Tumor Board Reviewing PSMA PET in the Care of Prostate Cancer Patients – H Jacene, A Kibel, P Nguyen & A Morgans

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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 share with everyone, Dana-Farber Cancer Institute Prostate Cancer Tumor Board, where we're really evaluating and investigating the use of PSMA PET in the care of patients with prostate cancer. Let me introduce my colleagues first, Heather Jacene.

Heather Jacene: Evening, everybody. I'm Heather Jacene, the clinical director of nuclear medicine and PET CT at Dana-Farber.

Alicia Morgans: Thank you. Next, Dr. Paul Nguyen.

Paul Nguyen: Hi everyone. I'm Paul Nguyen. I'm the head of the genitourinary radiation oncology group at Dana-Farber and professor of radiation oncology at Harvard Medical School.

Alicia Morgans: Last but not least, Adam Kibel.

Adam Kibel: Hey. I'm Adam Kibel. I'm the chief of urology, both the Dana-Farber Cancer Institute and at the Brigham and Women's Hospital. Excited to be here today.

Alicia Morgans: Wonderful. Let's get started. Our first patient is patient XY. So Mr. XY is a 76 year old man with a history of hypertension and an active lifestyle. He really takes pride in walking around his neighborhood on a daily basis, to run errands. His daughter says that he never stops.

In July of 2021, his PSA increased from a baseline in the 10 to 12 range, to 16.64. It was for years, about 6.5 on annual checks.

October 2021, he had an MRI of the prostate that showed a PI-RADS 5 lesion on the right. It was positive for extracapsular extension and mildly enhancing lesion of the right ischium. He had some questionable pelvic lymph nodes, up to eight millimeters.

November of 2021, he had a prostate biopsy that showed a Gleason 4+5=9, Gray Group 5 prostate adenocarcinoma, with an intraductal component.

In November of 2021, he also had a CT chest/abdomen/pelvis that showed right periprostatic lymph nodes that were concerning for disease, up to one centimeter. No evidence of metastatic disease though elsewhere.

In November, he also had a bone scan that was negative for evidence of metastatic disease in the bone.

He was referred for a second opinion and his imaging was reviewed. A PSMA PET scan was ordered and his case was reviewed in tumor board. So let's take a moment to look at the imaging. Dr. Jacene?

Heather Jacene: Thank you, Alicia. Here we have his PSMA PET CT scan. This image that I'm circling with my arrow, is the maximum intensity projection image.

First, we can see some normal structure. So, you can see normal uptake in lacrimal, parotid, and submandibular glands. There's intense, but normal uptake in the kidneys, the ureter, bladder. You see normal uptake in the liver and in the spleen.

If we move right to his prostate gland, we can actually see that there's very intense PSMA uptake in the right posterior peripheral zone. That extended from the base, down to the apex. But in addition to this disease in the prostate gland, he had several lymph nodes that were also positive.

I'm going to actually start higher up in the abdomen and then scroll down. You start with some retroperitoneal lymph nodes. There's a small node with PSMA uptake. This is about four to five millimeters. There's an additional lymph node right here.

As you come further down, we start to get into iliac, external iliac lymph nodes. There's also internal iliac lymph nodes. I highlighted these all by the blue arrows.

You can see the intense uptake in the nodes. This one had a little bit less activity. You can see that the largest node was about a centimeter, but a majority of them are probably between five and seven millimeters.

There was a perirectal lymph node, which was about four millimeters. There's another perirectal lymph node with intense uptake. And there was another internal iliac lymph node, another node anterior to the bladder, in this fat. This is the ureter, and then you're getting into the prostate gland.

And then really, in addition to these lymph nodes, some unexpected findings was focal intense uptake in the left occipital bone right here, which is intense. There was no correlate on the CT scan.

In addition to that, in the right ischium, there was a small focus that had less intense uptake, but nonetheless, it was asymmetric compared to the other side.

