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Gordon Brown: The next session is going to be on active surveillance for prostate cancer. It's going to be led by Dr. Ben Lowentritt. I guess Ben and the panel members would come up. Ben is currently the medical director of the Comprehensive Prostate Cancer Program and Director of Minimally Invasive Surgery and Robotics with Chesapeake Urology and has a leadership role obviously in United Urology. He's going to be joined on stage by Dr. David Morris, who is a urologist with Urologist Associates in Nashville, and he's currently the president of their group and the co-director for Advanced Therapeutics. He's actively engaged in prostate cancer research and running several large scale clinical trials, as well as Dr. Aaron Berger, who's a fellowship trained in minimally invasive surgery and robotics, and currently is part of the leadership team for associate urologic specialist and the chief medical officer. And he has a special interest in management of prostate cancer in both the localized as well as advanced disease states.

We have two other panelists. Dr. Ronney Abaza is a world-renowned urologic surgeon and roboticist. He's performed over 6,000 robotic surgeries. He's published over 120 peer-reviewed publications, has developed multiple novel surgical interventions for urologic cancers over his distinguished career and speaks widely both nationally and internationally on the management of folks with not only prostate cancer, but other genitourinary malignancies. Lastly, and certainly not least, is Dr. Dave Crawford who's an internationally recognized expert on prostate cancer with over 600 career publications, multiple book chapters. He's a professor at the University of California San Diego and currently has been widely recognized both nationally and internationally as an expert in men's health and prostate cancer in particular, and is named one of the top 20 urologists in the United States. We're very excited to hear what they have to say today about active surveillance and best practices for same.

Ben Lowentritt: Thank you very much, and thanks for inviting us here and I'm really happy to have this panel. My goal is to introduce some topics so that we can have a lot of discussion here as we go through and watch and learn along with everybody here. Thank you all for being here. I think just to introduce the topic, I think this is always a good topic to talk about, but it's a good time. The way that I think about this is that active surveillance, although it's certainly an option that's been around forever, really came into more active part of our discussion probably about 10 years ago, really in reaction to some extent both to data that was emerging and also to the USPSTF actions around screening. I think it's a really good time to try to get to those next level questions about how we're managing it today.

All right, thanks for the introductions. So this is going to be our patient with slight changes for the whole discussion. So a 62-year-old came in with a PSA of 6.3, that was a rise over a prior year and a half. Family history of prostate cancer in the father, though at age 67 a diagnosis and breast cancer in the father's sister who was 54 at diagnosis. The biopsy reveals Gleason Group one disease and a maximum of 40% of five out of 12 cores. The prostate measures 43 grams, which gives a PSA density just below 0.15. So first question to the group, and hopefully this is the easiest question of the day, would anyone not recommend AS, active surveillance? All right, good. So the NCCN actually has some really good language around this, and there was a little bit of controversy two years ago when they tried to change the language a little bit.

But the bottom line is for very low and low risk disease, the act of surveillance is the preferred treatment. There is a good amount of language, and you can read it here, about the fact that you certainly can allow people to choose treatment. This is a true example of shared decision-making in that a patient really shouldn't be making the decision to do active surveillance without understanding what that really means and what the other options are. If you read on here, and we'll get to this a little bit later, there's also some healthy discussion around favorable intermediate risk and specific ways, things that might technically put somebody in that favorable intermediate risk group but might give you a little bit more comfort in putting them on surveillance.

I think, and actually let me go back before you look too much. I'm curious to the group, what do you think, let's just stay with low risk, what percentage of patients do you think should be treated with AS? If we're evaluating ourselves and having good discussions with patients, what do you think is our target number? Is it a hundred percent? It can't ever be a hundred percent.

Ronney Abaza: I don't think you'll ever get to a hundred percent. Two-thirds.

Ben Lowentritt: Two thirds, okay.

Aaron Berger: That's a guess. Yeah, 75-80%.

Ben Lowentritt: Okay. I like 80, I like higher, I like better. But I'm just curious. It's an interesting point. It's just a target.

