Alicia Morgans: Hi, I'm so excited to be joining everyone with the team from Dana-Farber for our GU Prostate Cancer Tumor Board. My name's Alicia Morgans and I'm a GU Medical Oncologist at Dana-Farber, where we all work collaboratively to care for these patients. Let's introduce ourselves starting with Dr. Kibel.

Adam Kibel: I am Adam Kibel. I'm the Chief of Urology at the Brigham and Women's Hospital and also the Dana-Farber Cancer Institute.

Alicia Morgans: Great. Thank you. Dr. Nguyen?

Paul Nguyen: Hi, I'm Paul Nguyen. I'm the leader of the Genitourinary Radiation Oncology Group at Dana-Farber and Brigham.

Alicia Morgans: And last but not least, Dr. Jacene.

Heather Jacene: Hi everyone, I'm Heather Jacene. I'm the clinical director of Nuclear Medicine and Molecular Imaging.

Alicia Morgans: Wonderful. Let's get started. So let's talk about patient AQ. Mr. AQ is a 65-year-old man with a history of stage IV marginal zone lymphoma who presented for an evaluation by our team. In December of 2021, he had a PSA of 4.53, followed up in January of 2022 with a PSA of 4.49. Given the persistent elevation, he underwent an MRI of the prostate in March of 2022, that was an incomplete study due to claustrophobia, but they were able to identify multiple partially imaged enlarged lymph nodes in the pelvis, and they did recommend a CT scan which they hoped he could tolerate. In April of 2022, he had a CT of the abdomen and pelvis that demonstrated splenomegaly and enlarged lymph nodes that had progressed in size since his last imaging for lymphoma in February of 2018. And he did have some chronic prostatomegaly.

In May of 2022, he had a prostate biopsy that was notable for Gleason 3+4=7, Grade Group 2 disease on the left, and Gleason 3+3=6, grade group one prostate adenocarcinoma on the right. He was referred for an opinion regarding his prostate cancer. He had been followed and is still followed at Dana-Farber for his lymphoma. His imaging was reviewed and was notable for that lymph node enlargement. And so we really came together to think about how to work through his case today. Reviewing that, of course, in Tumor Board. I should say that a PSMA PET was ordered after he was seen by medical oncology to really give some better information to the Tumor Board discussion. Dr. Jacene, can you share with us what we found?

Heather Jacene: Sure. So this is Mr. AQ's PSMA PET CT scan. You can see on this maximum intensity projection image, a lot of normal physiologic biodistribution of the tracer. There's not a lot of abnormal or intense uptake showing up on this image. If we start from the top and we scroll through, it looks physiologic, and then as you come down, this is all physiologic in the parotid glands, in salivary glands. On the CT scan, we can start to see that there are many cervical lymph nodes that are notable, some of them for their size, but also for their number. The PSMA uptake in these lymph nodes is low level, about the same as the blood pool. As you continue down into the mediastinum, there are some calcified nodes, not a lot of axillary lymph nodes.

As we keep scrolling, his spleen is enlarged with some heterogeneous PSMA uptake. There is physiologic uptake in the kidneys, the liver. Also, as we keep scrolling down, then you can start to see some enlarged left retroperitoneal lymph nodes all the way down to the iliac chain on the left. There's also some on the right. And as we keep scrolling further, there are more lymph nodes in the pelvis. The intense activity are the ureters. The lymph nodes have lower levels of uptake. Some external iliac nodes on both sides, again with low levels of PSMA uptake. So lymph nodes above and below the diaphragm with low PSMA uptake than when we look specifically at the prostate gland. The prostate gland is enlarged. There's some heterogenous PSMA uptake, but nothing that was really focal within the glands to definitely note where the prostate cancer that had previously been biopsied was.

So overall with the lymph nodes above and below the diaphragm with lower levels of uptake, we were worried that these lymph nodes could more likely be related to the lymphoma rather than prostate cancer.

Alicia Morgans: Great. Thank you for walking us through that. I would say there was actually a lot of discussion before we ordered this. So when I saw him in clinic, I reached out to his lymphoma oncologist too, just to make sure that we weren't getting extra scans just to get them, because I had a feeling we would need to do a biopsy either way to get tissue confirmation of whether we were dealing with metastatic prostate cancer or potentially just enlargement of nodes from his lymphoma, which was at least equally possible, if not more so.

