towards Personalized Medicine: PSMA PET Imaging in Prostate Cancer

Implications of PSMA PET Imaging for Prostate Cancer Presentation & Discussion - Oliver Sartor

Independent Medical Education Initiative Supported by Progenics Pharmaceuticals, Inc. a subsidiary of Lantheus Holdings, Inc.



Biographies:

Presenter:
A. Oliver Sartor, MD Professor of Medicine and Medical Director, Tulane Cancer Center; C. E. and Bernadine Laborde Professor of Cancer Research

Moderators:
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

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

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.

Related Content:

View Complete Educational Program: A Step Towards Personalized Medicine: PSMA-PET Imaging in Prostate Cancer


Read the Full Video Transcript

Neal Shore: Welcome everyone to implementation for "A Step Towards Personalized Medicine, PET-PSMA Imaging in Prostate Cancer". This is one of a multi-part series. I'm Neal Shore, the Medical Director of Carolina Urologic Research Center, and it's a great privilege for me to introduce our speaker for this program today. My good friend and colleague, Dr. Oliver Sartor. Oliver is the CE and Bernadine Laborde Professor of Cancer Research, Professor of Medicine, and Medical Director at Tulane Cancer Center in New Orleans. And he is going to address today evaluating treatment assessments and changes, metastasis directed therapy for oligometastatic disease, treatment decisions based upon scans for early disease, specifically, look at the OSPREY trial. Phase II randomized observation versus stereotactic ablative radiation for oligometastatic prostate cancer, the ORIOLE trial. So with that, thank you so much, Oliver, for joining us and please take it away.

Oliver Sartor: Great. Thank you very much, Neal, and really a privilege to be here today with you guys. Love these programs and we always have not only good discussions, but I think derive some new insights about how we approach patients before we get this program over with. I'm going to be talking today about PET and prostate cancer and some updates, and the real implications about the imaging that we do today and the imaging we're going to be doing tomorrow. So it really is interesting to be able to look at these changes. So I'm going to start off talking, just sort of generally about PET imaging and how it improves detection of prostate cancer. And we've got a variety of images now, but I think everything is changing and that's what's important. The PSMA PET, the gallium 68 PSMA-11 is now approved at UCLA and UCSF, and the US FDA application was accepted from Telix on November 24th, 2020.

In addition, the 18F DCFPyl PET now has an FDA PDUFA date. It's been given priority review and there will be a decision by May 28, 2021. That is exciting. In addition, we've had choline PET approved at Mayo for a number of years. Fluciclovine 18F has been FDA approved. It's less sensitive than PSMA. There's FDG PET, which is the 18F, but it's not approved in prostate cancer. And then for bone only stromal reactions, there's sodium fluoride PET. So let's begin to look at the radionuclides, just for imaging in general, which I briefly wanted to cover. We have the gamma emitters of photons and then the positrons. And I've already mentioned C-11 or C-11 choline and gallium 68, which is part of the PSMA-11 imaging agent, 18F, which is not only used in the DCFPyL, but also sodium chloride.

And there are also some new ones coming like copper-64 and zirconium-89. So keep your eyes out for these new isotopes. They're going to be coming into the clinics in the very, very near future. And I think that the critical role for imaging in any world-class therapy is, well, recognize many local therapy failures are simply secondary to poor understanding of a disease localization. If you treat a radical prostatectomy and the patient has already had metastatic disease, well, guess what, it's not going to work. We have a whole series now of investigations, and I'll be covering one of these a little bit later today in the OSPREY trial for these prostate-directed therapies and how we began to look at higher risk disease and how we began to think about better risk stratification.

I'll be a little bit conjectural, but I think this is my opinion anyway. I think PSMA PET is likely anywhere from 10 to a 100 times better than conventional imaging, but no imaging will ever be perfect. You simply cannot detect a small, small cluster of cells. Nevertheless, this is the best imaging that we've ever seen. We have the ability for molecular imaging to redefine both localized and oligometastatic disease. I'm going to initially be talking a little bit about oligometastatic disease. And this is the type of disease that you are able to detect in only a few sites and a little bit of debate over how many sites ought to be considered oligometastatic; One, two, three, four, five? There's no clear cut answer to that, but typically three and lower is something that almost everyone would consider to be oligometastatic.