Ronney Abaza: I think it would be better rather than setting a percentage to actually look at the patient population and be able to actually create a metric for an individual practice and see what proportion of those patients are truly low risk and what are their PSA densities and how many percentage of cores and all of these other factors. Because I think it's a little bit too blunt of an instrument to just lump all of these people into one category and say that everybody should be at two thirds or three quarters or whatever.

Ben Lowentritt: I like that answer a lot actually.

David Morris: And you tried to trick us by throwing in the family history that suggests that they may have a BRCA mutation.

Ben Lowentritt: Well, of course. It has to have some discussion here. It's the goal. So when we look at AQUA, and I think a lot of our groups participate in the database. AQUA has shown an interesting and nice trend overall. It's small print, but the blue bar is this is all low risk prostate cancer patients, and the blue bar is the percentage that's going through active surveillance. And what you see in the people that are at least reporting to AQUA is that that number is approaching 60%, which is in the range of what we were discussing here as a goal. I don't think anyone feels like we're there yet as far as educating all of our colleagues, et cetera, and really also educating our patients to get them to accept that.

David Crawford: Ben?

Ben Lowentritt: Yeah?

David Crawford: Can we go back to that slide?

Ben Lowentritt: Yes.

David Crawford: I don't want to rain on this parade, but this is nothing to be proud of quite honestly. We don't want to find patients for active surveillance. We want to find people that need to mend it, need to be treated. This is craziness that we're very happy that we're seeing more active surveillance patients. This is an iatrogenic disease that we created by biopsying people that probably shouldn't have been biopsied. And when we first started doing biopsies, we weren't seeing those. A lot of this was related to PSA, and the most common cause for an elevated PSA size of the prostate, older men have bigger prostates, you find this, and then this led to the whole controversy and everything else like this.

I think we need to step back. This is treating the disease that it's already there. We want to go back and prevent us from getting patients for active surveillance. I want to see those numbers the other way. I want to see more people that are actually getting treated that we're biopsying, and there are ways to do it. I think we're going to talk about that in a couple of slides that you put in a little bit later.

Ben Lowentritt: No, it's a great point. I think that if you look at it as a percentage of the entirety of what we're diagnosing, you would expect it to plateau and hopefully come down because if we're not diagnosing the people that don't need to be diagnosed, I think it's a great point. I never expect Dr. Crawford not to rain on the parade or be controversial. We're really glad to have you here and speaking up. Some of the other efforts that are going on here, and I know Dr. Hafron is involved in this group in the MUSIC experience, they really looked at in the early adoption phase that they were seeing some early plateauing of adoption of active surveillance, put out some guidelines and how to actually incorporate this into a practice and saw really a catch up to that national trend or maybe surpassing it over time.

I think we do want to make sure that we're not over treating the cancer we're finding, and this is a testament to those efforts, but I think that's what we want to now start the discussion on. Within your groups or your departments, do you have a specific pathway, and how do you monitor that and how do you encourage those that are maybe not following it to get there? And hopefully we'll spend a little bit of time on this because I think this is really helpful for the audience.

Aaron Berger: Yeah, I can start. I think our pathway is nothing novel compared to most other pathways. It's amazingly based on NCCN guidelines. We do use data analytics. I think that's a key point in this because there's certainly just like any other patient in any disease state, but certainly prostate cancer, there's a lot of patients who do become lost to follow-up. As I tell all my patients going on active surveillance, your part of active surveillance is you have to actually come back. So if it's not an active surveillance, if you say, "Oh, this is low grade disease, we can just follow you," and they come back five years later and then you miss something, then they've got advanced disease now. So having whatever data platform you use to be able to say, "Okay, has the patient had a PSA within the last six to nine months? Have they had an MRI in the last two years?"

That really helps with adherence because certainly there is a wide variability with all things in prostate cancer amongst our colleagues who don't do it as often as many in this room. I think that's a key point is really having a way to keep track of these patients, make sure they're following up and aren't lost to followup.

