PSMA/PET Scans and ADT in Patients With CRPC

In a roundtable moderated by Tanya Dorff, MD, of City of Hope, panelists Michael Morris, MD, of Memorial Sloan Kettering Cancer Center; Benjamin Garmezy, MD, of Sarah Cannon Research Institute; and Yu-Wei Chen, MD, MS, of the University of California, San Diego, discuss new treatments and therapy considerations in the field of castration-resistant prostate cancer.

In the first segment of this roundtable series, the panelists discuss the use of PSMA PET scans and androgen deprivation therapy in the treatment of CRPC.

Watch the second part of this series: Decision-Making When Considering ADT and Doublet or Triplet Therapy for CRPC

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Dr. Dorff:
Welcome. Thank you all so much for joining me for this roundtable on hormone-sensitive and castration-resistant prostate cancer. I’m Tanya Dorff from City of Hope, a medical oncologist, and I’d love for you all to introduce yourselves.

Dr. Chen:
Yeah, my name is Yu-Wei Chen. I’m a medical oncologist at a University of California San Diego. Thanks for having me today.

Dr. Garmezy:
And I’m Ben Garmezy. I’m a GU medical oncologist working for Sarah Cannon Research Institute and practicing here in Nashville at SCRI Oncology Partners.

Dr. Morris:
I’m Michael Morris. I’m the section head of prostate cancer at Memorial Sloan-Kettering Cancer Center, a medical oncologist as well.

Dr. Dorff:
So happy to have this discussion with all of you. To start out, so much is changing in the landscape of metastatic hormone-sensitive prostate cancer, and I’m interested to hear how you’re using PSMA PET scans in categorization of patients in this stage of disease.

Dr. Chen:
Yeah, I think I’ll take on those questions first. Yeah, so I think nowadays it is my standard imaging work for newly diagnosed advanced prostate cancer, and I would like to know how extensive of their disease volume is and thinking about adding potentially chemotherapy as a triplet treatment form. But knowing that so far the chemotherapy data is rely on conventional imaging. But I think realistically just probably unrealistic to get two set of scans, both PSMA and also conventional imaging on our patients nowadays. So I would do most of times the PSMA PET scan.

Dr. Garmezy:
Yeah, and I’ll give you the perspective from the community because what my practice as well as the practice of a lot of my colleagues, we don’t get a lot of CT scans anymore in this phase of the disease unless something doesn’t make sense. So patients are getting PET/CTs up front. We’re doing our best to interpret that for who needs triplet versus doublet because we have to understand that that’s not the way it works. But if we have a PET CT that shows floridly metastatic disease, we’re not going back and getting a CT scan. We’re just going to use that. We’re also using a lot in the intermediate risk localized setting. We’re using a lot to make sure that there’s not oligometastatic disease that we should potentially be doing definitive therapy for as well as SBRT to oligometastatic lesions on PSMA PET. So oligometastatic in quotes, I guess I’ll say.

Dr. Dorff:
Yeah, I was going to ask, do you think it’s appropriate to use the PSMA PET findings in a high risk localized or maybe an unfavorable intermediate to re-categorize them to metastatic?

Dr. Morris:
I feel least comfortable in the really advanced setting using PSMA PET to distinguish between volume of disease and intensity of therapy. I feel most comfortable though using it in the oligometastatic setting to determine what gets irradiated because at least we have randomized studies showing that the use of molecular imaging to be more comprehensive about irradiating the known oligometastatic sites yields better cancer outcomes, that’s at least data. Whereas the use to assess volume in order to decide whether to use triple therapy or not, that really is a no-man’s land for and a data-free zone.

So I actually feel most uncomfortable about the context of using it to determine who gets chemotherapy or not. I think it’s a lot more useful in the lesser disease burden category where PSMA PET actually is furnishing information for which there’s data that is actionable to make a treatment decision on it. In fact, I have sometimes backed away from using PSMA PET in the volume of disease decision because presumably there are those patients who are in, for example, PEACE-1 and were categorized in the low-volume patients not having benefit with triple therapy who would have had a high-volume disease on a PSMA PET. So I almost feel unsure about whether I should be adding those lesions that are otherwise only PET evident to turn a low-volume patient into a high-volume patient.

Dr. Garmezy:
I think that’s a good point, and what I would say is I think we’re doing the best with what we can with the tools. Five metastatic lesions on a PSMA PET, you’re not necessarily going to add in that triplet therapy. 30 metastatic lesions on a PSMA PET, whether or not they have four, on conventional imaging I think this is not a perfect science, and that’s where in community oncology it’s turning into more of an art than a science, which may or may not be fair. And I agree it’s a data-free zone, but it’s just hard when a patient sees that PET scan report to go back and get a CT scan, they’re in clinic with you and then say, well, actually you don’t have that many metastatic spots. So I think that’s just the nature of just the difficulty of actual clinical practice versus data interpretation.

