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 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 Genitor Urinary Radiation Oncology Group at Dana-Farber at 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. Our next patient, this is JL. Mr. JL is a 74 year old man with a past medical history of high risk localized prostate cancer, with a PSA of 54 in January 2021, an MRI with a PI-RADS five lesion on the right that was biopsied and demonstrated to be a Gleason 4+4 grade group four, prostate adenocarcinoma. This patient was treated with laser ablation for that lesion at an outside facility. At the time, it should be noted bone scan and CTs were negative. They were performed, but certainly not guaranteed to be negative at that time given the features of that cancer. The very soon follow up PSA there between August and November was 22, so a slight decline from a PSA of 54 down to 22, and in April of 2022, the PSA had increased to 79 from 22.

The patient, patient came in for a second opinion and case was reviewed in tumor board and imaging was reviewed. And so we will review that. We requested a repeat MRI of the prostate and a PSMA PET as well in those discussions, and we'll be able to review all of that imaging. I should also mention that because this patient had high risk disease, genetic testing was ordered and there were no targetable alterations identified. But germline genetic testing, of course is recommended for all patients with high risk localized disease or metastatic prostate cancer. And that is not necessarily based at all on family history or age of diagnosis, that's independent of those things. So it's for all patients with high risk, very high risk, localized disease and metastatic disease. But let's move on and see what we saw. Dr. Justine, can you show us the imaging results for this patient?

Heather Jacene: Sure, and I'm going to start with the MRI. So here we have the MRI of the prostate gland and then of the pelvis. In the prostate gland, we could see that there was this large lesion that was encompassing most of the right side of the gland. You can see it here on the T1 fat saturated image. There was also some extra prostatic extension. In addition, focally near the apex there was also another area of disease also with some extra capsular extension. In addition to this disease within the prostate gland, there was a large right operator lymph node that was also concerning for metastatic disease.

After the MRI, he proceeded to have a PSMA PET CT scan. On the mid we could see that there was some activity down here in the bladder, but also an area of increased intense uptake laterally, and then also inferior ally. So there was very intense PSMA uptake that correlated with the large lesion in the right side to the midline that was seen on the MRI here. In addition, there was intense PSMA uptake that was correlating to that right operator lymph node confirming metastatic disease. But then in addition to that, I'm going to zoom this in a little bit because as you scrolled up... I'm going to start up higher.

There was actually a very tiny three millimeter lymph node in this right common iliac area that had increased PSMA uptake. So anteriorly you can see the ureters, but this low level uptake in a very tiny node was concerning for an area of disease. And then as you scroll down a little bit further into... There was one additional area of uptake that also there were some lymph nodes again along this iliac chain, that were also concerning given that they were kind of in between that larger node and the smaller node that were pretty worrisome from metastases. So these are two small nodes, three to four millimeters that you would never call alone on a CT scan or an MRI because they don't meet, They're not really close that even to size criteria, no distant metastatic disease.

Alicia Morgans: Thank you for going through that. I'm glad there's no distant metastatic disease. I still feel a little bit frustrated or stressed for this patient who had a focal therapy, I think believing that this was going to eradicate the disease in his prostate. I wonder, Dr. Kibel, from your perspective, this was a high risk localized prostate cancer on a good day, it was bordering on being higher perhaps, but what are your thoughts about using focal therapies in this type of a setting?

Adam Kibel: I would argue very strongly against it. I think initial work was done in patients that had low risk prostate cancer, including work with lasers, as well as other focal therapies. And basically the patients all did well probably because they all had low risk disease. Increasingly we're exploring it in a favorable intermediate risk disease and maybe in a few patients with unfavorable intermediate risk disease. In that setting, it's important for patients to understand that this is not a treatment that has been shown to extend life expectancy. And while it makes a lot of sense that we'd be able to destroy the lesion and spare the patient having surgery or radiation, we still need to prove that's the case and I think we will. But I really don't know of anybody who is strongly advocating high risk prostate cancer being treated with a form of focal therapy. I mean, I think we all agree that whole gland therapy with surgery or radiation is really necessary in these patients that really have multifocal disease.

Alicia Morgans: I would love to hear, and we'll start with Dr. Nguyen on this, and then we'll get to you again Dr. Kibel. One of the things that worries me is that patients want to have- they gather a lot of information on their own, and they want to have the treatment that is the most personalized and the appropriate amount of treatment. Not over-treating, not under-treating. They just want to really, really kind of match that Goldilocks principle of getting just the right amount, so they have as few side effects as possible, but they do want to be cured.

And in this situation, I don't think that we would expect that he would have cured disease. He had some treatment, but it wasn't going to get rid of all of this disease. What I also worry about though, maybe not with this particular focal therapy, but with focal therapies in general, if they aren't treating the whole prostate, if they aren't clearing the disease, they can make things different so that it's harder in some settings to deliver additional therapies. That could be the case for SBRT, for example, or HIFU or whatever it is. And different therapies cause different effects that may then cause different troubles down the line. From your perspective, Dr. Nguyen, for this patient, would radiation still be an option if the patient wanted to get treatment, and are there limitations for different focal therapies that might change that answer?

