High-Risk Prostate Cancer: Diagnosis & Treatment Strategies

[Dr. Aditya Bagrodia]
Today, we're going to round things out with high-risk prostate cancer. Absolutely a pleasure. I thought it might just be helpful to get some basic definitions in there. High-risk, very high-risk when patients are coming to you. Who are we talking about here?

[Dr. Daniel Spratt]
I would say defining high-risk is a little easier as a larger bucket. We're talking to high grades of Gleason 8 to 10, or Grade group 4 or 5, PSAs over 20. Now, it's probably more in the MRI realm, but clinical T3, rarely we see these T4 patients. I think the value of very high-risk, and the definition used in NCCN is highly debatable. That's from a retrospective study, I think out of Hopkins that I don't think has a lot of clinical implications, and most of the guidelines say you treat them the same. There's been some newer definitions. People call the STAMPEDE very high-risk, which is PSAs over 40, high-grade T3, having two or more of those features, which may have some actual clinical implications.

[Dr. Aditya Bagrodia]
Totally. We'll definitely jump on into it, the primary pattern 5, the T4, things along those lines. Essentially, high PSAs, Grade group 4 and above, radiographic, something's at least got your attention, that's who we're talking about.

[Dr. Aditya Bagrodia]
Starting with patient intake, what are the critical elements here as you're starting to formulate what might be a best option for this patient? Maybe we could start with urinary symptoms, sexual health, things along those lines?

[Dr. Daniel Spratt]
I think probably for almost any man that you're potentially going to give a radical therapy to, we're going to want to know whether it's the AUA or IPSS, some type of irritative obstructive-type symptom assessment or an epic 26. Any rectal bowel movement, history challenges, Crohn's, ulcerative colitis, things of that nature, erectile function, of course. Even beyond that, I think it's also what's the priority for the patient. Some guys may have function, but it's just not a big priority depending on the significant other. Comorbid conditions, obesity, metabolic syndrome diabetes, heart disease. There's social factors, of course, to factor in also when talking about feasibility of treatment, where to get it, things like that.

[Dr. Aditya Bagrodia]
I think that priority element is actually quite important. I do mean it, but I almost have found that I tell every patient when they describe their sexual frequency patterns, I'll say, "That's totally normal," because I don't want people to feel weird about being sexually inactive or being sexually active at whatever frequency, whether or not they're able to have erections and so on and so forth. GI history, that's probably something that I don't think that urologists focus on, maybe quite as much. Ulcerative colitis, Crohn's disease, colonoscopies. Is this all mandatory intake?

[Dr. Daniel Spratt]
I would say so. It's been ingrained in me back in my training in New York at Sloan Kettering. I remember Michael Zelefsky telling me that every, we'll call it five years of his career, he's like, "Oh, maybe we'll try to do some radiation on this guy with Crohn's." Then he's like, "I learned my lesson again." While there's definitely cases I've done, especially now with the rectal spacers, and the accuracy of radiation, that's something that I would say, if it's active, even if it's a history, there's got to be a reason why we're starting with radiation therapy because that could be potentially catastrophic. We're talking fistulas, we're talking a lot of things. It's a little more complicated in high-risk. If it's ultra high-risk, and you know you have surgery, you may need post-op radiation at some point. Those are even larger fields. It's a conversation with the patient for sure.

[Dr. Aditya Bagrodia]
Obviously, we're talking about relatively infrequent cases, lower probability events, but they do pop up. By all means, if there's a patient, I think, from our end on the urology side that we know is going to be inclined towards radiation, getting that history, and getting a colonoscopy set up, I think is something we can do. Then you mentioned cardiac history. Obviously, that's going to have an impact on androgen deprivation therapy, and maybe which types of medications they would be best suited for. Family history, is this something that you're really dialing in on?

[Dr. Daniel Spratt]
We do a focused cancer family history. I think that once you're in the high-risk category, people typically start discussing, "Should you be doing germline testing?" I think when there's a family history combined with being high-risk, it's really something more to make sure that conversation is had then. Not that it's emergent, of course, it's just to start that conversation. Yes, their family history of breast, prostate, pancreas, colon, et cetera, but that's part of their standard intake for us.

[Dr. Aditya Bagrodia]
I'm curious just logistics-wise when I was at UT Southwestern, anybody with a family history of high-risk or intraductal, they went to go see cancer genetics. On a move to San Diego, mostly due to practice patterns, availability of clinical geneticists, we were actually starting to order the germline testing. It's nice because we've had a couple of trials for say high-risk patients that have BRCA mutation that can get neoadjuvant PARP inhibitor. What do you all do? Is it you that's ordering germline testing, or making the referrals, or typically the urologist one step ahead? How does that work at your institution?

[Dr. Daniel Spratt]
It's different here. I've been at UH Seidman at Case for about two years. I think that a lot of us end up sending off through one of the industry tests rather than an in-house assay. Most of the time, probably the most common is I tell patients just to go to color.com. Not that I'm endorsing them, but one of these tests, because it just goes straight to the patient's house, they pay $250, or whatever the going rate is for it. A lot of patients seem to prefer that because it's like they get the results to them. It's not ordered through the hospital where they get a blood draw on things, but that's how most of it-- I think probably many of us ordered a different assay. We're working on a more standardized, you could call it, germline risk, or these high-risk clinics to standardize it. We've got a couple of different that, I would say are the most common people are ordering.

[Dr. Aditya Bagrodia]
I like that. I don't have any vested interest in ordering vitae because we have a workflow. We also have this study called THE PROMISE study, which is cool. The patient gets a pamphlet, they create their own portal, they get sent out a saliva swab and their own results and they can figure out who to share it with. I like getting away for some of that paternalistic, your physician has to be the quarterback for everything.

[Dr. Aditya Bagrodia]
Lymph nodes, are you routinely rating them along with the prostate and the SVs or SVs, is that also part of your field?

[Dr. Daniel Spratt]
I always radiate full dose to the SVs. Especially in this PSMA PET era, the amount of isolated SV recurrences is just through the roof, but I actually typically do not radiate lymph nodes. I think that similar to the surgical trial data, and I know it's controversial of the benefit or lack of extended node dissection, it may be diagnostic, not therapeutic. We're not diagnostic by treating them. We're not gaining information. Again, if there's a recurrence in that node, you can give a nodal field later. I tend to, in most things, lead towards the side of quality of life. If it's T3B disease high grade or really high PSA or especially if it's node-positive, I definitely treat the lymph nodes, but run-of-the-mill Gleason PSA of 8 or 9, I wouldn't treat the nodes and just tell them that we really don't have fantastic data. We have one trial that's 250 patients that there's a benefit and multiple negative trials.