Biomarkers and Imaging in Upfront Metastatic Prostate Cancer Diagnosis

David Morris, MD, FACS, of Urology Associates of Nashville, moderates this roundtable discussion on the mHSPC and mCRPC treatment landscape, alongside an expert panel consisting of John Phillips, MD, of Tennessee Oncology; Jeremy McDuffie, MD, of Tennessee Oncology; Katy Beckermann, MD, PhD, of Vanderbilt University Medical Center; and Alan Tan, MD, of Vanderbilt University Medical Center.

In the first part of their conversation, the group tackles key topics in prostate cancer care, including advances in imaging, risk stratification, and multidisciplinary approaches to patient care. The panel shares insights on navigating high-volume vs. low-volume disease distinctions, the role of PSMA PET scans, and tailored treatment strategies in prostate cancer management.

Watch the second part of this series: Patient Characteristics to Consider for Doublet, Triplet Therapy in mHSPC and mCRPC

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Dr. Morris:
Welcome to the GU Oncology Now program roundtable focused on metastatic hormone-sensitive prostate cancer and metastatic castration-resistant prostate cancer.

I’m David Morris, a urologist in a large private urology group that does a lot of research and patient treatment and management in this area. And I’m here to help moderate between a whole panel of experts that I’d like to introduce themselves and then we’ll get kicked off into our discussion.

Dr. Phillips:
I’m John Phillips. I’m a radiation oncologist specializing in genitourinary malignancies and I practice at Tennessee Oncology here in Nashville.

Dr. McDuffie:
Hi, I’m Jeremy McDuffie. I’m a medical oncologist with Tennessee Oncology. I have a primary practice in Murfreesboro, Tennessee.

Dr. Beckermann:
I’m Katy Beckermann. I’m an assistant professor at Vanderbilt University and I’m a GU medical oncologist.

Dr. Tan:
I’m Alan Tan, I’m an associate professor at Vanderbilt University Medical Center and a general medical oncologist as well.

Dr. Morris:
Thank you guys for joining me. I think first we begin kind of with setting the stage in terms of landscape for hormone-sensitive and castration-resistant prostate cancer. A little bit of definitions, what we’re using in the current marketplace to help put people into certain categories, and obviously a little bit of different kind of experience, medical oncology and radiation oncology.

We spend a lot of our time dealing with localized therapy, but now actually our roles are becoming more involved in later stage disease. So maybe first just for the medical oncologists, any particular markers that you’re utilizing today, especially for upfront metastatic diagnosis? Anything that you’re looking for to help guide patient decision-making, whether it’s molecular, whether it’s imaging, what are you using to help kind of categorize people in different risk categories?

Dr. Tan:
Right, so right now of course PSA is cheap and very reliable, so that’s probably the best biomarker we have. A really high PSA is almost a diagnosis for prostate cancer, but we still usually like to have a tissue diagnosis of this regardless of how high the PSA is because we’re now sending tissue and liquid testing for genomics. But genomics really doesn’t really have a role in upfront treatment. It may be prognostic such as if you have an SPOP mutation that might have a longer progression-free survival versus if you have a TP53E mutation or RB1 loss, that might be somebody that becomes castrate resistant sooner.

So I would say imaging is probably one of the better biomarkers that we use. High-volume versus low-volume, that’s kind of how we think of things as far as do we do ADT plus ARSi or do we use a triplet ADT ARSi plus docetaxel. And that’s really the frontline landscape in a nutshell. There’s different options of course as far as ARSi’s and also the ADT backbones as well.

Dr. Morris:
You mentioned imaging, so big landscape changes over the last few years in terms of imaging and what we’re using, what you’re seeing on referrals from urologists and primary care, how are you making volume distinctions for risk stratification? Are you using conventional imaging? Are you using PSMA? What’s your current guidance?

Dr. Beckermann:
Yeah, I think for us what we’ve seen a lot of is a transition to more novel and sensitive imaging. Certainly still conventional imaging has its place, but I think PSMA PETs have certainly increased my referral pattern from our urologist and radiation oncologist. They’re changing staging, not sure that we really know how to deal with that and hopefully prospective trials to come out to better understand that. But I think a lot of my patients are coming to me now with PSMA PETs.

Dr. Morris:
All right. And Jeremy, you see the same sort of transition to PET imaging as kind of the standard now?