Now, one of the things that has been shown, and this was really an elegant study by Steve Bova and colleagues, is that prostate cancer metastases of course are derived from the prostate, but once the cancer has spread, there's a tendency for the lesions to spread further. In other words, in metastatic lesions, then are the source of more metastatic lesions. And it certainly makes sense to me. So if that is true, and metastases beget metastases, then of course we not only want to treat the prostate, but we want to treat this early metastatic disease in an effort to stop the spread. And imaging is key for that. If we begin to look at some of the initial data, and this is from UCLA, and this is not a randomized study, we're looking at best PSA response to various focal therapies after detection with PSMA PET. And if you look down carefully, you'll see the surgery and radiation, even a couple of patients with cryoablation that are being treated here, but that waterfall plot is really quite impressive. So the treatment of PSMA detected lesions is something that can unequivocally lead to response when administered to patients.

Now we have a little bit of randomized data using choline PET. This is the STOMP trial. And here you see published out of the Journal Clinical Oncology, was the clear evidence for metastasis directed radiation therapy to be ADT sparing, and have an improvement in PSA progression. And this randomized data is important because it really was the first time that we can demonstrate that metastasis directed therapy could have an effect in a randomized trial. Now we're going to move on to the ORIOLE trial, again, an important trial, relatively small, but quite important. These are recurrent hormone-sensitive prostate cancer patients by conventional imaging, CAT scan, MRI, or bone scan. They had 1 to 3 metastatic lesions. A PSA doubling time of less than 15 months or an ECOG performance status of 2 or better. They were randomized 2 to 1 to receive SABR, which is SBRT directed radiation to the metastases or observation for six months.

Now there are only 18 patients in the control arm, 36 patients in the treatment arm. But again, this is a prospective randomized trial. Patients were followed up every three months and then have CAT scan and bone scan. There was also a PSMA scan obtained, but it was blinded. I'll come back to that here in just a minute. So the primary outcome was progression at six months as defined by a PSA increase of greater than two nanograms per ml. And at least 25% above the nadir, or evidence of new metastases by conventional imaging, CAT scan, MRI or bone scan, symptomatic progression, or initiation of ADT for any reason. So this is the PFS endpoint. And what was found in these patients, first of all, you can see, these are fairly typical. About 68 years old, the majority of them were T2 and T3 at the time that they were initially diagnosed, Gleason score 8 or 7.

The initial management in this series was predominantly surgical, 83% of the patients were surgically treated as their primary treatment. Times of recurrence, right about 2 years, 22 months, and baseline PSA was 6 to 7. So that's the characteristics of these patients. And what you see as metastasis directed therapy was stereotactic body or radiotherapy, significantly improved PFS, the primary endpoint and the hazard ratio was quite strong, the 0.3. Confidence intervals that did not overlap 1. P-value 0.0023. So I think that's pretty impressive evidence that treatment of the metastases can make a difference. And remember, this is conventional imaging. What about PSMA PET? Well, there were patients who had a PSMA PET and it was done in a blinded manner at baseline and day 180. So the 36 patients who turned out to have conventional imaging eligibility treatment planning and followed through with the trial, it turned out that when they began to look at when there was treatment of these metastases, there was total consolidation of all the PSMA radiotracer-avid lesions only in 19. And in 16, there was only subtotal.

So complete treatment of all the lesions by happenstance, because remember, this is a blinded PSMA scan and subtotal in 16. And what happened? If you had no untreated lesions you're on the top part of this curve, on the Kaplan-Meier curve. If you had any untreated lesions, these were PSMA avid lesions, you're on the bottom part of the curve. You can see the hazard ratio was 0.26. P-value less than 0.0055. No doubt about it. When you consolidate all the PSMA avid lesions, you end up with a better PFS. They also looked at metastasis-free survival, a slightly different endpoint, came up with a hazard ratio of 0.19. And again, you can see the difference between having no untreated lesions and any untreated lesions. In conclusion SABR, stereotactic body radiotherapy, or SBRT improves PFS in men with oligometastatic prostate cancer when using conventional imaging compared to observation alone, but total consolidation of PSMA radiotracer-avid lesions gives stronger results. And that's the punchline from this ORIOLE trial.