Ronney Abaza: Yeah, I think of these three questions, the one that is the most intriguing to me is monitoring adherence because I think that's our worst nightmare. I had a couple of hours clinic before I got on the plane. Literally this morning I saw a guy who was diagnosed with Gleason six disease in 2018 and was sent to a surgeon for an opinion, the surgeon, said, "No, you should do surveillance." His interpretation of that was don't come back, just check your PSA, which he did with his primary care physician. So now he's coming back, and he's got an MRI and he's got a PI-RADS four with possible EPE. So it's exactly that nightmare scenario. I think one of the things that being part of a large group really enables you to do is to have a prostate cancer navigator. And I think that's really critical because patients need to understand that it's not, forget about it, don't worry about it, don't do anything, don't come back.

That active surveillance involves surveillance that you do need to follow up and you do need to be carefully monitored and assessed for progression because I think all of the series, when you look at the large data sets of active surveillance, if you follow these patients long enough, a large proportion of them are going to progress and have treatment. Dr. Crawford has done a lot of that work, so he can probably share that with us. So you can't just forget about these patients. I think in the real world that we live in, there's also a decent proportion of patients who are misidentified as being low risk right off the bat. And if they're not followed, those patients will not be identified and won't declare themselves as being actually intermediate or higher risk disease. I do about 400 prostatectomies a year, and I see it all the time.

I see the guys who have been on surveillance and progressed within a year, so you know they probably had that disease before. And then I see the other patients who meet all the criteria for surveillance but have some reason why they should have surgery like a lot of LUTS from a large prostate, for example, and then will actually find that, no, actually they had a much higher risk disease. I actually had one of my fellows, I hate to speak for so long on this, but I had one of my fellows five years ago look at our patients who would've met criteria for active surveillance but ended up choosing surgery for one reason or the other, and two thirds of them actually had Gleason seven and above, so we're intermediate or higher risk. I repeated that recently because now I figure we're in the MRI area probably catching a lot of these guys and identifying them as not really being low risk. It's actually now 73%.

So 73% of the patients that would've been candidates, PSA less than 10, Gleason six only, less than 50% of course actually had Gleason seven and above, 3% of them had positive notes. So those are the ones that scare you. And if we don't follow those patients, it doesn't mean that we can't put them initially on active surveillance, it just means that we have to follow them closely enough so that when they do declare themselves, we pull the trigger before they get too far.

David Morris: And hence the reason they took preferred out of the NCCN guidelines a few years ago. I'd love to say that we have a perfect protocol. We paid a lot of attention to this as a group seven, eight years ago when no one was using active surveillance. That was like my call to arms joining the practices is we need to do better. So we did a lot of genomic testing to push the idea of no one dying from this even if they leave it alone. And so then our uptake really rose, and then honestly, we left it to all the shepherds to manage their flock, and we became hands off. Now our anxiety is more of tracking patients to make sure that they're actually coming back for clinic visits, which is a bigger issue. But at some point, I have to trust my partners to read NCCN guidelines and do the right thing. I'm not trying to handhold the practice through managing active surveillance now that we have a greater than 50% uptake in low risk.

Ben Lowentritt: Anything to add?

David Crawford: I think you have to look at facts to make decisions. And there are a couple issues here. One, is you've had somebody delivered to you that has a low grade cancer and you want to do active surveillance, and two of you already said that a lot of those men undergoes some sort of treatment at least by 10 years, and it's a significant number. The facts are this. We looked at some 900 patients that underwent our mapping biopsy program a number of years ago that came in that were candidates for active surveillance. And we found something very similar that you did with radical prostatectomies is that almost 35% of them had badness. So they had at Gleason seven or eight and nines and tens that were missed. So right off the deck, you got that many people. Then you have the whole thing about active surveillance, we'll talk about markers to help, is selection of people for active surveillance.

How many of you have done a radical prostatectomy on somebody and the biopsies were positive on the right, and when you took the prostate out, the tumor was on the left. Anybody raise their hand? Okay, what does that tell you right away? It tells you about how we're doing these biopsies, and we can be missing things and we can be in the wrong side. And that's what really bothers me about targeted therapy too unless you really know where the target is. So the thing of it is is that what are we going to do with it? How do you follow it? You can do anything you want. You can get an MRI that was in favor for a while. MRIs, the other thing is is they miss high grade cancers at the lowest 5% to 7%, at the highest 25%.