The summary of the findings was disease that was known in the prostate gland. There were scattered lymph nodes throughout the pelvis and in the lower abdomen. And then at least one definite, unsuspected bone metastasis and a possible second node.

Alicia Morgans: Dr. Jacene, can you talk us through what your thoughts are on that lesion in the occipital bone without the CT correlate? Because I thought you described that really well to me, when we had a conversation earlier, in how you differentiate that or think about that in terms of probability of being cancer, given the lack of CT correlate in this particular instance.

Heather Jacene: Sure. The first thing I think is important, is to remember that PSMA is imaging the prostate cancer cells themselves, compared to a bone scan, for example, which is imaging the osteoblastic activity around the tumor cells.

When I don't see a CT correlate with something so focal and intense as this, I often worry about it more because I know that I'm looking at the bone marrow disease, which has not yet caused sclerosis on a CT scan or sclerosis to cause activity on a bone scan. So, I always feel more worried when I don't see a CT correlate, than as to when I can find some degenerative changes or a benign lesion, for the etiology of that lesion.

Alicia Morgans: I think that's just so important to emphasize, because I think when I'm looking at a bone scan, for example, if I see a correlate, then I get more concerned sometimes, that that's related to prostate cancer.

But in this case, it's the absence of the CT correlate that actually raises suspicion, because you're really imaging the cancer cells, even before they've had the opportunity to cause destruction in the bone marrow. It's just very interesting and unique.

Heather Jacene: Yes, exactly. Sometimes you might see this on an MR because that's also really imaging the bone marrow, but that's why really understanding the tracers and what they're looking at, is helpful to think about the etiology of these lesions when we see them.

Alicia Morgans: Great. Thank you. Well, let's go back to the case and think through it as a team. So Adam, as the urologist on the team, what are your thoughts? Is this still a surgical candidate? His conventional or CT bone skin imaging was negative.

Adam Kibel: Yeah. I think that's something we're wrestling with for the past year. I mean, this is exactly the kind of patient that I would've enrolled in one of our neoadjuvant trials, where we give patients a very strong hormonal agent prior to radical prostatectomy and has led to the Proteus Trial, which is fully accrued. We're going to wait to see it reads out in the next few years.

But now we have these patients, where clearly we have a met that looks like it's in the skull. We have retroperitoneal lymph nodes. And then we have lymph nodes in the perirectal area, which are not within the surgical field, though maybe within the radiation field.

When I see somebody like this, that has metastases that are not really in what I would call the surgical field, that would be the area that we do our lymph node dissection or right around the prostate.

At least right now, I'm much more inclined to send them for radiation. I think about radiation, even in those that have lymph nodes that are in these other areas, that presumably we will resect.

Back of my mind, I'm wondering, is there metastatic disease elsewhere, that even the PSMA PET can't identify?

Alicia Morgans: I think that's a great question. Not one, of course, that we can answer, but a great question. Paul, ball's in your court, as the radiation oncologist. What do you think about when you see this kind of a scan and this patient history?

Paul Nguyen: Yeah. It's an interesting scenario, that we really didn't have until just a few months ago, when we started getting PSMA scans. We would have taken this patient, and we would've just scratched our heads.

Looking at the conventional imaging, there are certain things that are a little bit suspicious, but nothing that was definitely positive.

What the PSMA has given us now, is kind of a retrospectiscope that tells us that, hey, all of this stuff that we kind of saw on the conventional imaging, was really real and then showed us all of this extra stuff.

I think as a principal, I feel that we generally shouldn't be depriving patients of potentially curative therapy, based on PSMA only findings, given that we were treating these patients curatively in the past.

I think for this patient in particular though, it's kind of a mixed picture situation, because you could argue that we already had some suspicion, based on the conventional imaging.

It's sort of like the PSMA just confirmed it, even though an official call wasn't made on the conventional imaging. So, this is kind of a hybrid patient, is how I view it.

I think that the PSMA is telling us that the right ischium, that was suspicious on the original MRI, really is real. Some of those lymph nodes really are real.

