Expert Insights on the Benefits and Limitations of PSMA PET Imaging for Prostate Cancer

At the 2025 American Society of Clinical Oncology Genitourinary Cancers Symposium, an expert panel convened to discuss the latest research and clinical advancements in prostate cancer diagnosis and treatment. Moderated by Dr. Alan Bryce, City of Hope, Arizona, the roundtable consisted of Dr. Alan Tan, Vanderbilt; Dr. Evan Yu, Fred Hutch/University of Washington; Dr. Priyanka Chablani, UPMC; Dr. Jack Andrews, Mayo Clinic Arizona; and Dr. Chad Tang, MD Anderson Cancer Center.

In part two, the panel explores the role of biomarkers and PSMA PET imaging in prostate cancer management, highlighting the challenges of biomarker adoption in urology and the need for clinically actionable tests that go beyond prognostication. Experts also examine the increasing use of PSMA PET for staging and treatment decisions, addressing its sensitivity, impact on therapeutic choices, and potential to reshape patient classification in metastatic disease.

View the next segment on Oligometastatic Prostate Cancer: Treatment Strategies and the Role of Local Therapy.

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Dr. Bryce: I’ll ask Dr. Andrews, and we’ll shift gears here a little bit. As a urologist, again, where do biomarkers fit in? But what other biomarkers do you think about in the urology world? In the metastatic world we’re starting to talk more about the Cypher or other tests. You guys have a lot more experience with that. What other biomarkers should we be thinking about?

Dr. Andrews: Well, there’s a lot of biomarkers out there. And the problem is, none of them really moved the needle that much yet. And I think we sometimes try and make localized disease more complicated than it needs to be. I think localized disease can be more binary than sometimes what we really are trying to make it. There is a role for biomarkers, but biomarkers need to truly change practice potentially, not just prognosticate on the patient’s prognosis. Probably the biggest role for urology in the localized space or pre-localized space is in the elevated PSA patient, whether or not it’s a biopsy. So somebody with an equivocal MRI, borderline PSA, there are a few biomarkers that will help us decide what should we biopsy? But other than that, a lot of people have different views, and there’s not a slam dunk biomarker for us in urology that says this is going to help the patient and change practice.

Dr. Bryce: Yeah, fair enough. And what about, there’s a hot question of PSMA PET imaging. Where should this fit in localized disease?

Dr. Andrews: Well, I love PSMA PET, so that’s where my research is. That’s what gets me excited. PSMA PET is by far better than any staging imaging that we’ve had for localized prostate cancer before. It does a really good job at detecting widespread metastatic disease. In localized prostate cancer or untreated prostate cancer, about 95% plus of patients will produce PSMA, if not closer to 98%. So it’s very good at detecting disease. It’s also good at seeing the disease within the prostate. However, its sensitivity is still a little bit of an issue here. The sensitivity for nodal staging, which is really what we’re looking for when we’re staging patients prior to radical prostatectomy, is between 30 and 40% depending on whether or not you look at unfavorable intermediate risk or high-risk disease.

And so, PSMA PET is not good enough really for surgeons to omit a pelvic lymph node dissection in the setting of negative nodes. You could make an argument in some cases in patients that are unlikely to have metastatic disease that the PSMA PET doesn’t move the needle. That’s going to change. I think PSMA PET is a huge step forward. But there is still room for improvement, particularly in terms of sensitivity.

Dr. Bryce: Yeah, yeah. All right. Dr. Chablani, we’re talking about the PSMA PET. What about in the metastatic setting, because we’ve got all this data, all these clinical trials talking about high volume, low volume, how we should approach things differently. Now we’ve got a test that’s going to show us more lesions. We could have a Will Rogers phenomenon, very simply. How do you incorporate PSMA PET into the existing data in your decision-making?

Dr. Chablani: Yeah. So, great question. I’m seeing so many new de novo metastatic hormone-sensitive prostate cancer patients just coming with a PSMA PET and no bone scan, no CT imaging. And they’ve been going through the wringer, seeing their elevated PSA, seeing their urologist, it’s been like four months. And then for them to come to me and be like, “Oh, I need conventional imaging now.” A lot of them are not going to buy that—they’re anxious about their disease. So I do find myself making treatment decisions based on the PSMA PET that they’re coming in with a lot of times. I would say if there’s florid mets everywhere, or clearly visceral mets—liver, lung—I’m calling that high-volume disease.

If they have a ton of bone mets, I’m calling them high-volume disease. I’m talking to them about triplets. If they, you know, ADT, darolutamide, docetaxel, ADT, abupred or docetaxel if I feel like they’re fit enough, they’re young. If they meet the other criteria I’m thinking about for triplets. But then there are situations where there are four or five bone mets. And I am thinking, “Is this low volume, or is this high volume? Would it have just been one or two mets on conventional imaging? Do I talk to the patient about triplet or just doublet?” So that’s where I’m finding myself in a gray area, and I’m using other biomarkers such as PSA, and age and fitness. As I said, if they’re in their 50s presenting with metastatic disease, and just like, why do they have such an aggressive biology?

And they’re young, maybe I should talk to them about a triplet even if they just have three or four bone mets. So yeah, definitely fits into how I make my treatment decisions. And I’m really seeing PSMA PET in all stages. Like initial staging after patients come from the urologist for high-risk localized disease, or unfavorable intermediate-risk disease. And then I’m also seeing patients coming in for clinical trial evaluations, where their community oncologist got a PSMA PET in the castrate-resistant setting. So, we really need to get better at how do we interpret these findings and how do we utilize them in clinical practice?

Dr. Bryce: Yeah, yeah. And it’s a hot question. We debate this a lot. We debated this at the US Prostate Cancer Consensus Conference last year, which was an expert consensus conference about how to approach it. I think the variables with imaging nowadays, a few things to keep in mind is PSMA PET is more accurate, more specific, and sensitive than technetium. So right off the bat, the alternative test is worse. And this is an issue. We’ve all struggled with this for decades, of how do you interpret a technetium scan? But I think key things that I would ask, that I would really encourage the practicing clinician to keep in mind—don’t over-interpret a PSMA PET. We’ve seen the data from the UCLA and UCSF groups, when you have solitary rib metastases. They did a series where they biopsied these. And almost all of them, greater than 90% of them, were negative for cancer on biopsy.

And it’s really important, if you’re going to call a patient metastatic based upon a single PSMA PET finding, then you run the risk of taking away the chance for a cure. So really important to keep in mind the difference between metastatic disease and non-metastatic is the difference between cure and not cure. And we shouldn’t take that chance for cure away from a patient. So I’d be very, very careful about over-interpreting small findings on a PSMA PET. Having said that, a patient with florid disease, 30 metastases, that’s easy. But then I would also say in the patient with 30 metastatic lesions, what’s the difference between having 30 metastatic lesions or 34? Absolutely nothing. So finding four more lesions doesn’t change anything. So I agree with you. I get PSMA PET more often than conventional imaging nowadays.

But if for insurance reasons or any other reason I have to get conventional imaging, it’s okay. We can still proceed. We can still make our decisions. I think the other thing I would emphasize is, it takes a lot less time for the patient to get one scan instead of two. In terms of that investment, in terms of the cost, it’s not actually that much more at the end of the day when we take all the time into account. So I think we know, we see the real-world data, the field has shifted. It will continue to shift in terms of PSMA PET. And I would say that it is incumbent upon us, the researchers, to provide the data that lets people use this test in the best possible way.