Paul Nguyen: Yes. So a short answer I would say it is still an option, but with caveats and asterisks, I feel very sorry for a lot of our patients out there who, as you say, find information on the internet, and there's a lot out there. Some of it is frankly not proven and not true. And we have patients that are getting excited about whatever's the newest thing or the latest thing, and a lot of big claims are being made without the data to back it up. And I think especially, let's be clear, this patient was not treated with focal laser for high risk disease at our institution. But I think there are plenty of patients out there who are getting focal therapies for diseases where they shouldn't. And this is an inappropriate kind of thing. And the patients pay the price not only out of pocket, but also with their health and then with the side effects that they have to endure afterwards.

So this patient and patients, for example, who get let's say HIFU for high risk disease focally and then recur, we can treat them with radiation, but I find that the side effects are much more- substantial urinary toxicity. Also, there can be some risks to the rectum sometimes, but it's really the urinary where I find the most patients going into retention or having a lot of urethritis issues. So it's not a walk in the park. I think the promise that a lot of people are hearing about some of these focal therapies, especially for high risk disease like this, is like, Oh, don't worry. If it comes back you can still get radiation. But I've taken patients through this and it's not the same. It's not a walk in the park. There is a price to be paid on the back end.

Alicia Morgans: Thank you.

Adam Kibel: You also worry a little bit with high risk disease that there's a delay in treatment, and that delay in treatment actually can result in adverse outcomes. So you want to hit them with the best treatment early. And I mean there's a fantastic minimally invasive treatment for high risk prostate cancer, and that's called radiation. So if somebody really doesn't want to have surgery, or surgery is not a good idea, we have a proven modality that has been shown to extend life expectancy, and it's clearly minimally invasive and I wish more patients took advantage of it in this setting.

Paul Nguyen: Absolutely.

Alicia Morgans: Thank you. Thank you for that Dr. Kibel. And to that point, radiation is wonderful. So there's that point. But the other point that you made about delaying time to treatment and potentially having disease progression, Dr. Jacene, you pointed out two nodes that were very small. I don't think those would've been identified on conventional imaging because they didn't meet size criteria. So I don't think we would see those, but the obturator node probably would've been seen on that initial imaging if it was present. Is that true?

Heather Jacene: Yes, that certainly would meet size criteria on the CT scan. Now whether it was present on the original scans that he had at the time of the local therapy, we would have to get those images to go back and look. But really anything that's more than a centimeter would meet the size criteria and the short access, and should be worried about.

Alicia Morgans: So in this patient's case it seemed that probably developed after those initial scans, and since he had his initial treatment. And so it's just progression of that disease during that time period, which is unfortunate. So team, we have a urologist and a radiation oncologist, what do you guys think? Let's start with Dr. Kibel. What should we do for this patient?

Adam Kibel: I think he needs systemic therapy coupled with radiation. I think that, I don't want to steal Dr. Nguyen's thunder, but they're going to want to treat his pelvic lymph nodes, and I think the real question is just how high they want to go in using the radiation therapy. And I think he needs systemic therapy as well. And I would defer to my medical oncology colleagues such as yourself, Dr. Morgans, as what we'd want to use, but my guess will be some form of hormonal therapy.

Alicia Morgans: I would agree with that, but I'll let Dr. Nguyen answer first. What are your thoughts?

Paul Nguyen: Yeah, completely agree. This is a patient who now needs radiation. As I said, there will be more urinary toxicity here. We definitely want to treat the pelvic lymph nodes, and this is a great case of how PSMA PET can be so helpful in designing our fields. I think I might have mentioned that under the leadership of Dr. William Hall, there was an international group that was convened to look at PSMA PETs and how this might affect what kind of treatment fields we should be designing when we're treating pelvic nodes, because there's some nodes that show up on PSMA PET that we might not have included in our normal fields before. And so we've made those adjustments.

But for this particular case, you also see that there are certain areas of nodes that are showing up these kind of faint nodes where perhaps ordinarily we might not extend to, but now because of what we see on the PSMA PET, if I were treating this patient, I'd be very sure to contour those areas and make sure that all of them, and go wide and make sure all of that was in the field. So I think this would definitely be a case where the contouring and the treatment design is informed by the current PSMA findings.

Alicia Morgans: I would agree. And from a systemic treatment standpoint, we have nodal involvement. And so this is a patient where we're definitely going to want to do at least two years of ADT and add on Abiraterone for two years too based on that stamped data that we have, and really hope that the combination of that systemic therapy and radiation is going to get him a cure. Although this patient is very high risk and we'll have to see where things go. So let's see what ultimately happened to this patient. All right, so it looks like the team, our team really did pursue the same strategy that was discussed here tonight. So we decided to pursue external beam radiation to the prostate plus ADT and Abiraterone for at least two years and see how this patient does. So thank you all for walking through your thought process, and of course for reviewing the imaging with us today.