Chapters Transcript Focal Ablation Course: Surgical, Pharmacological, and Technological Advances in Urology So, so let me just ask, how many in the room uh perform uh focal therapy. OK, now, another question, how many would refer? A patient, a patient. Uh, that you felt might be appropriate for focal therapy, but you just don't, uh, haven't embraced the technology. OK, so there's uh that's an increasing, um. Uh, an increasing number now, so again, I began my prostate cancer journey as a, as a, a resident, uh, at the time, Doctor Walsh was sort of developing the concept of the nerve sparing, so I worked out the anatomy of the innervation uh to the, uh, of to the corpora, uh, and then he included me on the And nerve sparing, uh, a radical prostatectomy paper, uh, and that's sort of, uh, and if I look back at the first, uh, really 2025 years of my career, it really focused, uh, in radical prostatectomy and medical treatment of, of BPH. So I've looked at uh and published many of our outcomes following uh radical prostatectomy, and really our technical complications are, are less than 1 in 100. Um, in terms of continence, we've actually reported that if you use a single small pad over 24 hours, you consider yourself confident, uh, but that's different than being perfect, and I always differentiate that when I counsel patients. Uh, and so, uh, if we look at continence at 3 months, we're 70% and by 2 years, the good news is the overwhelming majority of men gain their continence. You know, we really do cheat when we talk about preservation of potency. Because we take the ideal patient, we take the patient who has perfect uh potency to begin with. And um uh we're gonna do a intended bilateral nerve sparing procedure uh and again, that's what we sort of publish as our outcomes and that's not the typical patient who may have ED to begin with but is functional. So I think we really have to really as well show um. Uh, in terms of when we talk about our potency and again in that cohort of men we've reported 65% preservation of potency. It's often uh uh under discussed with patients. We have climacturia, we have penile shortening and penile curvature. So I've always looked uh over the course of the 5000 radicals that I've performed this is what are the opportunities to improve our outcomes. I think one is to expedite recovery, although I think uh for the most part, we reported that half our patients are back to work at 2 weeks. Uh, and this is with the uh in terms of improved urinary continence, uh, to eliminate incontinence entirely or at least decrease the time to gain continence, improve, uh, sexual function, and decrease uh local recurrence and retreatment. Um, and so. You know, in terms of uh the, I'd have to say, and this train has left the station uh for probably the prior decade. I was always debating open versus robot. If you really look at the, the, the, the, the control trials, there really is no difference in terms of continence, potency, uh, and, and margins and then if you look at some of the uh lesser uh relevant outcomes such as length of stay. Um, and return to activities. There really is no valid benefit. So it really hasn't changed. It's changed the way we treat the disease, but it really hasn't changed the outcome. So the question is, uh, is focal therapy, uh, the option? Now, we, uh, I'd invite, uh, you to come, uh, in June. We do of course that that focuses on, um, advances uh in uh. Uh, in sort of screening, detection, and, and treatment of prostate cancer, and this comes from the first course, uh that uh we offered in 2010. This is the, uh, the old slot, uh, that the uh template that we use. So it was clear that focal therapy was not gonna improve disease control, that it could minimize incontinence and sexual dysfunction. Expedite recovery, but the real problem was uh having a reliable way of identifying clinically significant prostate cancer. So this is the case, and I often call it partial gland ablation, some call it focal therapy. This is what you, you, you have to believe. First of all, that the aggressiveness of prostate cancer is typically defined by the index tumor that's been shown. That the MRI identifies the index cancer in candidates for focal therapy. I'll show you our data in a moment that validates that, that the selection of candidates for focal therapy using MR fusion biopsy together with systematic biopsy rarely will significant cancer be outside of the uh ablation zone. That low risk in select cases of intermediate low risk disease are candidates uh for active surveillance so as long as we can effectively ablate the cancer uh that uh what is remaining in the prostate, which could be low risk disease or very low volume clinically significant prostate cancer, that uh the PTE trial has said we can follow these patients. That the focal therapy reliably destroys infield prostate cancer. We'll show you our data which is compelling. That preserving quality of life is a high priority for men with clinically localized prostate cancer. I think also that what we've learned from the Scandinavian uh uh prostate cancer trials, uh, is that the overwhelming majority of men. Do not benefit in terms of prostate cancer mortality or progression to metastasis and in fact if you look at the Scandinavian trials where they randomized to uh radical prostatectomy versus truly active surveillance and uh there was no crossover and if you develop metastases then you were treated with hormonal therapy that you had to actually do 9 radicals to prevent a mortality, you have to do 6 radicals to prevent the development of metastasis so you can see. That the there is clearly a treatment benefit, but the majority of men will actually live their lives without developing metastasis. Uh, and in fact when you looked at radical prostatectomy versus uh uh active surveillance, looked at mortality, 20% of men who had a radical died. Uh, and versus 30%, uh, who had the active surveillance. So that's where you get the 9 to 1. And if you looked at the development of metastases, it was 30% of men who had a radical and 45% who had metastasis, so that's where you get the, the, the, the 6 to 1. So when we're sort of looking at cancer control, uh, uh, versus uh functional outcomes, it's really important when we look at