And so we've got all these variables that are there, and I think it hearkens back to is we've got to rethink this whole thing, and we have the tools to find people that need to be treated. And PSA is a great test. We trash it. It's a net you throw out, you want to catch the big fish, let the little ones go away. We have ways to do that right now, and we do that in medicine. If you go into your family practice doctor and your blood sugar's elevated or your PSA's elevated, they don't start you on metformin or insulin, they do an A1C hemoglobin. We should start thinking about our A1C hemoglobins. We have them out there. We have molecular tests that help us get to there.

And the other thing, these tests are helpful in following people. If somebody has a low grade cancer and you're following them, what do you want to find? You want to find that 30% that have badness. So some of these lot of tests like the SelectMDx, and so a number of the other ones will tell you your risk of having high grade cancer, ProstateNext test and a whole bunch of them. So I just think we've got to rethink this whole thing. And, again, I don't want to perseverate on it, but not be proud of the fact we're seeing more active surveillance.

Ben Lowentritt: I want to continue on that discussion because this was the testing and what's available now either in tissue testing but also in urine and blood testing as well. I just threw up some questions in here. You don't have to feel obligated to answer these directly, but how do you find, I think as you stated, David, they were often used to help get people comfortable, both the doctors and the patients early on, but are you still finding them as helpful, the tissue-based testing, the prognostic tests? Are there other tests that are evaluating? Do you think it helps the doctor more or the patient? Is there something in a research standpoint that you'd like to see specifically in the AS population once they're on AS that may help you? I'm just curious, the current state of some of these tests, not necessarily specific to each test, but just what you're looking for and what might be helpful going forward.

Ronney Abaza: I think with any of the genomic marker tests, whichever one you choose, personally, I think all these patients who are going for surveillance should be offered to do genomic testing. Now, for non-Medicare patients, maybe there's a financial barrier they don't want to deal with or things like that. But otherwise, I think it does have value for everybody depending on which test you're using. I think if you do a test and you have a low risk patient and whichever test you're using comes back and says, "Yes, this is low risk," I think the patient and us feel better that we're doing the right thing. If you have some discrepancy where it's coming back high risk or this patient is not a candidate for surveillance, then I think it certainly is going to create some anxiety for the patient. And then you have to deal with discussing that with them saying, "Hey, we maybe don't need to move forward with treatment right now based on just this one test, but we maybe need to have a little bit quicker finger on the trigger for doing a confirmatory biopsy or repeat imaging or whatever."

I think there definitely is a role for the genomic testing. Which one you choose is certainly a personal preference. Some of you seem to have some more emerging data that are better than others, but I think it is important for everybody. But in some of the tissue testing like looking for the cancer field testing, I think that's a test we've used somewhat with various degrees of success. If that comes back positive, then I rarely will have a patient that says, "Oh, yeah, I'll come right back in for another biopsy." But, again, it's another marker to say if we do need to do another biopsy, this was left apex was showing up positive, let's focus on that area a bit more.

But I think all these tests, and going back to Dr. Crawford's point earlier, we do have a lot of tools available, whether in the prebiopsy space or in the potential AS surveillance space to use. And obviously we don't want to just use a bunch of expensive tests just to use them, but if you have a protocol and you have value and there's decent data to back it up, I am sure patients would rather have a blood test, urine test, genomic marker based on their tissue that's already present rather than having to go back for multiple repeat biopsies, which no one enjoys, even if it's with anesthesia, they're still having symptoms afterwards.

David Crawford: I think that the acceptance of a lot of these molecular markers by urologist has been very slow compared to other specialties, melanoma, things like that where they use markers. So why is it? Are urologists dumb? I don't know. It's hard to move off of what we've been doing and do new things, but there are markers here that help us. You say, "Well, if they have just two areas of Gleason six and 5% and they don't need Polaris, Oncotype or things like that, I don't buy that because, again, the biopsies are random, and they only get 0.5% of the prostate. We have markers that help us. Polaris and Oncotype are very good ones here, and there are also some other markers that are out there and new ones that are out there to help us.

