Transcription:
PSMA-Targeted PET Imaging for Prostate Cancer

Melanie Cole (Host): Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole and today we're so excited to discuss the PET-PSMA imaging for prostate cancer and the recent FDA approval of Pylarify for prostate cancer detection as Northwestern Memorial Hospital is the first site in the Chicagoland market to perform prostate imaging using this agent.

Joining me in this panel discussion is Dr. Edward Schaeffer. He's the Chair of the Department of Urology and the Edmund Andrews Professor of Urology at Northwestern Medicine, Dr. Ashley Ross. He's an Associate Professor of Urology at Northwestern Medicine and Dr. Hatice J Savas. She's an Assistant Professor of Radiology at Northwestern Medicine.

Doctors, I'm so glad to have you here. This is really exciting for this Chicagoland market and this area in the Midwest. Dr. Schaeffer, I'd like to start with you, if you would tell us a little bit about the history for tracking metastases in prostate cancer. What's different now what had been done before?

Edward Schaeffer, MD (Guest): Thank you. For individuals who have a new diagnosis of prostate cancer, or for those individuals, who've had their prostate cancer treated and by the blood test, it has appeared to come back; we will need to do something called staging and the staging traditionally has been designed to look for spread of prostate cancer to the lymph nodes, to other soft tissue organs and to the bone. And the way that we have historically evaluated a patient for advanced or spread metastatic disease has been to use a combination of radiographic tests, CT scans, MRIs, and bone scans to comprehensively evaluate a patient for the advancement of their disease.

And although these tests have been effective and used for decades, they do have limitations in terms of their accuracy. And also they have limitations as would often require multiple tests to get the single answer that one is looking for.

Host: This is really so exciting. Dr. Savas, as the radiologist, tell us a little bit about PSMA-PET imaging agent Pylarify. And tell us a little bit about how this imaging tool really works.

Hatice Savas, MD (Guest): Oh, thank you so much. As Dr. Schaeffer stated, we were looking for other testing, other imaging modalities that can find prostate cancer cells better. So, we are using a PET scan here. It is short for positron emission tomography scan. It's an imaging technique that uses radioactive tracer to clearly image targeted areas in the body.

In this particular imaging method, PSMA-PET scan, the compound is a small, very small fluorinated, radioactive molecule injected intravenously, and specifically binds to the PSMA protein. And this, protein, often found in large amounts on the surface of prostate cancer cells. So, with this method, we are able to see more precisely the lymph nodes, involvement of bone and soft tissue metastases to determine the presence or absence of recurrance and also, very helpful for initial staging as well. So, PET is a scan, usually combined with CT. That's why we call it PET CT scan, which give us like a capturing high quality anatomical imaging.

And with the PET, we are detecting small molecules, in this case, which has prostate cancer cells and PET CT as a combined imaging and allows us to create accurate superimposed single image technique, which no other imaging modalities can replicate it.

Host: Dr. Savas, can you also discuss Northwestern's unique ability to perform this imaging using a hybrid technologies? And how did this come about?

Dr. Savas: At Northwestern, we are so proud to have state of art digital PET CT technology, which has a better diagnostic capability in patients detecting small lesions, with much shorter imaging time, with better image resolution. Patients will spend less time in the scanner, which is a big plus, and also it will help us to scan more patients if we need through each day. And I should emphasize Northwestern's unique ability to perform this PSMA targeted PET imaging by using the new hybrid imaging technology, which is called PetroMar. PetroMar is a cutting edge technology that combines PET images with fully diagnostic three tesla MRI that gives excellent soft tissue anatomic information, definitely less radiation and better comprehensive diagnosis. With this technology, the scanner allows us to get simultaneous MRI imaging and as an institution, we are proud to have this technology here at Northwest more than four or five years. And, we are the only institution in Illinois to have this technology.

Host: So, Dr. Ross moving on to you and thank you so much, Dr. Savas for telling us about this exciting technology. Dr. Ross, what patients are ideal candidates for this test? Tell us about patient selection for a minute.