cancer control, the real relevant outcome, what we want to prevent is, uh, is metastasis or the uh or mortality. So this is one of the very early studies uh that I looked at, which at least for me as a prostate cancer surgeon said there's uh that we can reliably identify uh the significant prostate cancer in candidates for focal therapy. So, again, we looked at men who would meet our selection criteria. Uh, for focal therapy, but we looked at 59 of these candidates who had undergone a radical prostatectomy, so they all had MRI, they all had targeted with systematic biopsies. They had clinically significant cancer localized to uh uh one area of the, of the product. There's no extra capsular extension, uh, and so this would sort of be the cohort that we would feel would be a very reasonable. Candidates for focal therapy, so we then looked at the radical prostatectomy specimen and we looked to see how often will we see Gleason pattern for any Gleason pattern for uh out of the uh of the ablative field and we looked at that uh we found uh uh we defined clinically significant cancer as any. Grade group to uh a disease or Gleason pattern 4 and actually we found that any clinically significant cancer in 23% of the patients, but in all patients, the extent of the Gleason pattern 4 was less than a millimeter. Now, active surveillance is considered a very reasonable option and maybe even the preferred option uh for men who have low risk prostate cancer. So we and others have reported that in that cohort 40 to 50% of men have Gleason pattern 4 that we're actually following on active surveillance. So why can't we follow 23% if it's valid to follow, um, 40 to 50%? And also if you go back to the PE trial. Uh, 25% of those patients had had detected Gleason pattern 4 who were then, uh, randomized and in that cohort of 15 years of follow up, in fact, there was no greater progression, uh, there was no greater risk of prostate cancer mortality or uh or the development of metastasis in that group of men who had Gleason, uh, gray group 2 disease at the onset. So, so based upon this study, I felt that this clearly validated that as long as we do the MRI we do the targeted plus systematic biopsy uh with those selection uh criteria, uh, that it would be very reasonable uh to uh to offer vocal therapy. Um, uh, with the caveat that we would need active surveillance, but we would need active surveillance if you have a radical, uh, or if you had radiation therapy as well. So, you know, anytime we have a patient that we're counseling for prostate cancer, what we're really balancing is oncologic control, uh, and, uh, and, and quality of life. So, uh, the question is, is that, is there a group of men. Uh, where focal therapy really is a very reasonable option when you sort of consider these two competing, uh, factors. Look, you could probably cure most people with localized disease of radiation. You just fry the rectum and fry the bladder and fry the urethra, right? So there's always ways of trying to minimize the morbidity of radiation. So that's sort of with the also but uh maintaining a reasonable cancer the same thing with the radical prostatectomy, right? Uh, we spa nerves, we try to maximize the urethral continence mechanism and sometimes that's sort of balancing out functional and and onalagic outcomes. So since 2010 here at NYU, uh, those of us who perform uh focal therapy, we pretty much looked at the whole menu of, uh, of, of options. So actually in March of 2017, Jim Weisso and I said, OK, you know what, we're gonna set very rigorous selection criteria. We're gonna have a a a a consistent sort of a strategy for ablating the disease and we are going to have a very, very rigorous oncologic surveillance to see if uh focal therapy uh is at least conceptually based upon that study that we showed makes sense, but doesn't make sense uh in uh in practice. So we've actually enrolled over 500 men into this cohort. And initially, so, so the the enrollment criteria uh were a contralateral Gleason grade group one greater than one or distal apical disease or gross extra prosthetic extension were considered exclusions for uh for uh focal therapy. And as I said, the selection criteria, the functional assessment, oncologic surveillance were prospectively defined and standardized. Uh, and again, for, for Jim and I, we are cancer surgeons. Uh, so yes, we, we certainly wanted to uh improve functional outcomes, but we didn't really want to do this at the expense of, of cancer control. So the initial cohort, so now we have uh over 300 men. Who had uh pyres 2 to 5 lesions concordant with a unilateral intermediate r cancer. Uh, it could be Gleason grade group 2 or 3 that sort of met these, uh, inclusion criteria. And I'm also gonna talk about 54 men with a pyres 2 to 5 lesion concordant with low risk Gleason grade group 1, who we also offered, uh. Uh, focal therapy, so we sort of stratified, so initially we didn't want uh our um um uh critics to say ah they're treating all low risk disease so the first cohort that we published included only men with intermediate risk disease who for the most part would be candidates uh for radical prostatectomy or uh radiation. But I do believe there's a cohort of men with higher volume low risk disease which this makes an awful lot of sense. Uh, so the first study that Jim and I published, we said, OK, we are really gonna look to see if we are achieving oncologic control. So every patient, uh, at least the, the, the, the, the protocol was you're gonna get an MRI and you're gonna get a biopsy at 6 months, uh, to, uh, to, uh, a year. And we were really concerned more about local uh disease control of the index lesion, so we did 4 biopsies targeted into the ablation, so we took the pre-treatment MRI we actually segmented that uh on the post treatment MRI 4 biopsies into the target, 6 systematic biopsies, because we really wanted to see, you know, are we really controlling the disease? 