If I looked at it on that basis, I think this patient would be a candidate for some kind of definitive local therapy with radiation, using the STAMPEDE criteria, which we talk about a lot in our tumor boards and when we see patients.

As we've discussed, certainly in tumor boards before, the STAMPEDE Trial in the Arm H, looked at patients that had olig metastatic disease. Well, actually looked at patients that had all sorts of disease, but found that in the patients that had low volume metastatic disease, based on the original charted definition, that those patients appeared to benefit significantly from localized radiation to the prostate. They had a significant overall survival benefit, with a hazard ratio of 0.68, meaning a 32% relative reduction in death.

This patient, I think would meet the original STAMPEDE definition, based on the charted definition of low volume disease.

So, I would propose to treat this patient to the prostate. Because the lymph nodes are there, I would treat the lymph nodes as well.

Treatment of the lymph nodes wasn't part of the STAMPEDE Trial, but it's hard to not treat the lymph nodes, given that they are there. We know that it's not that toxic to treat them. And we know that for high risk disease, treating the pelvic lymph nodes does appear to improve metastasis-free survival.

Then on top of that, where we have these two bony metastatic lesions, potentially, I would refer to my colleagues and see whether SBRT to those bony lesions would be possible.

Whenever it's in the skull region, that's always more risky. So, I'm not a hundred percent sure that we would actually do that one. But the other bone that's in the ischium, certainly that could be treated with very little risk of toxicity.

Alicia Morgans: Thank you so much for bringing up STAMPEDE. I think as a medical oncologist, I absolutely kind of lean on that trial in so many cases, for consideration of systemic therapy.

In this particular case, whether I'm thinking about Arm H and radiation of the prostate in the setting of low volume metastatic hormone-sensitive disease, or whether I'm thinking about it in terms of ADT and abiraterone, which is really how I'm thinking of this patient, ADT and abiraterone with definitive local radiation for that two-year systemic therapy, kind of intensified therapy in the setting of, in this case, borderline clinically positive notes, but clearly clinically positive on PSMA PET.

I think that radiation of the prostate, for me, is absolutely something that should happen for this patient. And then working with you and team members, I would advocate for radiation of whichever pelvic nodes they feel are suitable, as well as potential SBRT and intensification of ADT plus abiraterone, for that two year duration.

I think it's interesting to try to sort out STAMPEDE in the setting of a PSMA PET, because when they called a clinical positive node on STAMPEDE for the ADT, abiraterone for localized disease or locally advanced disease cohort, they were calling that on conventional imaging. So, I do extrapolate that to PSMA PET positive.

At this point, I'd love to hear from you, Heather, what your thoughts are on medical oncologist, radiation oncologist, urologist, extrapolating from a clinical positive on conventional imaging to PSMA PET. It's very tempting to do, and we do it.

Heather Jacene: Yeah. I'm not sure I have the best answer, but I think that if it's... clinically, you're probably going to have more... The patients who are clinically positive on conventional imaging, are most likely going to be PSMA positive on PSMA PET.

So, you're going to catch perhaps, disease earlier, or you're going to be treating disease earlier, because the PSMA PET is more sensitive than what you're seeing on the conventional imaging.

There's some cases like this one, where the disease is probably there and you're confident about it and that, maybe it would manifest it because it would manifest over time, because you have those hints from the conventional scans already.

But I think that there are other ones where you may not, because the disease may not have... you may not have ever seen it on the conventional scans. Those are the ones that we don't know what to do with.

It's also possible that subclinical disease would've been treated by two years of ADT and abiraterone, if they were in that cohort anyway, but we just never knew it was ever there to start with. So, I think it's still going to be a challenging question.

Adam Kibel: I think one of the interesting is, in the future, patients will get a PSMA PET instead of a bone scan or conventional imaging.

We'll be in the position of, do we then go back and have to image them using conventional imaging, to decide what risk group they're going to be in?