Now we're going to move on to talking about patients initially diagnosed with localized disease. How good is PSMA PET? The OSPREY trial helps us to examine that. I'm fortunate to be able to have slides that are probably given to me with permission to cover the ASCO GU presentation by Frederic Pouliot. And he gave this initial presentation on OSPREY covering the so-called cohort A, and that's the one I'm going to be covering today. So the OSPREY study design looks at diagnostic performance of 18F DCFPyL PET imaging, which is PSMA PET, in high-risk prostate cancer, and that was cohort A. And use a series of blinded central reads compared to the histology as the truth standard. So that's very important. This trial depended on histology and these were before surgery in order to get to the truth.

They had three central readers to be able to look at the PSMA PET, but they were all blinded to one another. So this is three central and independent readers looking at the PET. And that's going to be reported when we come to the results and one conventional imaging reader. So there were a total of 385 patients in cohort A, there were 268 patients who got the DCFPyL, 252 of these patients went on to have a valuable pathology after a radical prostatectomy and pelvic lymph node dissection. Primary endpoint was sensitivity specificity within the pelvic lymph nodes and a variety of secondary endpoints as well.

Baseline characteristics, patients 64, median PSA, 9.3. There was a mixture of patients with T1, T2, and T3 disease. 96.8% were diagnosed as N0 or NX. M1, it was only one patient with M1 disease. M0 was 98.8%. The Gleason scores were actually a mixture, some 6 and 7s about 19%, 8s comprising, 45%, 9s and 10s about 35%. So what did they find? This is a complex results slide, but first of all, if you look, they're going to be three different central readers. In addition, they're going to be two categories of lymph nodes as shown on the left. One category of lymph node was any pathologic lymph node. And the second category was a lymph node above 5 millimeters. So the 5 millimeter is the issue that was considered to be detectable. If it was below the 5 millimeter cutoff, it was considered to be PET undetectable.

If you look initially at the sensitivity, and you can see there's a difference between the all lymph node group and the lymph nodes above 5 millimeter group. And these three different readers, two of whom are highly concord, and one of whom is a little bit less. So the sensitivities for the lymph nodes above 5 millimeters goes 62.9%, 48.6% and 60%. The bottom line is, you're not going to detect all the lymph nodes. And I think that that's going to be inevitable simply because some of these are going to be quite small and there may even be histopathology differences as well. So specificity was up in the 96 to 98.9% range across the board, positive predictive values moving from 78 to 90% for all lymph nodes, positive predictive values for the lymph nodes above 5 millimeters, 75 to 89.5, depending on the reader and the negative predictive value, we're running about 80 to 83% in terms of those individuals for all lymph nodes and lymph nodes above 5 millimeters running above 90%.

So overall, these were the primary results. You can see sensitivity, specificity, positive predictive value, and negative predictive value data all lined up. And you can see that you're going to be adding value by doing these scans. Now, the patients and their conclusions, they really noted that 96% of the patients had nothing at the time of conventional imaging, but 27% of the patients had N1 or M1 detected on the PSMA PET. And by the way, it wasn't all just about pelvic lymph nodes, about 12% of the patients had frank metastatic disease, the majority of which was in bone. There has been a really big movement forward in terms of December 1st of this year, with the FDA approval of gallium 68 PSMA-11 at UCLA and UCSF. And the wording was very interesting from the FDA. PSMA-11 is indicated for patients with suspected prostate cancer metastases when cancer cells spread from the place where they first formed, to another part of the body who are potentially curable by surgery or radiation.

They did not specify a PSA. They did not specify a particular Gleason score. They just said suspected prostate cancer metastases, so a lot of latitude, and I think this may pre-stage the language we're going to see in the future. The PSMA-11 is also indicated for patients with suspected prostate cancer recurrence based on an elevated serum PSA. Now they didn't specify the type of treatment, they didn't specify the PSA level. So again, a large latitude in the language that the FDA used in this particular approval at UCLA and UCSF. And with that, I'm through with my little presentation and thank you very much for the opportunity to give these slides to you today.