98% of men. Uh, no, uh, Gleason gray group 2 or 3 outside of the ablation field. So we were pretty confident. That we actually were, were ablating uh the cancer. So then we, the next study was to publish our 3 year outcomes, uh, and in this group, we had 137 men, uh, again, all with intermediate risk disease with greater than 24 months of follow up. We actually had 104 follow their surveillance protocol and 27 were uh awaiting biopsy. And our compliance with the 2 year protocol biopsy was 75%. That's unprecedented if you look at the literature. If you look at the literature for focal therapy, most studies don't even have that level of compliance with a single biopsy, right? Uh, and we identified 14 patients that had clinically significant prostate cancer, but remember we're calling any pattern 4, Gleason pattern 4 a clinically significant, uh, cancer. However, of that group of 12, OK, um, 4 of those, the Gleason pattern 4 was less than 0.1 millimeters. And we felt very comfortable that those men could be followed with surveillance. 2 underwent a salvage radical, 1 salvage radiation. 5 underwent a salvage uh uh ablation, and 2, we advised to undergo whole gland treatment, uh, but they were noncompliant. And in fact, uh, uh, Ellie Rapaport is one of our uh residents, uh, who the good news is, uh, in his earlier life becom before coming to NYU, he ran a statistics company. Uh, so trust me, we've uh leveraged his, uh, statistical genius, uh, throughout the, the reporting of a lot of the data that you'll see. So now look at this. We're talking about the 3 year clinically significant prostate cancer free survival uh was uh uh 90 was 96%. And if we looked at time to detection of out of field, um, it was, well let me go back. This is, um, this is a time to detection of the right. So if you looked at the 2 to 3 years. The majority of those cancers that we were detecting were out of field. Right, but we knew we were gonna find some of those just based upon the fact that 20%. Uh, from our initial study, had clinically significant cancer that was undetected, but if you look at infield, we're still 96%. Uh, at 3 years, uh, out of field is 86%, and you know there's sort of this concept of, of, of treatment failure, so it's very interesting that we consider that a patient failed focal therapy if they go on to have whole gland treatment. Well, that's what they all would have had if we didn't have focal therapy, right? So why is that a failure when that would have been. The treatment they would have undergone if we didn't have focal therapy, but sticking with that. 97% of men at 3 years still had their prostates, or they weren't radiating. OK, so we're doing pretty well, right? So we just had our 5 year data published and let me tell you, the naysayers out there give us a lot of problems trying to get what is really impeccable data uh published because they just want focal therapy to go away. So now at 5 years we have 11% of men who are found to have any clinically significant recurrence and 14 were in field in 21. Uh, recurred out of field. So we're beginning to see still a very small percentage number of men develop in field, uh, recurrences. And so if we looked at our model which we call freedom, uh, uh, from in-field recurrence at 5 years, again, this is with a very high compliance with uh with biopsy, we have 86%, right? And if you look at out of field, that's 85% and if we now look at freedom from failure, we're at 91%. Now remember this is a group that has been imaged, biopsied with meticulous follow up and if you look at our 5 year data, 90% of our patients have undergone an MRI. We don't lose uh patience to follow up because uh we have my Linda and Viola who are right here, who will find you. They will find you, they will call you, they will harass you. Sort of, in a nice way, in their own, for their own benefit. So I will tell you, if you look at 5 year follow up in most studies, it may be 10, 20% at best, but this is with protocol MRI's. And if you look at the freedom from failure, it's, it's a 91%. So now at 5 years for guys who by I think anyone's criteria would be candidates for radical radiation, 91% still have their uh uh prostates or they haven't been radiated, you know, another 10% and we've done a, uh, uh, we've done a salvage ablation now. Most of, oh my goodness, this is terrible. You got 20% of your patients, uh, will have some clinically significant cancer at 5 years. This is how they validated the Gleason Gleason grade groups scoring system. So what you can see is this is after radical prostatectomy, disease recurrence, and if we look at 8 years, if you have a Gleason grade group 2 and you undergo a radical prostatectomy, your biochemical recurrence is 20%. You have a Gleason grade Group 3 is 40%. Now 1/4 of these patients had Gleason grade group 3. So why would we expect it to have absolutely no recurrences. When at 8 years, you got 30% of men recurring after a radical prostatectomy. So if you sort of look at this in context, it's actually looking pretty good. And again when we look back now at 5 years, uh, in terms of how these patients were uh were were managed, there was a subset of men that we continue to follow and as you can see, because they have very, very low uh risk, uh, or low volume Gleason pattern for, uh, and uh the majority ended up having a salvaged focal. Uh, and 11 of them, uh, underwent a whole gland foage which is 10% of the cohort, and I will tell you in retrospect. What we're observing is that many of those guys who failed had distal disease which were now less inclined to offer, uh, you know, the focal therapy. So again, one of the goals was to see can we achieve uh uh good oncological control which I'm convinced we shown how about the quality of life issues. So, uh again, another one of our residents, we call him Little Samir, uh but it's not S A M I R, it's S A N E E R, who I assume is here. It's not he's in trouble or he missed this big opportunity to get uh uh a shout out. So we looked at the 1st 100 men uh who had undergone the the uh the focal cryo, and we looked, how are we doing at 6 months? And what this is gonna highlight is how important it is when you look at outcomes to stratify according to their baseline function whether you're looking at lower urinary tract symptoms whether you're looking at uh at at sexual function and not a single patient. Reported any inconfidence for pad use, that's gone. Not a single patient had any rectal issues. That single patient got ADT. So now we're gonna look and this is again, it's a, it's, it's a busy slide. But what this shows is that if we