I mean, I think we'll work this out over the next 3, 4, 5 years. For the current time, I think if we saw this patient and no bone scan would be obtained, we probably would go back and get a bone scan and make sure that they had low volume disease, from a conventional imaging standpoint, before deciding how to treat them.

I think that's ironic. We're going to depend on old imaging, because that's what our clinical trials, the rock that they rest on.

Alicia Morgans: That's such a good point, because high and low volume is entirely by those conventional imaging standards. In the setting of radiation to the primary, that really makes a big difference. Paul, what do you think?

Paul Nguyen: Yeah, absolutely. It's something that we think about all the time, is that when I look at somebody and I think about radiating their prostate, I look at conventional imaging. I want to make sure that they fit STAMPEDE criteria by conventional imaging.

Because I feel like it's not fair, necessarily, to exclude those patients from potentially life-enhancing radiation, just because the PSMA found more lesions than conventional imaging did.

Heather Jacene: Let me also just say, that I think that there's a chance, well, an opportunity with PSMA, that maybe there are more groups of patients within low volume and high volume, that potentially haven't really been explored and that PSMA PET is going to subdivide those groups, even to more risk groups.

Adam Kibel: Paul, are there studies where they've radiated the prostate, they have PSMA PET imaging and then PSMA PET imaging after they've radiated the prostate and saw what happened to the metastatic disease?

Paul Nguyen: You're talking about just radiate the prostate. So you're talking about, basically what STAMPEDE did, and did they follow it up with PETs? So, no. We don't really have that.

Adam Kibel: I would be think it would be really interesting to see what happened with the metastatic deposits, in patients that were treated with primary radiation.

I wouldn't be surprised if some of them shrunk. Not all them, but some of them.

Paul Nguyen: Yeah. That's certainly the hypothesis that radiation oncologists hold onto. We hope that part of the value of radiation and STAMPEDE Arm H was to stimulate some kind of immune response, that then could have some abscopal effect on the metastatic disease.

I think that that's why it's quite legitimate to do the randomized trial on whether surgery has the same effect and whether there could be something different. So, I think that's a very legitimate question. I'm glad that the trial is going on, to test whether surgery has the same effect.

Alicia Morgans: I agree. There's definitely so much to learn. Let's follow up on what we actually are going to do with this patient.

For Mr. XY, he decided to move forward with ADT and enzalutamide. This was for very low volume metastatic hormone-sensitive prostate cancer, because we did have that bone lesion that was quite far field in the skull. We had the pelvic lesion. We had, obviously those lymph node metastases, and so intensified ADT enzalutamide for that. Then we also layered on radiation to the prostate, per STAMPEDE.

Now, Paul, would love to hear your thoughts because obviously, STAMPEDE Arm H was ADT and radiation. This is really intensified systemic treatment with ADT and enzalutamide and radiation.

Paul Nguyen: Yeah, it's interesting. I feel like we're doing that a lot more commonly with these patients now. As you said, STAMPEDE taught us that if you add radiation to ADT alone, you get a survival benefit.

If you add abiraterone or abiraterone and enzalutamide to ADT alone, you get a survival benefit.

Now the question is, should we just do both? Isn't more better? I feel like, pretty much, that's what I'm seeing now, that we do tend to combine both of them for patients, even though technically, we don't know the answer yet.

Alicia Morgans: I would agree. We don't know the answer yet. We may get some information with things like PEACE-1. We're kind of looking at a kitchen sink approach, that's also going to include triplet therapy. So, that's really going to tell us quite a lot.

But I think, given the relatively good tolerability profile of the systemic therapy intensification and the relatively low toxicity of radiation to the primary prostate, we have just intensified in standard of care, without necessarily having the data.

I guess, time will tell whether this is going to be necessary or something that we're just doing because we can. The data remains gray in this area. But definitely, this is the way that many clinical practices are moving. Thank you guys so much, for talking through this case.

Adam Kibel: Pleasure.

Paul Nguyen: Thank you.

Heather Jacene: Thank you.

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