Discussion

Neal Shore: We're back for a discussion to review an outstanding presentation by Oliver Sartor, Professor of Medical Oncology at Tulane, who did a wonderful review of where we are today and the new advances and approvals for PSMA-PET scanning, recent studies that clearly will shape additional trials, and most importantly, what are we going to be expecting in 2021, thereby we can become better diagnosticians.

If we're better diagnosticians, then we can optimize patient care. I'm joined with Oliver today with Alicia Morgans, medical oncologist at Northwestern University, Phil Koo, a nuclear radiology expert at Banner MD Anderson. So, thank you all for being here. I know we have so many questions to ask Oliver. Let me start with you, Phil Koo. You've been spending an entire career understanding the importance of the advancements in next generation imaging and where we're going to evolve in 2021.

I think it goes without saying that it's one of the most important things at the tail end of 2020, and now 2021, the education and the accessibility for these technologies and getting our nuclear radiology medicine colleagues greater involvement is essential.

Phillip Koo: Yeah. Thanks, Neal. And I think over the years that we've known each other, I think we've been talking about this next generation imaging for a while now. I think there's a tendency to over-hype it a little, because we're so excited about something that is groundbreaking, disruptive, and clearly so much better than anything we've ever had in the past. December 1, 2020, was a landmark day in the United States, so I think it's very, very exciting.

What I think we need to think about though is, what are the limitations? And I think Dr. Sartor really highlights the fact that it's not perfect. And Dr. Pienta as well talked about the inability to detect micro metastatic disease. So I think this is where the fun begins. I think there's a lot of questions that are going to be raised, and there needs to be a little bit of a reality check here, with regards to what the tool can do.

And this is where I'm curious to hear Oliver's thoughts. When we're talking about METS-directed therapy, I think a lot of times, people think of NDT as a potential cure for patients with biochemical recurrence. But clearly, I think what we're beginning to understand is, these patients do recur. These patients probably have micro metastatic disease, yet the trials seem to only do SBRT. So Oliver, in your opinion, how should we be looking at NDT? Should we be more aggressive with NDT, where we combine SBRT with other therapies or is what's happening today more relevant in STOMP and ORIOLE?

Oliver Sartor: No, it's a great question. And I talk to patients about this all the time. First of all, I think the NTD really has value. But the question is whether or not it has optimal value. And there's a very reasonable approach to those with metastatic disease called adding hormones. And you might even be able to get some synergy with that and the radiation. It doesn't have to be hormones forever. Maybe it could be hormones for a brief period of time. When it comes to hormones, are we talking about old hormones, like the ADT of old with leuprolide, et cetera, type drugs? Are we talking about the addition of the newer drugs, such as abiraterone and enzalutamide?

And I'll simply say that I really don't know. But it's not uncommon in my practice, after talking to the pros and the cons, that we use the metastasis-directed therapy, typically with radiation, but then we'll add in a brief course ... when I say brief, we've been using about six months of ADT plus or minus abiraterone and enzalutamide. In those circumstances, we don't really understand what the radiation has done until the testosterone recovers. So it's sort of a variant of interment therapy.

Is that right? Is it wrong? I don't really know. We don't have the trials yet. But that's one of the shortcomings and one of the lack of knowledge issues that we have when we talk to patients.

Neal Shore: Yeah, it's an area obviously that's so ripe for us to do clinical research. We need to continue to encourage everyone in the audience to be part of that. Oliver, can you further comment on the trials such as OSPREY, and both ORIOLE and others, where the notion of clinical utilization, how this new information would ultimately change decision-making? I think it's a general open-ended comment, but I think it's really important for our urology and medical oncologies and radiation oncology colleagues listening to recognize that with advanced nuclear medicine-based imaging, there really can be a marked change in one's reflexive decision-making.

Oliver Sartor: Well, absolutely. We're really talk about the distinction between a non-metastatic and metastatic patient, quite a significant percentage of the time. Well, metastatic disease is typically viewed as being incurable. And now we're having to deal with these metastasis discussions in patients in a different way than what we have done in the past.