simply look at the change in the IPSS uh uh for the cohort, there's only two symptom units and I go back to my BPH days. That's not a clinically significant outcome. But look what happens if you present with moderate or severe lower urinary tract symptoms, 8 to 18 or greater than 18. You actually have an 11 symptom unit change in the IPSS. So we showed that for radical prostatectomy and the ablation that we're doing. If you have a patient that like if they come in with moderate or severe luts, the chances are you're gonna actually reduce those luts in a clinically significant way. But again, because the majority of men don't present with luts. That's why when you look at the whole group, you can't make it better if you don't got it, right? And I've always looked at the radiation data, OK? And there's one thing what you look at is you see, OK, you look at the change in the sexual function in men undergoing surgery and radiation. And you notice that actually in the surgery group, it's significantly greater. But if you actually look at the baseline, there's a much higher percentage of men undergoing radiation who have significant ED and you can't make it worse. If you have ED to begin with, so what's very important is to really stratify your outcomes based upon their function and as you can see, if I look at the at the at the whole group, uh we do see a decrease uh in the in the in the SIM scores, right? And I think that is clinically uh uh significant, but what you notice, and I'll show you this in a moment, if you have really uh no ED to begin with. That incremental change doesn't have a functional consequence. If you got ED to begin with. No harm, right? But it's that group who I call they're sitting on the ED cliff, right? So many of the guys who come in, I'm, I'm on uh I'm dependent upon sildenafil, you know, I, I, I, my erections are sort of OK to begin with. That's the person who has a decrease in their functional outcomes where that can be clinically significant and we'll show you that here um uh in a moment. So now we look at the two year data. And you know when we do a radical prostatectomy if you looked at uh your sexual function post treatment at 6 months, it, it's pretty disheartening, but most will have the return of potency if they're getting it between 1 and 2 years and as you can see there is an incremental improvement between 6 months and a year and for the most part at a year, uh, I think that's where your return of function stabilizes and this sort of highlights that point. So the top plot is the patients who have no significant no ED to begin with, and you can see there's a drop, and then it sort of almost returns to baseline. Uh, and this is the group that you can reliably tell them that their erections are unlikely to be impacted. You look at the bottom group, right? These are the guys with EDB could be, so you really didn't have any adverse effect, and I do believe it's in that intermediate group, the group that would have sort of moderate ED you see there's a decrease, but those scores come back to about 1415, and, and that's the group I'm most uh concerned about now, uh, if we actually look at the preservation of, of potency and what we're basically saying this is sort of a. You know, not a very sophisticated uh uh analysis, but you go back and if you look at question two of the SIM index, and if they circle, you know, I can half the time or more, I can reliably have uh uh intercourse, then we say that those men are, are, are that we've that they're potent to begin with, and we use that as preserving the potency. So if we look at this. Uh, in our overall cohort of those men who who circle to or above, then 80% of those men at 2 years will have preservation of their potency. But if we look at those guys who had no ED to begin with, that's 96%. So whether you're treating patients surgical surgically with radical or radiation or focal therapy, you have to establish realistic expectations. And that realistic expectation uh is gonna be linked to their, their baseline uh function. So again, uh, let's look at low risk disease cause I've had when we do our June 4, I can't get Koperberg to say that any Gleason gray group one should be it should be treated with anything other than active surveillance, and I've showed him this slide. Uh, I'll show him another slide. I even threw in BRCA2, and I still can't get him to say that patient should not be followed with survey, and I'm gonna come back to the more details in this patient, but you can see this guy has a pyra's 5 MRI lesion, and as Samir said we biopsied the heck out of this thing, right? We did 6 cores and, and every one of those were positive. Uh, but all of those cores were Gleason grade group one, and, and I would look at this patient with this Pyres 5 to say that this is not a clinically insignificant prostate cancer. Look, it's already 2 centimeters, uh, in its dimension and may even begin to show some signs of extra capture uh extension. And I think one of the issues that we have with the active surveillance, and again this is the field that Stacy contributed a lot to, we don't have one, a, a consensus on how do you follow these patients and when do you rebiopsy these patients and the other issue is compliance and I think Stacy reported compliance with active surveillance biopsy is about 20 to 30%. So it's wonderful to say in the Canary trial or whatever how look here's the uh you know here is our uh progression and progression we caught it early enough where it didn't really have consequences but in the real world compliance is an issue so we took men who had higher we in other words, they all had an MRI lesion which means this isn't that incidental, you know, 5% of a biopsy cord that's Gleason gray group one that. Legitimately should be on active, so all of these guys had an MRI lesion. Uh, and now this is looking at the, the management of any clinically significant cancer, uh, and in 3, they had a salvage cryo, and 2, they underwent whole gland treatment. So if we actually look at freedom from failure from men with high volume, Gleason grade Group 1 is 96%. Now if you go back to the Hopkins cohort, and remember this is only Gleason-gray group one that we pulled out of their cohort. Um, but these could have been the guy