But we've got to get in our heads that these are not pregnancy tests. They're not black and white, they're a data point. So you got this data point, that data point, that one, and you make a decision. Everything's not going to be right. When I give talks on markers, people come up to me always afterwards and say, "Hey, well I did this marker and this guy had a Gleason 10 and he died." Well, it happens, and nothing's perfect.

Ronney Abaza: So my routine prior to the MRI era was that I would do an immediate confirmatory biopsy because the vast majority of patients who would be coming to see me had a biopsy done elsewhere. And as Dr. Crawford said, there's variable reliability of those biopsies. So I used to do an immediate confirmatory biopsy. Now that we have MRIs, my routine for the patient that is seeing me, that first consultation with low risk disease, is to do the MRI if they haven't already had it as well as a genomic test. My preference is Decipher, but they're all good. So I routinely will do a genomic test, an MRI, and then if those are both favorable, we put them on surveillance.

Ben Lowentritt: Did you want to add anything?

David Morris: I'm honestly moving most of my tissue testing away from the active surveillance discussion and more towards what Spratt got to earlier, which is more predictive in terms of intensity of treatment as we get to the more intermediate risk disease. I think the ship has sailed. If you're Gleason six, I'm comfortable with active surveillance. I understand that we're missing some significant cancer that's there, but those people have also been in the active surveillance cohorts that have been followed forever. And as Cooperberg would probably argue with you, those people still survive active surveillance, and we still catch them and do delayed definitive therapy on them. And many of them we capture. And the reality is, prostate cancer just moves slowly enough in most people, thankfully, that we can be dumb urologists and still do okay. So most of my tissue testings move past AS. It's more about intensification. I think the genomic tests that you're alluding to would be great. Who do we need to biopsy to find the high risk disease and maybe skip finding some of the low risk disease?

Ben Lowentritt: I think my only personal thing on this is if we had more understanding of a test that would show a change over time, that would be really concerning beyond PSA. And I think although a lot have focused on this initial decision for AS, we're just starting to see decent data about people we're monitoring on surveillance, where I think that's where the consternation really comes in. I'm going to change up the case just a little bit. Same patient, except there's one little difference here. Now this is Gleason group two, right? So you're now talking about favorable intermediate risk. All the other details are the same. Anyone not comfortable starting that patient on active surveillance?

Ronney Abaza: So the one piece of information we don't have is is, how healthy is this guy? What's his life expectancy?

Ben Lowentritt: Healthy otherwise.

Ronney Abaza: I think all of those factors should take into account. And like you said at the beginning, it's a shared decision with the patient. So it's not that you wouldn't offer it to him, discuss it with him, but within the context of what his treatment goals are, his life expectancy, health, et cetera.

David Morris: You may not encourage it, but you would certainly offer it.

Ronney Abaza You'd bring it up and explain to them what they could expect with different options and let them decide.

Ben Lowentritt: All right, I'm just going to change up a little bit more. Now the patient's a 53-year-old, same details, Gleason group two. Does that change your discussion? I know you just said maybe you don't encourage, but you allow or you add it and make sure it's on the list. I think that's an interesting way to put about it. What about this patient?

Ronney Abaza I think there's two buckets of people that go into active surveillance. There's the guys who are going into active surveillance because they're probably going to die of something else first and never have to do anything about their prostate cancer, and I think that's the vast majority of them. And then there are the other guys who just don't want to do something now, and they just want to kick the can down the road until maybe they have a young fiance and they're planning to get married. Whatever it is. There's some reason why they're really not interested in treatment right now, and there's no urgency for them to have treatment even if they're 54 or whatever this guy is.

I would explain to them from that perspective. I'd say, "Look, you're young and healthy enough that you're probably going to live another 20, 30 years. Is this a cancer that you're never going to have to treat in your lifetime?" Probably not, but is it urgent, doesn't have to be done now? No. So if you wanted to do surveillance for a period of time and see what happens, it's not unreasonable. And, again, I would be doing the MRI, the genomic testing, the belt and suspenders just to be sure that that isn't unreasonable for him.

David Crawford: One of the things that going back, does everybody agree with the second line with the family history and breast cancer and some sort of dramatic germline testing should be done?