In addition, we can take that negative scan and talk about the non-metastatic disease in a whole new category. By the way, I think everyone here knows about the FDA approvals in non-metastatic castrate resistant disease. Well, there have been studies with PSMA-PET showing that about 98% of the patients with castrate non-metastatic disease, at least those with a PSA doubling time of 10 months or less, fall into a category of actually having PSMA-detectable lesions.

So as we begin to move into this new period of imaging, we're going to have to deal with a lot of discussions and a lot of issues that heretofore, we've not really had to face.

Neal Shore: Yeah. Great point. And the nomenclature are guidelines for recognizing the difference between M0, the spectrum between M0 to M1 is changing right before our eyes. But Alicia Morgans, I know you must have some challenging questions for Oliver.

Alicia Morgans: Yes. I think that Oliver and I must both be medical oncologists, because we think about a lot of the same things. One of those things are these approvals that we have and what we've been calling non-metastatic CRPC. And we know that these drugs can prolong survival, which is so important, and obviously one of our main goals, in a way that's relatively non-toxic and maintains people's quality of life.

But one of the things that I think we should really emphasize, because we also have this inherent need, I think, to use things like SBRT to try to identify or to eradicate these areas that we can see, is as you mentioned in the ORIOLE trial, if we're going to do that, we really need to hit every single lesion. There is such a difference if we leave any of these areas on the table, and maybe we can make up for some of that difference by intensifying our systemic therapy, but maybe we can't.

I'm wondering if you can comment on your strategy. Are you using PyL-PSMA to identify and then target everything? Is that something that you've now integrated in addition to these intensified systemic therapies in this population?

Oliver Sartor: That's how we're doing it, Alicia. Our goal is to eradicate every lesion that's feasible. Now, the question comes, when the lesions reach a point where they're no longer really able to be handled individually, and I've gone up to about five, I haven't really gone above five. The other thing is the location of the lesion deserves some comment. We've had some difficulty safely radiating mediastinal nodes. Not all the nodes are the same. There's a lot of emphasis on pelvic nodes, because that's where a lot of these nodes are.

But when you begin to move higher into the abdomen, and when you begin to move into the thorax, the nodes are not always as amenable to safe treatment. So that's another factor. But in answer to your question, we do try to eradicate every lesion when at all possible. And then this discussion about hormones/no hormones is often very individualized. And by the way, I might add that not everybody wants to be treated. I've had some patients, they said, "Well, doc, I feel fine. I think I'll go on vacation and see you when I come back."

And you know what? You can't argue with that. That's their personal choice made after careful consultation, and this bilateral decision-making between the patient and physician is ever more important when we add new information such as these PSMA-PETs.

Alicia Morgans: Absolutely. Especially since we don't know the right answer. We don't have the data to tell them the best option, at least in terms of disease control. Because as you mentioned, best option for an individual is going to be highly variable based on what's most important to them. So, thank you.

Oliver Sartor: Well, we're working hard to try to get it right, but we need to do more trials in order to have the information that's optimal for counseling patients.


Neal Shore: Yeah. I appreciate that, and I appreciate your referencing that, where is the tumor burden, the volume of the tumor burden, patient preference? Is it going to be more SBRT? Is it node plucking done in a laparoscopic robotic manner? Will there be adjuvant treatments? These are all interesting.

I'd love for you to comment and then I want to ask Phil Koo to ask you additional questions. But just, Oliver, to comment on this era now that we're into where we use this expression, "personalized therapy, precision therapy, tailored therapy." And I think it's great, because we're not just doing a reflexive decision. We're seeing this now in the space of genomic profiling, but now are we getting imaging possibility, imaging clearly potential now to be more precise in what we decide to do. What would be your message to our colleagues listening regarding the complexity of tailoring therapy in a more personalized manner?

Oliver Sartor: Well, I think the good news is, is that we can become more personalized. Now we have a greater degree of certainty as to where these lesions actually are. How many times has the patient looked at us and said, "But where is my cancer?" We know that the PSA is up. We know that conventional imaging is negative or at least equivocal. "Where is my cancer?" Is a question that we're now better positioned to be able to answer.

