PSMA PET Imaging Hot Topics - Neal Shore & Jason Efstathiou

November 4, 2022

Neal Shore and Jason Efstathiou join Alicia Morgans at APCCC 2022 to discuss the current landscape in PSMA PET imaging. Drs Shore and Efstathiou share their thoughts on the agents they are using and the impacts of these new developments in imaging on staging and prognostication.

Biographies:

Jason Efstathiou, MD, Radiation Oncologist Professor of Radiation Oncology, Harvard Medical School, Vice-Chair, Faculty & Academic Affairs, and Director, Genitourinary Service, Department of Radiation Oncology, Clinical Co-Director, The Claire and John Bertucci Center for Genitourinary Cancers, Boston, MA

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

Alicia Morgans, MD, MPH, Genitourinary Medical Oncologist, Medical Director of Survivorship Program at Dana-Farber Cancer Institute, Boston, Massachusetts


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Introduction to Gallium-68 PSMA-11 for Diagnostic Imaging of Prostate Cancer - Tom Hope

Read the Full Video Transcript

Alicia Morgans: Hi, my name is Alicia Morgans and I'm a GU medical oncologist at Dana-Farber Cancer Institute. I'm so excited to have here with me today, Dr. Neal Shore, who is a CMO urologist at GenesisCare, and also, Dr. Jason Efstathiou, who is a radiation oncologist at Massachusetts General Hospital. We are excited to be here at APCCC 2022. Thank you both for being here.

Jason Efstathiou: Pleasure to be with you, Alicia.

Neal Shore: Thank you.

Alicia Morgans: So, I wanted to talk with both of you about PSMA PET imaging, which is really changing the way we think about staging and understanding our patients, their prognosis, and how we want to move forward with treatment. And we'll start with you, Neal. Can you share with us a little bit about which agents you're using, how you choose among these agents. Does it matter? And when are you really integrating them into that process for the treatment of your patients?

Neal Shore: Yeah, thank you. So, in the US, we've lagged behind other parts of the world in terms of getting approval for PSMA PET. In May of 2021, we saw the approval of the 18 FPYL, the Pylarify scan. We recently in December, had the approval of the gallium PSMA PET, the Illuccix. So now in 2022, I think urologists, radiation oncologists, medical oncologists, anyone who's treating prostate cancer can afford themselves of both of these scans. There're more to come. So it'll suddenly have an embarrassment of riches where we had nothing and now we're going to have several agents to choose from. I think from talking to experts such as Jason and our colleagues in nuclear medicine radiology, I mean, all of these scans are probably going to be equivalent in terms of identifying PSMA expression, which will be important for the theranostics component. But the other component, as you say, is staging and how do we better understand making decisions on localized prostate cancer, particularly those who are high risk as well as patients who have biochemical recurrence.

Alicia Morgans: Absolutely. And as we're thinking about staging patients, Jason, I think we have to think about not only how we stage them, which of course is important for potential prognostication, but as we're thinking about that, does it influence at this point, your understanding of prognosis and does it influence the treatment and the outcomes for your patients?

Jason Efstathiou: I think absolutely. There's been a huge clinical unmet need for better staging, better, higher sensitivity, higher specificity imaging. Conventional imaging has underestimated tumor burden and PET is helping a lot. It functions better, it's accuracy is better, and it's hopefully we think localizing clinically relevant tumor burden, and that's the question. We know that the use of PET-based imaging is impacting clinical decision-making, it's changing our management, lots of data to support that, we're personalizing therapy. The question is, does that improve the outcomes? And now I think there's some emerging data to suggest that maybe it is.

There was an interesting study from Emory called Empire One that introduced randomized patients to having a PET in this case was fluciclovine PET, or not. And then mandating how their salvage radiation therapy was designed based on those results. And that showed improved three-year event-free survival by the use of PET. We also have lots of data emerging using metastasis-directed therapy such as SBRT and some data suggesting from the OReO trial for example, that total consolidation of all PET avid lesions leads to improved not only progression-free survival, but metastasis-free survival. So I think the outcome data is emerging, we need more, but it's emerging.

Alicia Morgans: Absolutely, and it's certainly an exciting time. And as you said, we are changing our management based on this. Neal, I'm wondering from your perspective, when you're seeing a new patient maybe with unfavorable intermediate or high-risk disease, and you're thinking about using a PET scan for this patient, how does it actually change your management as a urologist? Is it really doing anything when you're making those treatment decisions?

Neal Shore: Oh, I think it does, absolutely. I think so. Whether you're a urologic surgeon thinking about a prostatectomy for a patient or a radiation oncologist, I think most of us are getting an MR for better anatomical understanding of the disease, but also now a PSMA PET. So from a surgical standpoint, it could influence the landmarks for doing the node dissection. Somewhat still controversial if indeed it's a negative PSMA PET, I don't think anyone's suggesting don't do a node dissection.

Similarly, depending upon the results of the PSMA PET, and particularly in intermediate to high-risk localized, as you're saying, could it affect the radiation oncologist pelvic field windows? So I think this is really important. And I think it may also have implications regarding even systemic therapy if there's disease that suggests it outside the pelvis. So very, very important. I would agree wholeheartedly with Jason that we need better outcome measures and those are forthcoming. I would go back and also add that the fact that we have other trials looking at RH PSMA PET utilizing PSMA PET with copper alloys, there's really this expansion of this is really dramatic and a lot more trials to come.

Alicia Morgans: Absolutely. I have to say in my own practice, I'm adding abiraterone sometimes when there's node-positive disease or planning radiation, and we only find the nodes not by size, not by MR, or CT, but really by PSMA PET, which I think is really important. And Jason, I'd love to hear your thoughts. Are you doing similar things in your practice and what else do you need to really help you and the team understand how to best utilize these emerging technologies or technologies that have already emerged to best optimize patient care?

Jason Efstathiou: No, great, great question, Alicia. Yes, we are using this in our practice. And one of the big things, well, what are we doing? We're changing our radiation field design. We're boosting disease more, PET avid disease like with metastasis directed therapy. We may be intensifying treatment, bigger fields, intensifying with systemic therapy, as you've just alluded to. Yes, we need some more outcome data. So what do we really need moving forward? We need prospective studies that incorporate imaging correlates. Ideally, randomized trials, though that's tough to do as PET becomes standard of care. Okay. Really tough. But ideally, randomized trials with long-term clinical outcomes. We need to reconcile PET with study design, sample size calculations, study eligibility. We need to reconcile PET with the data that exists on therapeutics and their outcomes in a post-PMA era. We need to evaluate PET as a biomarker to look at. Can it inform how patients are going to respond to something like lutetium, right?

We need to also reconcile PET with existing other biomarkers we may be using … genomic classifiers. We need to look at artificial intelligence and say, using radio make sort of based machine learning. Can we evaluate PET metrics to understand disease features even better? And at the end of the day, as Neal has nicely pointed out, there's a host of PET tracers out and they all have some different pros and cons, and it's exciting that we're, there's this wealth of options that's emerging, but we really need some standardized kind of reporting and interpretation guidelines as well. So a lot that we still need.

Alicia Morgans: And I think that's great because when these technologies come into our practices, I think of course there's going to be a to-do list. It will keep us busy for many years, but at the end of the day, I think it really will help patients and personalize their care, as you mentioned earlier. Well, I thank both of you so much for your time and your expertise today. Thank you.

Neal Shore: Thank you.

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