who had that tiny little microscopic focus of low risk disease, not the volume that we're talking about. They actually had, uh, uh, 68% of men went on to hold gland treatment. So I do believe that at least from a cancer point of view, that treating selected cases of Gleason-grade group one with uh with focal therapy is very reasonable. So we just sent this paper in for uh a review. I'm sure we're gonna get to every which way to try to figure out what was wrong with this study, even though there's nothing wrong with this study. No ADT. Not a single patient ever used a pad. There was no treatment related regret. We did see in those men who had lower urinary tract symptoms, a clinically significant improvement. There was a change, uh, in the, in the shim and again 72% of the men had preservation of function, but remember we could still be dealing with that patient who's marginal who was functional. And because they're we didn't stratify here based upon their baseline so there is some impact uh on sexual function. So how do, so if you embrace vocal therapy, how do you follow these guys? So there's all of the consensus statements I recommend oncologic surveillance protocol that includes PSA, DRE, MRI, and biopsy, but there's no consensus on the timing. Uh, and unfortunately in 2024 there's no there's no prospective evidence validating any recommendation for how you follow the patient and you know the intensity of your testing and biopsy has to be dependent upon your rate of clinically significant prostate cancer. Look, if you do HIPU, uh, and in one year you have a 40% disease recurrence, you better follow those patients pretty carefully. You have the 3% recurrence when you biopsy everyone. Well, maybe you can sort of relax that oncologic uh surveillance. So this is the paper we also sent out to review. So again, If you want to look at the performance of MRI, you have to then biopsy every single patient, not only those who are MRI positive or negative. So this was the original cohort where we said if you have it, we're just gonna biopsy you independent of the MRI and what you can see, uh, is in this cohort at uh at 6 months in our series, only 4% had a positive MRI. And interestingly, uh, when we biopsied those guys, uh, we didn't find any cancer. So we began to say, well, you know, maybe what we can do is just not biopsy guys that have uh uh or biopsy everyone who has a negative MRI. But if you actually look at our 6 month data, uh, and again, realizing that almost every patient is gonna have a negative MRI. Uh, and when, and, and again, going back to that study, when we biopsied those guys who had a negative MRI, only 8% had clinically significant cancer. So if you think about it for a moment, you know, Samir sort of showed the data and said, well, you know what, everyone agrees that, you know what, if you have a pyrats too, you don't need a biopsy. Well, there's a 10% chance you're gonna have clinically significant cancer. But he said, OK, well that's acceptable because we don't want to biopsy that guy. Uh, similar if you get the biomarkers, right? And you get a 4K and it's uh less than 10%, you pretty much say, oh, you know, I probably don't have to biopsy that guy. So what I would say is at this rate of having a positive MRI. With a negative, uh, having a positive clinically significant cancer with a negative MRI is low enough that we feel comfortable abandoning a biopsy and I'm gonna show you some data because that would be an MRI invisible lesion. So now we go back and say, OK, well let's sort of see how this validates if we look at 238 men, uh, and if you had in this cohort, 6% of the men had a positive MRI. And you go, well, that's that's still pretty low. And of those guys, uh, we found that the majority, about half of them did have a positive biopsy. So we feel that again. The number of men that are gonna have a positive MRI is only 6%. So the question is, is that so low that even if half of those guys have a prostate cancer that we might, uh, that's clinically significant, that represents 1 in 30. So are we really, do we really even have to do an MRI at at all? And if you looked at those guys who had a negative MRI and Jim has a lower threshold for doing biopsies, uh, again, we didn't have any that were positive. So we actually don't biopsy men who have a negative MRI and you know, if you really listen to our data. We wouldn't do an MRI at all. But it's hard for us to do that uh in the first year. So now this is looking at 2 years. So now at 2 years, we find out that in that original cohort where we biopsied everybody independent of the MRI. Uh, we have 15% were positive. Well now we're starting to say, well, maybe that's getting to be a high enough, uh, likelihood of having a positive MRI to do it. Uh, and in that group, about a third of those patients had a positive biopsy. But now look at what happened in the negative MRI. Again, 10% of patients were positive for a clinically significant cancer. I think for many of us we've agreed that whether we're screening men. We can tolerate a 10% decrease uh in detection of, of significant cancers if we can avoid a lot of the morbidity of uh of of biopsy and then when we said, OK, let's look at the cohort where you didn't get a mandatory biopsy for a negative MRI, uh, again, it's pretty consistent that if you have a positive MRI, it was 16%. We had 15% in the original sample. And a third of those were positive. Uh, and again, if you look at the big cohort of men with a negative MRI, uh, it was 8% positive. So we actually have eliminated. We do the MRI but we don't do an obligatory biopsy. And now at 5 years here, where I'm getting a little uncertain. So again, um, we begin to what you see with increasing time, the likely of having a positive MRI increases. But the detection of significant cancer stays pretty constant. So now clearly at 5 years we get another MRI. Now when again, this is a sample that somehow it wasn't a reflex biopsy, it was sort of a for cause biopsy, although Jim has a very low threshold for a for cause biopsy, we now see 20% of those men have a significant cancer. So the, the, the question is, as we get to 5 years. Is that high enough that we should do the biopsy if you have a negative MRI? Maybe PET scanning may be helpful in