But Phil said something important earlier. He talked about the enthusiasm that can, at times, be a bit on the overboard side. We do not have the ability to image every lesion. Even though the consolidation of all the PSMA positive lesions in the ORIOLE trial was an important parameter, we still know that there are going to be sub-detection lesions that are going to manifest themselves in the majority of patients.

And helping patients to understand the uncertainty that we face, as well as the certainty of finding these lesions, walking that balance is really important. So personalized decision-making is now better, but there's still limitations, and we need to provide patients an understanding of the inherent limitations of imaging. We're never going to detect every piece of cancer in the body.

Neal Shore: Yeah. Excellent point. Phil, additional comments?

Phillip Koo: That's a great point, and speaking of limitations, we're learning more about false positives with PSMA-PET, with gallium 68 PSMA, people have reported the solitary rib lesion that is actually normal and not a metastatic lesion. We see ganglions that have uptake that aren't metastatic disease. So I think it's something that I think, as Dr. Iagaru mentioned, it's something that we all can learn, but it does require some skill with regards to interpretation and engagement, and that multidisciplinary approach.

One question I have for you, Oliver, is, how do you approach biopsy or tissue sampling of lesions that you see on a PSMA-PET CT? Is that needed? Because I imagine many times, these are not easily accessible percutaneously.

Oliver Sartor: It's really, really tough, and it varies a little bit according to their assessability. I do like to obtain tissue, if feasible, because it gives us the opportunity to genomically analyze those cancers. Recently, I had a case where there was a left supraclavicular node that was detected. It was a bit of a surprise. We didn't know it was there on physical exam or prior conventional imaging. But once we went back, we could actually see that node.

We went back, removed it, confirmed the histology, and now had the opportunity to do a genomic analysis on the cancer metastasis that was not otherwise possible. So I'll say that it's a matter of convenience for most of the patients. We do take a little bit at face value. We're aware of the ganglions, we're aware the solitary rib issues. We also try to get some type of confirmation. 

We look hard at our MRIs and our CAT scans, maybe too hard at times, to see if there's confirmation on additional imaging. But the bottom line is for tissue confirmation, it's sort of a matter of convenience. And then the artistic aspects of medicine is really in determining is it real? Is it not real? Is it going to be something safe to radiate? Is it something we shouldn't? Should we pursue this surgically or not? A lot of those questions are very personalized, and we just have to deal with it, and we often do deal with it, in a multidisciplinary fashion.

Neal Shore: I appreciate that Phil brought up the dreaded rib lesion when everything else was negative. But do you think now, when you see the dreaded, isolated or oligo-rib lesions based on technetium scan, maybe correlated CT scan. If it's positive now on a PSMA-PET, what's your level of certitude now that, that really is cancer? Because ribs are hard to biopsy, of course.

Oliver Sartor: Gosh, that is such a tough question, Neal. We stare at it with our conventional imaging. We try to determine if there's any sclerosis. We try to determine [inaudible 00:15:46] the rib lesion. Some that are more centrally located or easier to interpret than those that are more sort of the cartillaginous portions. If it's right back, in and around in the spinal region, sometimes it might be explained by an arthritic type change. But it really boils down to interpretation and doing your best, trying to take the PSMA-PET, the conventional imaging. Put it together. And by the way, the bone scan is not always so great, because a lot of these patients have reported that they had a fall and hit the ribs somewhere in the last week or two, and that's another false positive. So you called it the dreaded rib lesion. You're right. It's the dreaded rib lesion.

Neal Shore: I have one more opportunity for both Phil and Alicia to ask you a question, but I couldn't let you leave without asking you about the whole notion PSMA-PET now and its correlations with the future of theranostics. I know you've been leading in this space, so any comments for our audience to be aware of?

Oliver Sartor: Well, thank you for asking, because we didn't put it into the agenda. But I think one of the most important uses of PSMA-PET going forward is going to be in the selection of patients for the PSMA lutetiums and PSMA actiniums, that are going to be the therapies of the future. So the ability to bring a targeted radiopharmaceutical into practice is really dependent on the demonstration of a lesion that is PSMA positive. You're using PSMA as your targeting agent.