Dr. Dorff:
But what about the flip? What if someone comes to you with a CT bone scan and you think they’re oligometastatic and you want to radiate? Do you get a PET scan to really confirm that or refute it?

Dr. Morris:
I do, yeah. Not so much to confirm or refute, but to guide the decision around SBRT. It would be rare to… I think it’s certainly feasible to go from four lesions to 30 lesions, but you could go from four evident lesions to six PSMA evident lesions. But going back to the high volume situation, there is one circumstance where I would say PSMA PET does make a difference for me, and that’s the detection of early, but otherwise anatomically small liver lesions where the PSMA PET may identify those and that will sway me because I don’t think that those patients are actually undertreated if you give them triple therapy on the basis of what otherwise would be obscured or just too small to see anatomically on a CT. So there is that one… And both of these are actually relatively unusual things, but there are certain circumstances where I think a PSMA PET is appropriate.

Dr. Dorff:
I think Oriole really showed that, right? That if you targeted the conventional imaging disease but missed something that you had seen on the PET, they didn’t do as well, so it makes sense.

Dr. Morris:
Absolutely.

Dr. Dorff:
Now, what about when you’re giving SBRT for oligomet? Do you add antigen deprivation therapy? And how much and how long?

Dr. Chen:
I think it depends on how hard the goal with SBRT is to oligomet. So for example, from a very senior patients that are pretty frail, they probably cannot tolerate the hormone treatments in that regard. I probably would just consider SBRT and follow their PSA and see how is the PSA train is doing. But of course, for more feed patients, I would consider aiding ADT in addition to the SBRT as well. So it really depends on patient fitness.

Dr. Dorff:
And for a low-volume, metastatic or oligomet patient De novo. Any thoughts about lifelong antigen deprivation versus time limited? If you can radiate all the disease you can see?

Dr. Garmezy:
I mean, look, we don’t really know. I think that’s the crucial part here, but we’ve got to do something. And so if I have a patient in clinic that I’m not worried about tolerance issues or anything like that, and we’re not going to dance the intermittent game, I say, let’s do radiate everything we can definitive to the prostate. Let’s target the oligomets with SBRT. Let’s do two years of ADT plus abiraterone. That’s generally what I use in this setting.

But you could make an argument to use whatever else is approved in mHSPC, and then let’s try to get you off with the goal of intensifying therapy to provide treatment-free interval potentially cure in some patients. And I think that has been a very effective strategy, whether or not it’s the correct strategy is to be determined. And there are also trials in this space talking about, well, can we radiate these lesions and then watch or radiate these lesions and add in other type of therapy in there instead of hormones to spare ADT. So we’ll see where the field moves in the next few years.

Dr. Morris:
My thoughts on this is that there is a false equivalence drawn between STOMP and ORIOLE and multiple phase three randomized clinical trials with survival endpoints that involve thousands of patients. And the fact that we discuss denying patients with low volume disease access to life prolonging treatment in favor of some randomized small phase two studies that showed that if you give therapy you delay disease progression is not right. So I do when in the meta scenario, give patients at least a limited course of ADT and an ARSI with the SBRT. First of all, I think that the science stands behind that with the synergistic effects of hormonal therapy and radiation. It’s true for every other context. So why would it be true here? But second, I have such overwhelming evidence that life’s prolonged with ADT and an ARPI regardless of disease burden that I can’t justify on the basis of the existing small amount of data in favor of SBRT making this a choice of one or the other and give both therapies the benefit of the doubt and give both.

That’s not lifelong, but I won’t say that I follow the ORIOLE or STOMP paradigm. For synchronous metastases, I think it’s a little easier. I aim for cure, and I do then give two years and irradiate the limited bone nets that might be there. But there to I’ve done everything I can from a systemic standpoint to get the benefit of the doubt of a survival advantage. And after two years, you’re talking about emerging castration resistance anyway, so the benefits beyond that, I would think you’ve given the patient the benefit of the doubt of giving castration sensitive disease, ADT and an ARPI.

Dr. Dorff:
It sounds like many of us coalesce around the two years for that De novo scenario. But metastatic poses a bit more challenge. And then we have the embark data, of course, also where we’re kind of ignoring PET, but there is the ongoing Era Step that I think is one of the first trials to really actively include the PSMA PET findings and prospectively study that. So hopefully we’ll have some more data.