Ashley Ross, MD, Ph.D (Guest): Yes. As mentioned by, Dr. Schaeffer, the ideal candidates are patients for which you are concerned that there might be metastatic or disease, meaning disease outside of the pelvis or outside of the prostate. And those patients fall into two categories. One type of patient is the type of patient who has not had any treatment in the past. They're presenting to you with newly diagnosed prostate cancer. If their disease has features where the cells have characteristics in which they could potentially leave the prostate; these are people who have higher grade disease, for example. Those people can benefit from this more accurate staging. Here, when compared to conventional imaging technologies, PET-PSMA, can not only provide for the more accurate staging, almost a 30% more accuracy, but additionally, has less radiation exposure sort of hinted to by Dr. Savas's comments than conventional imaging modalities.

The other type of patients where this is extremely helpful is patients after initial local therapy. So, initially say they've had a radical prostatectomy or radiation to their prostate and based on their rising PSA level or other serology based markers; so blood-based markers, you're suspecting that they may still have disease either locally or distally from the pelvis and prostate. In those scenarios, early intervention with second line salvage therapies, for example, radiation after prostatectomy can be very helpful.

And so you want to intervene when the PSA is low, however, local therapies are not helpful if the disease is widespread. Conventional imaging at those low PSA levels, for example, under 0.5, nanograms per mil in the post-treatment setting, usually will not detect any disease and it will be uninformative. But with these newer PET agents like PET-PSMA, you can detect recurrences and localize them in about 40% of men. And that can guide your next treatment selection and allow for improved outcomes.

Host: Such a very exciting time for this field, Dr. Ross continuing for a minute. How do you envision, and I'd like Dr. Schaeffer to answer this question as well, but Dr. Ross, how do you envision this will change your practice as a result of this approval and how does it translate to patient care?

Dr. Ross: So, it already has had a fairly significant role in my practice since Northwestern has started to implement this. PET-PSMA has been used in other countries extensively, in the US in clinical trials, extensively. Trials, for example, one's going on at Northwestern, one's at other institutions.

And it allows for the more accurate up front staging and also for less radiation exposure, as I mentioned. So, in my practice already, if a man presents with unfavorable intermediate risk, prostate cancer or high risk disease; these are AJCC staging, 2C and above disease. I will get that staging as opposed to conventional imaging in the last few weeks, I've been able to do that.

And we will find that there's patients that I was thinking about curative, local therapy on, that now we have demonstrated that they have very likely metastatic disease. And obviously that will change our treatment approach dramatically. In the second setting, I've had patients that are after prostatectomy in my hands who had aggressive disease, who have PSA's that are rising and we're considering salvage therapy just to the pelvis and prostate area. And already I've had patients that with the PET-PSMA scan, it shows that there's distant metastatic lesions. And again, we'll have a large change in our treatment management due to that.

There's one more scenario where essentially we can fine tune the treatment plan based on the PET-PSMA findings. So, I think that PET-PSMA come to replace conventional imaging to a large extent, particularly the technetium 99 MDP bone scan, which is plagued by some poor sensitivity and specificity. But I would appreciate Dr. Schaeffer's thoughts of this as well.

Edward Schaeffer, MD (Guest): Dr. Ross, I totally agree with your comments. There are really these two critical areas. Optimization of initial staging that is determining if the cancer has spread and if so, where, and then secondarily in individuals who have already had a definitive prior treatment and then have had a failure, their treatment didn't fully work.

And I think those are two of the core areas where we can use the scan. The other area that will also be important, particularly for our colleagues in medical oncology will be for those individuals who regrettably their cancer was picked up later and there may be concern for more advanced disease and fully understanding where and the exact burden of metastatic cancer these patients may have, can be helpful in refining the treatment that they're offered and also could be helpful for in those situations, potentially having a biopsy done of a suspicious area to help refine the future therapy. So, lots of opportunities to enable us to be more accurate and in understanding of a patient's disease and by being more accurate and understanding a patient's disease, I think we can be more precise in what we offer the patients. And I think ultimately it'll be a big boost for how we treat and manage almost all men with prostate cancer.

Host: Dr. Shaeffer, can you expand and tell us a little bit about your clinical trial involving Pylarify? What are the next steps for this research now?

Dr. Schaeffer: So, at Northwestern, we'd have a great team. And our team has had been aware of this compound for four to five years. And in fact, Dr. Ross and myself were authors on some of the earliest publications, really establishing a Pylarify or its generic name of a PET-PSMA as the future.