So this is a huge area for the future. We've done trials like the VISION trial, fully accrued, not yet reported, using PSMA imaging as a selection biomarker, and whether or not it's a predictive biomarker or not, the trial will answer that question. But it's part of the future that I think we're going to be discussing a great deal about over the next year or two.

Neal Shore: Yeah. Thank you, Oliver. I'm incredibly excited, I think we all are, about the advances now in PSMA-PET scanning, how it's going to really make us better diagnosticians. And then also the therapeutic aspect of theranostics. We're coming up on time. Alicia, do you have any other questions for Oliver?

Alicia Morgans: Yeah. Oliver, I'd love to hear your thoughts on operationalization, because you are the medical director at your cancer center, so I know you think bigger than just single clinics, and you have to think about how do we actually implement these new disruptive technologies. As you think about the PSMA agents that may become available in the next 12 months, there may be several different ones that we have access to. What are the pros and cons, and how do you think we can best implement these in our clinics, both in an academic setting, and then if you have any comments on which agents might be best in a community setting, if there is any difference in how you think about that?

Oliver Sartor: Gosh, so it's a really tough question. On the diagnostic side, of course, I think we'll have gallium-68 and the 18F. Some people will say that the 18F is a little bit crisper. I think a lot of this is going to boil down to convenience in terms of which one you choose. It's the one that will be available. The gallium requires a generator. Generally, most of the 18F is from a cyclotron. Where's your supply chain? How do you have things set up? And working with your imaging department? We work with our imaging department. And then, on the therapy side, well, that's a little bit of a different question. The only thing that could possibly be available in practice in the next year, and that's a little bit of a stretch to think that it can happen, but it might, is the PSMA-617, lutetium-177.

So that's the one that's moving forward now. Of course, there's radium-223, and a lot of the supply chains and a lot of the multi-disciplinary teams have already been built around radium-223. So that type of experience, if you have it in your practice, can be very valuable from the therapeutic side. Diagnostically, it's going to be a whole new game. Work together, different specialties working together, working on your supply chains, working on the availability of the isotopes. All those are going to probably vary from center to center. I'd love to hear what Phil says on that.

Phillip Koo: Yeah, I agree. I think this really reinforces the need to create that multidisciplinary team around not just the diagnostic approach to prostate cancer but the therapeutic approach. For those who have not started on this journey, I think there's still time. There's still time to mobilize the appropriate stakeholders and get people on the same page, talking and working together. So it's going to be tricky.

I think you're right. I think in the end, it's going to be a matter of convenience, what's available in your local radiopharmacy. It's the commercial partners, who are important part of this whole journey, that are really going to dictate what you use and how you use it.

I guess my biggest concern that I voiced earlier is how the payers are going to react. I think this is where I think we even need a stronger voice as cancer providers, not just specialty providers, that something like this needs to be provided for our patients and can't be kept away because of X, Y, or Z. Yeah, so that's my take on this.

Oliver Sartor: [inaudible 00:21:21] for multidisciplinary organization and a united front to make sure that patients get access to this. We don't want to be able to have these FDA approvals and not have them accessible for our patients. We're really going to have to get reimbursements lined up, taken care of, so our patients can benefit.

Neal Shore: Well, thank you so much, Oliver, for a wonderful review of the contemporaneous trials and where we are in the state of access and approvals. 2021 is going to be an amazing year. I'm almost thinking though, we have to be careful about the acronym MDT. We may have to come up with another one, because we have MDT for metastasis directed therapy, and MDT for a multidisciplinary team. We got the MDT1 and the MDT2, but it's all good. It's going to advance patient care.

Oliver Sartor: I love it. I never thought about it in those two terms, but you're absolutely right, Neal.

Neal Shore: Well, thank you so much. Wonderful, as always. Educational. Perfect. And thank you, Phil and Alicia.

Alicia Morgans: Thank you.

Phillip Koo: Thank you.

Oliver Sartor: Okay. Thank you.

 

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