identifying this cohort, uh, but for the most part, uh, I'm leaning towards getting a biopsy uh at 5 years even with a negative MRI. So this is the performance of the MRI for clinically significant cancer. The AUC is 0.59. It's really not that good, right? So a lot of men, uh, the majority of men who have a positive MRI don't have disease. Um, and, uh, our specificity, uh, is really quite good. Um, that's cause the majority of don't have a disease. So the rate of clinically significant cancer prior to one year is so low, that MRI and biopsy, I don't think are indicated. Uh, the rates of clinically significant cancer associated with a positive MRI, uh, justifies biopsying those men. The rate of positive MRI increases over time as we've shown. The rate of clinically significant cancer associated with a non-suspicious MRI at 6 and 12 months is less than 10%, and I think we can safely avoid a biopsy. We continue following those patients because as the mere suggested in the and the New England Journal article suggested, we're gonna find those patients along the way and you know at 5 years I, you know. Uh, uh, uh, I, I, I talked to the patient. I usually tell them, look, you can have a biopsy, you cannot have a biopsy. I got a kid in dental school, cost me $110,000 a year, so I like to do your biopsy, but I don't think we need to, so you choose. No one helps me pay the tuition, right? They all say, well, uh. Uh, I, I'll forgo the biopsy. So let's talk about MRI invisible disease and is it clinically significant? And you know what? This is gonna influence whether you do a systematic biopsy together with your MRI if you feel that whatever clinically significant disease that you're finding, which is Gleason pattern 4. Really isn't significant and it's gonna influence whether you're gonna do a biopsy after focal therapy if your MRI is negative. So now, as we keep increasing our series, we have 46 recurrences. So the question that the clinically significant, remember, any pattern 4, so what's the ratio of clinically significant disease if your MRI is visible or non-visible. Uh, what's the size and proportion of Gleason pattern 4 for MRI invisible versus invisible disease? What's the management of MRI invisible and MRI visible disease? And if you think about it, how many biopsies can we avoid, uh, if we don't biopsy, uh, MRI uh disease? So when we look at MRI visible, invisible, um. The majority of the cases are MRI visible, but the one thing is if you look at the very bottom of of the of the of the table, we're now saying, OK. How much pattern for? Are we actually seeing? In the MRI visible and invisible disease, so we just sort of pick 1 millimeter as a differentiator and, and what you can see um is that in terms of the MRI invisible disease. The majority of those patients are gonna have a lower volume of Gleason pattern uh uh 4. Now, this mere the validation is what did we do? Um, and Jesse is here is working on this paper and I think if we didn't have this conference, the paper would be sent out, um, but we had to break, uh, I had to let him sit and listen instead of work on the paper. Uh, but again, if you look at the patients who actually were treated with MRI who who had MRI invisible disease, half of those guys we followed. And why do we follow them? Because it was very low volume, unlike those who actually had MRI visible disease, they were much more likely to be to be treated. So at this point in time, I feel that the likelihood of finding disease if it's MRI invisible is low. The majority of those cases are gonna be very low volume clinically significant disease, and so I feel very, very, very comfortable, not uh not following, not, not uh biopsying those men who have a negative MRI now. How about PSA? We all use PSA to figure out. In active surveillance, but I would challenge anybody. And I haven't seen any single guideline that says, what are the criteria by which a PSA is gonna inform a decision of biopsy. Anyone wanna tell me how the, if it goes up once, it goes up twice, if it goes up this high, that high, so we all get PSA, right? But nobody has a way of interpreting that in terms of what are you gonna do with that data. Um, and so we looked at a group and Ellie's uh working on this paper. Um, where we said, OK, let's look at all the guys who had a, a pyres 2 to 5, and they had unilateral intermediate risk disease. Again, no distal apical disease, no clinically significant cancer contralaterally. They had at least one post, uh, uh, cryoablation, and they had at least 3 PSA measurements. So of these 188 men who fit sort of this criteria. They had 1951 PSA tests. They had 668 MRIs, so that's almost 5 MRI's per patient, OK? And they had 279 surveillance biopsies, which is almost 2 biopsies per patient, and we had 28 uh recurrences of significant cancer. Now, I will tell you that the only real meaningful parameter as far as PSA was having consistent changes in that PSA. So if we looked at the patients, we just looked at, you know, um looking at this as a continuous variable. OK, you can say uh the PSA velocity um was significant, but if you had two consecutive increases greater than 0.5, you had a 4 times greater likelihood of having clinically significant cancer. And if you had 3 consecutive rises, that's 15 times. So what we do use and we feel we'll capture some of those patients with maybe MRI invisible disease that's significant. We will biopsy you based upon MRI negative and a consistently increasing, um, you know, PSA. So our oncologic surveillance, OK, in general, your oncologic uh uh surveillance protocol should be depending upon what your rate of significant disease. All surgeons must rigorously assess their oncologic outcomes in the treatment cohort. And based upon what we think is uh probably the only medical evidence for any uh recommendation, but again this applies to our cohort is a PSA every 6 months, a progressively rising PSA is an independent indication for biopsy. MRI and biopsy, I think, are not indicated, at least for us that one prior to 1 year. That MRI should be performed at 2, 3.5, and 5 years, uh, always biopsy a positive MRI, uh, and I think the negative MRI, um, I feel comfortable following that patient in general. And I feel that the threshold for uh a biopsy would be