Dr. McDuffie:
Well, we definitely see more PSMA PETs being ordered in the community. I think that one of the big differences, we’re pretty collaborative in the area that I practice in, so I see a lot of these patients early on and I’m actually making that decision.

I kind of use the PSA to kind of guide the decision making that I’m getting for imaging. So if someone comes in the PSA let’s say is above 10, I’m probably not going to start with a PSMA PET scan. I’ll probably look at more conventional modalities because I think I can make decisions that way. If I am working with someone with a thought to be lower stage disease or lower PSA, then certainly look at PSMA PET scan to either further upstage them or kind of downstage them to make therapeutic decisions.

Dr. Morris:
So, obviously we’ve inherited kind of this volume distinction problem from clinical trials from 10 years ago in terms of high-volume/low-volume definitions. Are you basing the decisions primarily off of conventional imaging? If you’re really looking at trying to categorize somebody’s high-volume/low-volume, which what’s the takeaway? Should we be using conventional imaging in that setting? If somebody has seven bone lesions on a PET scan, do we say they’re high-volume, or should we get a bone scan to really restratify? What are you guys doing in practice?

Dr. Tan:
Yeah, that’s a tough one because of course we all want to use the newest technology to see what the true burden of the disease is, but by definition, you kind of have use this charted in the stampede definition of a greater than equal to four bony metastases or visceral metastases has to include axial skeletal disease, but also one at least one non-axial.

Dr. Morris:
Okay. You guys, same in terms of volume distinctions largely by conventional if you can?

Dr. Beckermann:
Yeah, I find at least for me, where I am sitting and talking with a patient with a kind of de novo metastatic, I agree. It’s either they’re coming in with a PSA where there’s no question, I don’t really need a PSMA PET and we can get that on a CT scan.

And then I think certainly those are kind of those initial looks, but we delve in deeper and say, okay, was this a de novo met? Was this a recurrence from 10 years ago to just better understand what the biology of that disease is when we’re making alongside kind of the high-volume/low-volume discussion

Dr. Morris:
Maybe around the idea of low volume de novo disease, that’s probably something that falls a little bit more in your wheelhouse for referrals up front. What’s the current radonc view of how to manage somebody with lower volume metastatic de novo disease?

Dr. Phillips:
Yeah, I think in the era of PSMA PET, it’s extremely challenging. I saw a patient today who by conventional imaging would have no metastases and it has a sclerotic PSMA avid rib lesion. And the question is if rib lesions are very difficult to biopsy and have certainty and a negative results, and so you’re stuck in this sort of treatment conundrum where you say, “Do I treat this guy’s unfavorable intermediate risk disease,” which is what he is when you don’t think about that PSMA PET, “or is this a guy with low volume early metastatic disease?”

I think as radiation oncologists, we are always weighing the toxicity of treating those lesions. So a rib lesion we can treat with stereotactic radiation and ablate with very little toxicity. So in that setting, a lot of guys after you have an informed decision-making conversation are going to say, “Just go ahead and ablate that rib lesion.” Whether it’s cancer, whether it’s not, I believe the PSMA PET.

When it becomes to a lesion that’s somewhere more difficult, that becomes a more challenging conversation. We’ve seen a lot of guys with mediastinal lymph nodes that we would never think were prostate cancer and then we biopsy them and they’re PSA positive.

And so I think that there’s challenges on both ends. Is it truly metastatic disease or is it low-volume versus high-volume? And we’re kind of constantly trying to parse through data that relies on conventional imaging when we have this much better tool for detecting early metastatic disease. And so I tend to err on the side of being very aggressive with these guys because they can have a prolonged biochemical control. But I think that if you surveyed all of radiation oncology, you would find kind of like a 50/50 split between people who don’t treat aggressively upfront and people who ablate five lesions at diagnosis.

Dr. Morris:
It sounds like our guidelines followed the same sort of gist, it’s a choice that you can offer primary therapy, you can offer metastatic direct that’s not in a guideline that it should be done. So it gives us a lot of leeway for that discussion about toxicity profile.

Dr. Phillips:
And I think a lot of times we’re deciding how to sequence and we’re deciding not just based on number, but how big is the metastasis? Number doesn’t tell the whole story. You can have a one centimeter iliac met and you can have a five centimeter iliac met. So we are taking all of those things into account that none of our trials so far really address. And so I think it’s not one-size-fits-all just by a strict number criteria. There’s a lot of nuance in how we think about those things.