David Morris: I would test them. I'm imagining that along with other genomic testing. That might be something that would push me to take active surveillance off the table. Personally, I would have someone with BRCA on active surveillance. The Philadelphia Consortium basically said there's no reason you have to treat those people, but I would follow them more closely.

David Crawford: Yeah, watch more closely.

David Morris: And definitely delayed intervention is more the sales pitch than you're never going to have to do anything.

David Crawford: And there's another bridge between, even though I'm against that, finding patients for active surveillance, when it happens, it happens, and then you got to do something about it. So that's where we're talking about how you follow and things like that. One of the things, and I'm sure this will come up, is there's a bridge between radical prostatectomy and radiation. And that's treating the lesion targeted focal therapy. And if you're sitting on an MRI and all these other tests and now people are getting PSMA tests and so forth, it's all about knowing your target. And this is the problem I have with focal therapy is not knowing the target, but if you know the target, it's an easy thing on this guy now, and it's very acceptable to do things like HIFU, cryo and all the other things you have out there.

I've done a lot of those over the last 15, 20 years, but what I'm finding now are those people like this that I did 10 years ago are coming back with nothing where I treat it but on the other side. I've got two people I'm seeing next week in San Diego that I took care of 10 and 12 years ago that now have been on the other side. So do you do radical radiation on them or do you use HIFU or cryo or something? That's what I'm going to do.

David Morris: But that was a successful kick down the road.

David Crawford: It was. They came in to see me, and that's what we decided to do.

David Morris: Have another cycle of focal therapy.

Ben Lowentritt: I guess it gets to the question is, in the interim, what had you been doing or what had someone been doing and have they been monitored? Is this just new disease because they're 12 years older or is this unrecognized disease that progressed? It sounds like it's probably the former.

David Crawford: I think we've all seen men that have had radical prostatectomies 20 years ago with undetectable PSAs that are now going up. If you've been around long enough, you do, you see them. There's something weird about the disease, how it's in abeyance or how long it takes to get to the point where their PSA goes up.

Ben Lowentritt: So just some interesting data also to come out of MUSIC, and this was their adoption of active surveillance and favorable intermediate risk. And you see it's approaching 50% in recent years, which is pretty remarkable, I think, overall as far as hopefully that means that they're being monitored closely, et cetera. And you can see that over time, over the five to six year period, the center top is treatment-free survival, so essentially patients that are getting treatment are falling off. And then below that is broken down between the Gleason group one and Gleason group two still in the favorable intermediate risk overall stratification and the purple being the group one, so they're less likely to come off over time.

And then the top right is an interesting one because it's really more of an outcome. It's talking about biochemical recurrence in patients that have either an immediate radical prostatectomy or those that went through at least a period of active surveillance with favorable intermediate risk disease and then were treated eventually with radical prostatectomy and then went on to have BCR. So you do see there's an increased incidence of biochemical recurrence happening in those patients over time. And that's going to be something we're going to have to understand. Does that really mean that there's going to be a long-term bad outcome or have you kicked the can down along the road that this is just BCR that's not going to have a consequence? I think that's really where some of the next level data is going to be.

I think we've talked about a number of these things, but just very specifically when you're talking about your favorable intermediate risk or maybe low volume unfavorable or any intermediate risk patients, and people suggest this already, are you choosing different ways to monitor them?

Ronney Abaza: Well, the first question, the patients that you choose for these are going to be, at least in my experience, older, sicker patients. So older, sicker patients, shorter life expectancy, those are the ones that are going to be the more reasonable for favorable intermediate risk and active surveillance. So in those cases, you may not have to monitor those patients as closely because you know that they're probably going to die of something else first. So it's a spectrum, of course. So, for example, you have a 75-year-old guy who's had multiple heart attacks and strokes and can barely walk around. Does that guy need to have a biopsy every couple of years and an MRI every so often and whatever? Probably not.

Ben Lowentritt: Actually, this is a great point. So in your practices, do you differentiate between watchful waiting and active surveillance?

Ronney Abaza: Yes.