And so the reason that we ended up ordering this scan is because we wanted to see if there was any area of nodal involvement that had a particularly high PSMA expression and would suggest that if we biopsy in that location, we might have a higher likelihood of getting prostate cancer. It's not uncommon that we face these kinds of questions in lymphoma and we usually biopsy, but it's nice to know that there might be a modality out there, this imaging modality that can help us direct our biopsies. Now in this situation, as you mentioned Dr. Jacene, it's all a relatively low level of uptake. So, Heather, from your perspective, is there anything that you would say is really the place to target or is it really relatively similar in terms of the lymph node uptake and so we could kind of just go with the most accessible safest area?

Heather Jacene: In this particular case, I think that the approach of trying to find uptake that was differential to biopsy is a good one. We do that all of the time in lymphoma itself to look for higher grades of lymphoma versus lower grades of lymphoma to guide the biopsy. So the approach was good. Just in this particular case, the uptake was pretty homogeneously low. So really here targeting the most accessible node to biopsy, that might change the management if something's further away or closer. So the prostate gland seemed to be the most reasonable thing for this particular patient.

Alicia Morgans: Thank you. Thank you for that. And I wonder from your perspective, Dr. Kibel, when you see a patient like this who is a potential surgical candidate, has this comorbid lymphoma and these lymph nodes, if you could confirm that this is likely localized disease, is this the patient that you would feel could potentially be a surgical candidate?

Adam Kibel: Yeah, I think they are. I think the critical question is how aggressive the lymphoma is. So what's really nice is being a institution where you have world-class liquid tumor specialists and they can give us an idea of whether this is something that is an acute illness, an acute disease that needs to be managed more aggressively, or whether it's something that can wait while we manage the prostate cancer.

Alicia Morgans: Yes, and good point. So always important to understand, especially if we're dealing with a second malignancy or in this case the first malignancy and now prostate cancer is the next or second malignancy, what's the risk from each of these malignancies? In this case, his marginal zone lymphoma is something that, whether it's in the nodes or not is relatively conservatively managed with a life expectancy that is still years and years and years. So luckily this is not an imminently life-threatening lymphoma that needs to be treated immediately and is something that is being monitored and we can focus on prostate cancer care in this situation, which is helpful.

Dr. Nguyen, I think from a radiation oncology perspective, I wonder what your thoughts are if this patient had prostate cancer throughout these nodes, we may decide that this is not necessarily a case that's best served with surgery and, of course, that's something that we might debate. But from your perspective, if there was prostate cancer in these nodes, if this was the situation and, of course, he would go from localized disease to maybe more locally advanced disease, is this a setting where you might consider radiation and perhaps some intensified systemic therapy still with a good, hopefully disease control sort of outcome or potentially even treat this patient with curative intent?

Paul Nguyen: Yeah, definitely. I would agree that if this patient had nodes positive from prostate cancer, would definitely favor radiation as the first choice. Based on the STAMPEDE study now, we can intensify with abiraterone and improve overall survival for these patients. And so I definitely would favor in that setting with a node positive radiation to the pelvis and the prostate abiraterone for a couple of years and definitely with curative intent. We can dose intensify any of those lymph nodes that are positive. We've got great targeting now that can do this with relatively minimal toxicity to the GI tract. So I think it's the best option for these patients when they're node positive.

Alicia Morgans: That makes sense.

Adam Kibel: Well, can I ask you a question about that?

Paul Nguyen: Yeah, bring it on.

Adam Kibel: Is the location of the nodes important in deciding whether or not the patient will benefit from radiation? So I can't imagine that supraclavicular lymph nodes are ones that you'd be advocating radiation. But is there a boundary point at which you say, look, this is a disease where radiation therapy doesn't have an impact or a number of nodes where that doesn't have an impact?