And so when Northwestern Medicine brought this PET MRI technology to Illinois at that same time, the company was sponsoring opportunities for clinical trials to better study Pylarify as a compound. And so I took that opportunity, almost five years ago now to develop and initiate a clinical trial that combined Pylarify with MR PET technology. And at that point, we were really first in field to do that. Particularly first in the US to do that. And so that study, has just completed and we're waiting to analyze the results of that study to understand if when you do combine MRI with Pylarify, can you get a better sense of the local extent of the tumor within the prostate and potentially the lymph nodes?

So, upon completion of that, we are now opening our second wave of clinical trials, which will further refine our understanding of the precise distribution of the cancer within the prostate. So, for men who maybe have less aggressive disease, but we want to fully develop a roadmap for the locations of the tumors within the prostate, by combining Pylarify with our MRI PET technology. So those will be exciting next phases. And the great news is that for the last four years, we've been able to bring what is now an FDA approved technology to our patients in Chicago, through a clinical trial and then once that trial effectively ended, the timing was perfect, the FDA approved the compound for use and we've been able to rapidly transition from using it in phase two trial setting to standard of care setting, which has been spectacular.

Host: I'd love to give you each all a chance for a final thoughts for this exciting episode and Dr. Ross, starting with you, just future directions in the field of Urology with PSMA. And tell us a little bit about what you're looking forward to.

Dr. Ross: Yeah, I think there's two pieces of this technology that excite me in terms of like, what I see as is the future. One is, some things are just better. And we see a step-wise evolution as we go through medical technology. And this is definitely a large step forward. Functional imaging with PET scan is simply more accurate. And as I mentioned, can provide for less radiation dose to the patient. So, simply this is better for staging. It allows us to have better knowledge of the disease. And I'm looking forward to having this technology have widespread implementation, having centers like Northwestern lead in the understanding of how we deal with this new information, which as I mentioned, is superior in terms of accuracy, but it opens up questions about how do we treat, in a situation where we could see disease that we never saw before.

The second way in which I'm excited to see the field, from an imaging standpoint is what Dr. Schaeffer mentioned, with PET scans being more accurate, as Dr. Savas also said with PET MR technology, we can be even using this to understand which patients might harbor more aggressive disease than we thought, even within the prostate, and maybe across spectrum of disease, we can have PET imaging help with the staging of all men. Finally, and we didn't spend much time on this, but in addition to these imaging compounds, there are also therapeutic compounds that are linked to these. And there's a lot to be done in the field of theranostics.

This is linking both the radiologic understanding of where prostate cancer is to treatment of that disease. And that is already being shown to help in some advanced disease settings. And that will be being brought forward earlier into the disease state.

Host: Dr. Savas, I'd like you to just sort of expand on what Dr. Ross just said about where radiologic imaging is for prostate cancer and what you are looking forward to seeing in the future.

Dr. Savas: I totally agree what Dr. Ross said. Definitely we need more accurate and precise method to use for initial diagnosis. And this PET-PSMA technology will help us for that. And also for recurrent disease evaluation and one maybe extra addition to what we have been talking so far is in the future right now, we are not using it, but maybe in the future; we may use this type of technology for treatment response analysis, for some certain type of patients.

And as Dr. Ross said, it's also very great technology coming on right now for targeted treatment of prostate cancer, precisely targeting the PSMA receptors. And I think this imaging modality will guide us to patient selection or better targeted treatment in this situation. We know it's a cost to scan, but after further experience and benefits from the scan, I'm sure it will be widely used and then the cost will come down.

Host: And Dr. Schaeffer, last word to you as a first mover in this technology, what else can you share with urologists about Pylarify?

Dr. Schaeffer: I would like to broaden my comments to say that what is most exciting to me about this technology, is the collaboration that we have at Northwestern Medicine. So, when we view taking care of our patients, we don't view them from departmental perspective. We view them from the patient perspective and the collaboration that we have with nuclear medicine, body imaging, medical oncology, radiation oncology, urologic oncology; that collaboration that comes together to identify new opportunities to rapidly transform those new opportunities into reality, realities for our patients, to me is pretty amazing. And it makes me really proud of our team here. So, bringing Pylarify to the Chicagoland market first is one example of what a great network we have and what a great team we have. And that makes me feel good coming to work every day.

Host: Very well said, Dr. Schaeffer. Thank you so much, all of you for joining us today and telling us about this exciting technology available at Northwestern Medicine. To refer your patient, or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine podcast for physicians. For updates on the latest medical advancements and breakthroughs please follow us on your social channels. I'm Melanie Cole. Thanks so much for tuning in today.