Ben Lowentritt: Because you're describing to me a watchful waiting patient that I'm going to say, "Okay, we didn't find high grade disease, let's put this aside, and unless your PSA shoots up, we're going to agree that we're not going to follow this aggressively." So I think that's a great point to bring up here. Depends on why you're doing the biopsy. We should be purposeful in why we're doing biopsies. I think that's a really good point to what Dr. Crawford said and then react. But increasingly, I have younger patients with low volume three plus four asking to not do anything. I guess the question is, should we be watching them differently?

Aaron Berger: Well, I guess the question that comes up then is, as we've talked about, there's not great adoption amongst many urologists, many of our colleagues. I'm sure there's those that will see a new consult for elevated PSA, not even repeat a repeat PSA, let alone do a biomarker test. I think we have to, in some ways, keep it consistent. In our practice, we've not really separated out let's do one way of surveillance for Gleason six, one way for favorable intermediate and just try to keep it simple for everybody so it's the same protocol. I think that adherence to that's going to be a lot better. Are you checking PSA or maybe doing MRI a little bit more often than you need to on Gleason six patients? Probably. But if you are catching people who are progressing with favorable intermediate risk or even those who have Gleason six that something was just missed in the first place, I think keeping it simple and consistent for all those patients just makes more sense, at least in my mind.

Ben Lowentritt: We're catching up on time here. So I want to get to a couple of the last points first. So this patient that was the 62-year-old with three plus four went on surveillance. Now, after a year on surveillance, the PSA has gone up marginally over almost a point, has a follow-up MRI that has a PI-RADS four lesion that wasn't seen a year prior, now has grade group two in that target and up to five out of 12 of the systematic cores up to 30%, pattern four from 10%. Now, I didn't stress this before, but are you all looking at the percent of pattern four in your biopsies critically? To me, that's actually been one of the big things I've changed in my practice is understanding the value of that number.

We saw a presentation at this meeting two years ago or whenever it was from Scott Igner, and it shows a really good correlation. But the real question then becomes, and I think this is a critical point for us to spend a couple of minutes on if we can, is when do we recommend coming off of surveillance and going on to treatment? I think this is where there's all the consternation and the risk of delay is maybe real.

David Morris: I tend to recommend no changes just based on PSA alone.

Ben Lowentritt: So no changes in treatment, but maybe drive a biopsy?

David Morris: PSA would drive something else, whether it's an MRI or a biopsy, but typically not straight to treatment if I can avoid it.

Ben Lowentritt: And we talked a little bit about some of the different diagnostic tests that should be able to be used here. I'm not sure there's great data yet to say which one should be used in this type of situation. Would you get an MRI and then go straight to treatment or would you always do a biopsy based off the MRI?

Ronney Abaza: Again, it's a discussion with the patient. The MRI many times, like, again, the guy I saw today, I offered him, if you want to stay on surveillance, at least we got to do a biopsy because you've got probable EPE. They're even saying it might be in the seminal vesical. So if you're interested in continuing surveillance, let's do a fusion biopsy and go after that. The alternative would be that your PSA has gone up pretty dramatically. You've got this MRI. If you want to just go ahead and have treatment, that's another option as well. So it's a discussion with the patient. And, again, you've got to have that backdrop of how old is the patient, what's their health, what's their life expectancy? You wouldn't have that discussion with somebody who's on their last leg obviously.

David Crawford: That's the art of medicine. And some patients say, "I've had it. I don't want any more biopsies. Take it out, Doc. I've had fun with this." This is something that AI isn't going to solve for us, believe it or not. The last thing I got to get in before we get pulled off the stage here is I think there's a role for five ARIs in these patients. We were going to discuss that because what drives them crazy is their PSA going up from BPH, and we know that it can't have some facts and prevention.

Ben Lowentritt: I put this on our last slide for you.

David Crawford: Yeah, I know.

Ben Lowentritt: It's a softball. That question of PSA management I think is a real one. Is there a specific finding on biopsy? Is it number of cores, amount of Gleason four? Is there any one thing or it really just feeds into the bigger picture?

Aaron Berger: Yes.

Ben Lowentritt: Okay. All right. I really appreciate everyone's time. Thank you very much and everyone's attention. This will continue to go on as a discussion because these patients hopefully are going to live a long time on surveillance.