the rising PSA. So, you know, in 2015. I think at one of our June courses, I said, here's what I, I'm confident the lesion will be successfully ablated. I'm confident there are no other clinically significant lesions. I'm uncertain whether clinically significant recurrences or new tumors will develop over the life expectancy. I was confident we don't burn bridges for future curative intervention, and I'm very uh confident there was no impact on confidence and potency. Now, I've softened that a little bit about potency, right? So how about today? This is an outpatient procedure and the 500 week done, we admitted one guy. Uh, and he was an 82 year old guy who developed a fit. Other than that, everyone's gone home. Uh, and I tell them catheter comes out in 3 days, you can return to work, and if you have a, if you're working at home, you can go work when you get home that afternoon. No incompetence, no rectal injury, and an improvement in lus when it's uh uh potentially clinically, um. It's a valid output. There is a significant reduction in semen volume, and you better tell the patient, you know, I'm sort of reminded of the story, right? Where the Jewish grandmother gets responsibility for following the kid, right? Takes the poor little kid to the beach, you know, it's really dressed up in a nice little suit with and all of a sudden this big way pushes the guy, the little kid out to the in the ocean, and she's praying and praying that the kid comes back cause that's all she can do. A big wave comes in there's the kid, and she looks up and said, where's his hat, right? So when the patient comes in and their cancers control their urinary symptoms are better, their potency hasn't been changed whatsoever, and they say, but doc, my semen volume of low. I always tell them that story, but now I tell them that story ahead of time because some patients. That will be uh an issue that men with moderate uh EED, they have the greatest potential impact on their potency that our whole gland treatment at 5 years for intermediate risk disease is 88%, low risk disease 96% then in and out of field recurrences for E risk disease is approximately 25% and often managed with surveillance or focal therapy. Uh, and again, we really do the, uh, all the for cause spots too. So I have no vested interest in whether men decide to do a radical or focal therapy. I love doing radicals. Um, I provide an evidence-based approach. In fact, I I give them our published data for both, and this is a sheer decision making. I would say 2/3 actually I would now say it's about 80% as we have more and more data evolving, right? What drives that decision to think about doing radiation, there's no ADT, right? Um, there's the total avoidance of inconfidence, there's improved sexual function, and I think it's the opportunity for salvage treatment. And here's what I believe and I don't have time to really address this because it's a whole lecture in and of itself. If the patient is inclined to do radiation, this has no impact on the morbidity of their radiation. I do believe it makes a radical harder. It makes it harder, but it doesn't make it sort of uh like a salvage radical after radiation. So I do think that it is a little, and especially if that disease was more apical. I think your apical dissection is uh is greater challenging. And so I would say in 2017, are we making the right decision? I had an awful lot of question marks. So now at 2014, uh, those question marks are uh are uh uh diminishing, and I think that the, the likelihood that we are gonna have and as long as they're followed that we're gonna have an adverse impact on development of metastases and uh mortality, I think is minimal and and we've had two patients. In 5 years that have gone on to develop metastasis, they all had negative disease in the prostate. So those were uh metastases that had preceded uh before their, their treatment. So I do believe, uh, and I know there's a few of you that I would, I would, I would encourage you all to learn the tech uh to, to, uh, if you're not gonna adapt this in your own practice to be, uh, to realize, I think that that it's, it's, it's potential implication. I think this is gonna be a game changer uh for prostate cancer and you're already hearing this sort of groundswell of taking intermediate risk disease and moving it into active surveillance. And I think this is the perfect option when you just feel that surveillance is too little. And a radical and radiation is just too much, and I think there's an awful lot of those patients with based upon the data that we have in terms of oncological and functional outcomes, that this is a very reasonable option. Now I have a few, I went over cause I knew I had an extra half hour, so let me go through a few uh a few cases and, and just while we're getting that up, uh, any, any questions that anybody has. And then usually when I do this in June, I walk around the room and I get all of you uh uh helping out, uh, but because of the limits of time, I'm just gonna go through and maybe uh uh 8 minutes, uh, uh, a couple cases, uh, and we'll see what we can get through. So, uh, this is a 64 year old gentle has an elevated PSA, um, it was at 4, so we had a 4K test, and Jim and I published that if you get a, if you look at the 4K and you look at a select MDX and you say at 10%, I'm gonna recommend a biopsy, 50% of the time there's a discordance between your recommendation if you're using the, the biomorpher. So in him because uh. Uh, he had a 4K of 15%. Uh, we did his MRI and interestingly, and I'll go through these quickly, he had a pyres 4, on the left anterior base and he had a pyret's 3, at the, uh, uh, at the, uh, on the right, and, and we did targeted biopsies 4 in each core, we did a systematic biopsy and it was negative. We published that if you have a pirate's fork. And you have a negative biopsy. You bring that patient back a year later. Do not just let him go into uh into uh uh uh uh an unstructured follow up. You bring that patient back 40% of the time the MRI lesion is gone because it wasn't cancer. 