Paul Nguyen: Yeah, it's a great question, Adam. So certainly patients who are considered N1, which would be classic pelvic lymph nodes, I think all those patients are fair game for treatment. I think that as we have PSMA PET, we start to see that those lymph nodes can start to creep higher and higher and higher. We might not have seen them before. And the question is how high do you go? As a radiation oncologist, I find that it does start to get more toxic as we get close to the lower border of the kidneys. So as we kind of get around to that sort of like L3, L2/L1 area, you start to have a lot more toxicity because now you're getting close to the kidneys which are a very sensitive organ.

But I have treated young patients up to that level, even if they have disease there, trying to maximize the possibility of curing. We're really stretching it, I would say at that point as we're getting up to that level. And I have seen many of these patients recur and sometimes they'll recur right above the field, which is very frustrating. And so somebody who's got classic pelvic lymph nodes, I feel great about radiating them. But you're right, Adam, there is a point where as you keep going higher and higher and higher, at some point we're really dealing with true metastatic disease and we may not be helping patients as much as we think. So where to draw the line, younger patients I'm willing to treat higher. As patients get older and more frail, I'm less willing to treat as the nodes get very high.

Adam Kibel: Thank you.

Alicia Morgans: I would say that this is definitely an area of active investigation. There will be a STAMPEDE study that I believe is opening hopefully within the next six to 12 months that is really assessing radiation to oligo metastatic sites in a large, very low volume type metastatic hormone-sensitive population. There is so much interest in this particular population and the fact that it is growing rapidly as we're integrating PSMA PET into our localized disease staging for these high-risk patients that I do think that we will have answers that will help us in the future with some data, but it is an area of high interest. And as all of us know, I think, we're already changing our treatment decisions based on these findings, which is really, I think fascinating and so hopefully helpful to patients. Any other comments here before we move on?

Heather Jacene: I think I'll just make one more comment on the prostate gland itself because this is an example of a case with a patient who had, I guess lower levels of Gleason score, there was a Gleason, I think three 3+3=6, and the 7 was a 3+4. And so that probably goes along with the literature showing less PSMA uptake in those lower-grade lesions compared to those that are 4+3 and then higher where most of the literature actually is. So it's an example of that as well.

Adam Kibel: One thing I find very interesting is there don't appear to be a lot of false positives with PSMA PET. By that I mean other diseases that we falsely identify. There are some though. Could you tell us which those are?

Heather Jacene: Sure. The list I think keeps on growing as we do more scans, but I think the ones that I've seen and are most published, any tumors that have a lot of, there's PSMA and neovasculature, and ones that are fairly common, renal cell cancers, you can see them on thyroid cancers, you can see them in glioblastomas. And so the list, I think keeps growing. Again, as I said, that we see more. But in those tumor types, it's more related to the tumor neovasculature rather than the expression of the PSMA on the tumor itself. But also non tumors like sarcoidosis has also been reported, other things like fractures, benign bone lesions, meningiomas. So, the list keeps growing.

Adam Kibel: What's interesting is none of them that you've mentioned are in the lymph nodes or in the bones. So if you see something in the lymph nodes or the bones, you can feel fairly convinced that it is indeed prostate cancer.

Heather Jacene: I think so. And I think in those situations it's really important to have a discussion with the multidisciplinary team because if you see something that's not fitting the pattern of the typical spread of what that prostate cancer will be, trying to figure out if it could be another tumor is a very good thing to do, especially when the clinical picture and the imaging findings are not congruent with each other.

Adam Kibel: Thank you.

Alicia Morgans: Yes, thank you. Well, let's move on and we'll find out what happened to this patient.

For this patient, we pursued biopsy of a left retroperitoneal lymph node. And the reason here is that this was easily accessible, was going to be a safe area to biopsy, and we thought that we could get a high yield there and there was no lymph node that really distinguished itself as having an especially high PSMA expression. We found involvement by a B-cell lymphoproliferative disorder that was comprised mainly of monocytoid appearing lymphocytes occurring in sheets and it had IHC, or immunohistochemistry, that was consistent with marginal zone lymphoma, which, of course, is the lymphoma that this patient already had.

So given that and, of course, the intermediate risk localized disease that we had already identified in the prostate, we really felt that the lymph node involvement was consistently going to be lymphoma. And so the patient's actually proceeding with a prostatectomy in about a month for his favorable intermediate risk localized disease. So thank you for your time on this case, guys.