60% of the time it persists, and when it persists, 40% of those. Have significant disease because you missed it, right? So when that guy walks out of your office and you tell him his biopsy is negative, he actually has a 25% chance of having a significant cancer if it's gone. That's 0, right? Uh, so this guy, we brought him back. And interestingly, The 4 became a 3. And the 3 became a 4 and we were doing a study looking at PET imaging, and can that sort of help us uh in pyres for lesions that don't disappear? Can this help us identify um uh maybe that that 40% who have significant disease now we use axymen because PSMA wasn't available to us, but look what happened. The lesion in the left lights up like a Christmas tree, and it really wasn't much on the right, but the right side actually had the uh. Uh, the, uh, the significant disease two courses were positive for Gleason 2. we gave him all the options. Uh, he decided to do a focal therapy, um, and, uh, his PSA again, you can see it was 1.5, came down, then it went to 3.5. You get all excited, right? Back down to 2.3, back down to 2.2. Uh, and uh we did his MRI and in fact uh that left lesion. Has stabilized um and no lesion on the right, so we didn't biopsy him and uh uh I saw him now and he is 5 years, so look at his PSA 3.1, 2.2, I'm sorry, he's 4 years, 1.6. That's his last PSA. Um, and so he had a 3.5 year, uh, MRI that was negative, uh, and I don't know if I can congratulate him or not. He's 68, uh, he's on a second marriage and he's having a kid, so I don't know if they'll name it Herbert, I don't know, but uh. Probably not in these days, right? Um, so here's another I think interesting case, uh, this is the Asian gentleman, he's on the transplant list, um, and his PSA is 4252. He has a 4K it's 11%, right? Um, and so we get an MRI. This is the patient I showed you, uh, earlier on, and we biopsied the heck out of that lesion, uh, and all the cores were Gleason grade group one. Now, just like, you know, Stacey sort of talked about with genetic testing, it doesn't really change, you know, how you screen and how you treat. Actually, if you look at a, at a patient uh transplant patient, um, even, you know, they're gonna be on immunosuppression, uh, but it's felt that kid that that prostate cancer isn't really immunologic. Uh, and so in terms of your guidance for screening and treatment, it's really no different. Uh, than if they weren't a transplant patient. So this patient would have been a candidate for a focal therapy, which is what he decided to do. Um, and you know, we really blasted that lesion, uh, anteriorly and lo and behold, uh, his PSA goes down to 0.39, so that's pretty good from, from 5, and no change in his sexual function, uh, no urinary issues, um, and here is uh his uh post uh uh ablation which shows no new lesions. He actually undergoes a, a, a kidney transplant. Uh, and they get a, uh, a stricture, so Lee comes in and fixes it robotically. Now. He ended up, uh, as you can see, uh, and the MRI we did in in 2022, there was no uh recurrence. Uh, he has this, uh, a pyage too that I believe he had, uh, uh, uh, before, uh, and we, uh, continued to follow him. His MRI was unchanged, uh, except he had some enhancement, uh, in the, uh, uh, in the peripheral zone. Um, here's a fella, he's 61, his PSA was 6 in 2010-12, and 2016 it was 11. Uh, he had a nodule, um, and, uh, he had good sexual function and no luts. Uh, he had a a pyras 3, and I'll show you and we biopsied it. It was a Gleason gray group 1. And he had a systematic biopsy, uh, he had a tiny, uh, low risk cancer uh contralaterally. Uh, here is his MRI, um, and so I looked at that and said that you probably should do something about it, but surveillance probably too little, radical probably too much. Uh, I usually don't get biomarkers, uh, but we got an oncotype and it was more aggressive. Um, at that time we were just starting to do hyifu. We would never do hyifu on this anterior case, really in 2017 we moved almost mostly to to cryo because of cases like this, and uh his PSA went down. Now this is very interesting cause if you look and if you look at his MRI, he had like a non-enhancing ablation cavity in the left anterior transition zone, but I think they missed. Uh, a very early recurrence. We went ahead and did his biopsy because that was our protocol then, uh, and pretty aggressive biopsy, uh, and we didn't find anything, uh, and then, uh, we followed him and now if you look over here, you can see that's not just an enhancing lesion that also has a diffusion abnormality, um, and so we biopsied that and that was the only area that was positive. His ablation zone that was negative contralaterally, uh, he still had uh uh uh this tiny little low risk cancer contralaterally, which he had before, uh, and this time we did a repeat, uh, uh, we did a salvage cryo, uh, and as you can see this thing is gone, uh, and uh we, I think he's what, uh. 8 years following his his hai food, he's probably 5 years following his salvage cryo and his PSA is low. We just did his uh MRI. Um, I'm gonna show you one and then we're gonna finish it. This is an 80 year old guy, uh, and he ended up having this lesion looks pretty nasty. Uh, it was, uh, all cores were 4 + 3, so we went ahead and did his, uh, uh, ablation, uh, mainly cause he was 80, right? Uh, he did really well, his PSA went down, uh, his initial MRI looked good, uh, and then we started to see uh uh a uh. You know, the PSA was pretty stable, uh, but this is out of field, but on the right side, you can see he's developing, uh, another, uh, uh, a suggestion of a recurrence. Uh, he gets biopsy, he's a 4 + 3. you know, this was uh a bit distal, but we felt we can probably go ahead and do a cryo. We had him on for a cryo and he died of non, uh, uh, prostate cancer related, uh. So in fact, look what we did for this guy. He didn't have radiation, he didn't have hormones, he didn't have a radical, uh, and he died of, uh, uh, no cancer. Uh, that's it. So let's do this. Let's have, uh, we'll take a break. Uh, we'll come back, uh, in, uh, in about 1015 minutes, uh, and we're gonna have uh other opportunities to showcase uh our department with uh, our, uh, um. Uh, uh, radiation oncology with our, uh, uh, nuclear medicine and with medical oncology where we all work together. All right, listen, thanks. Published December 2, 2024 Created by Related Presenters Herbert Lepor, MD View full profile
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