Fernando Bianco: Everything I'm going to talk about today we are doing it in the office, but it could be done easily in the ASC, as well. Some have advantages of doing it there and some have advantages of doing it in the office. In the office, when we do this we use no anesthesia other than local, or nitrous, or a combination of both. And since July, we use a sufentanil, which is sublingual along with the local aesthetic. So the rationale for focal therapy is many, and starts with the three randomized trials showing no real benefit of overall survival or cancer specific survival associated with surgery or radiation versus observation. And the other fact that we know that most men that go into the surveillance protocols will drift away and go into either surgery or radiation, just a matter of time.

So by 2012, about 10 years ago, about one out of nine men were showing up with prostate cancer in the form of metastatic disease. And then the guidelines in 2012 didn't make this better, it actually made it worse. And we published a paper note in the incremental rates in metastatic disease that were already being seen by 2018. And by now, there's several reports now showing that about two out of 10 men. So we had an increment of 10, of 100%, over the last 10 years in the emergence of metastatic disease at the time of diagnosis. So prostate cancer in general has been always shrouded by uncertainty because of the many ways that we do the biopsies. And there is this principle by Einstein that says that insanity is doing the same thing over and over and expecting to see several results. So 10 years ago we challenged ourselves and we started our focal therapy program, or targeted therapy program, as a way to respond to this form of management. A wide ample protocol focusing in outcomes such as conversion to surgery or radiation, emergence of metastatic disease, and reincorporating people depending on their age.

This was the first patient I treated back in 2013. And we currently have and experienced over 1500 procedures done in the office setting. And this is the typical curve in PSA. What you see and eventually you have to deal with their [inaudible] as it grows over time. Fortunately, we're not alone. If you look at the literature in focal therapy over the last five to seven years, we have an incremental number of papers showing in reports, showing the benefits that could be associated with focal therapy. And there's different forms of energy that can be applied. One of the critical questions is always, what's focal therapy and how it's defined? And we do MR fusion targeted therapy. That's our modality, but there's many others in the literature and this will be growing over the next years to come. Whether it's a hockey stick or Hemi ablation, et cetera. The arsenal, it's growing as well. So currently in the office we're able to do cryoablation targeted, as well as laser ablation, either for cancer or BPH. And in the ASC you can do HIFU, you can do IRE.

And there's many technologies coming, such as coil radiofrequency, water ablation, nano-particles, and even to cut. So one of the things that's going to help with glucose, urologists parts of glucose, basically what you're seeing on the screen, which is AI driven readings of MRIs. And these are six separate patients read by AR platform, which we work with that they do this report in less than three minutes. And this is a tool that will be available for radiologists, but also for us in the office as we try to do a better job into identifying where the regions of interests are. And then focusing in sampling those, as well as random in a transperineal fashion because that's the way we should be doing biopsies nowadays. Anyway, one of the things that we achieve is certainty.

So we have precise knowledge of where we take in those samples. So we can go back into the same spot. We will know where are the cancers individualized by, where the samples were taken. And based on where they're positive and negative, we can then devise plans so we can go and target these lesions and limit the collateral damage that usually goes with it. And I think that as this rose over time, we're going to have a role for immunotherapy, molecular markers, and also genetic studies that will be driven where the multifocal of the tumors are, rather than just taking the worst cancer. This is a short clip that shows the local anesthesia technique and how we do it. We essentially, freeze it. We kind of numb the skin and then we use lidocaine, about 10 ccs on each side of their rough edge to really achieve the block.

And then we complimented it with a block for the neurovascular bundles. We used the grid because the grid allows for math and precision when you put the needles in. And that's great when you use infusion and registration software. So after we block the bundles, then it's easy. And you have done the registration to go to the precise spot where you need to be so you can achieve the ablation that you want, without guessing and in a short period of time. Most of our procedures for cryo last about an hour. This is due to the freezing and thawing process. Most of the procedures we do when it's laser, lasts less than 20 minutes. So you can see patients in between while you're doing this, or do a biopsy, or other things. Anyway, so this is an example. This is another case from a phase one study that we just completed on laser ablation.

And again, once you are in the fusion environment, you just go ahead and it's like playing a video game. You have your coordinates that there will be on the left lower quadrant of the screen, you can see it. And then using the grid, you go to those spots, and it's usually within five millimeters that you can go ahead and then put your troker in, and then advance the laser fiber. And one of the things we found is that you can use the seven watts energy and apply it directly there, for about three and a half minutes. That will give you about 1800 JUULs. That's all you need for each application. And you can do it sequentially, so you don't need to use many fibers and basically, save costs. With the laser, you see those bubbles like it's showing in the screen. So what are the results and what's out there? Well, Laurie Klotz really did a great job during the pandemic putting together a series of studies and compiling over 5,000 patients on different forms of energy.

Here, the data for laser is basically done in bore, inside the MRI machine. And what I showed you before is really the first study taking it out. But what we see with focal therapy is that the rates of incontinence are low. Arguably, they should be zero. But again, this has to do with the definition. The rates of erectile dysfunction are pretty low. They're under 20% for most men, and they preserve ejaculation. Then, the cancer control rates are pretty good. Now, other adverse events like fistulas that we talk about, that's usually associated with whole gland treatment, not really partial gland ablation. Urinary tract infection can occur and they occur because of the catheter, as well as retention because of the size of the gland. But most importantly, the results are pretty homogeneous in general. They're coming in and basically showing that rates of conversion to surgery radiation are low. As the freedom from re-treatment or for conversion, remains high.

Anyway, this in that patient that I quickly show you that video, this is how it looks. This is how it looks immediately after we performed the laser ablation. And then at three months... And then, sorry, at a month. And then at three months, you could see that the prostate has shrunk already by three months to 80% of the original size. And the PSA had dropped dramatically, as you can see it over there. There's other data coming out in cryo patients, this series from USC. Short term outcomes show the freedom from need of either re-treatment, or conversion to surgery, or radiation, or initiation of hormonal therapy, or METS. And that is related as well to the risk in this case, using NCCN guidelines and also to the PSA level you choose to treat your patients. So obviously, those who have PSAs less than 10 are the ones that benefit the most. And arguably those that are more mostly indicated for this form of therapy.

Importantly, the adverse event profiles are very low as well, and are quite tolerable. Most of the complications tend to be grade one. Particular urinary retention tends to be one, again, when the prostate is big or occasional UTI, but nothing really major. And by three months most patients have recovered their erections to where they are, sometimes they lose the transient leap because of the inflammation, and they should be continent. This is how it looks on MRI after an interior HEMI ablation, essentially. This is our data here on 874 patients that we analyzed this year early. Breaking it down by Gleason and looking into conversion to either surgery, or radiation, or whole gland cryoablation. And the PSA seems to have arose mostly experimental, nowadays. Both of these patients, you really need to do an MRI at a year and probably a biopsy as well.

But depending on how fast it dropped and how the slope is, it will give an indication of a patient who's been successfully treated or not. The average reduction in this paper done with using HIFU patients, over 1300 of them was about 73% in the PSA when we look at that over time. And that also corresponds to the probability of failure. In our own series, the average drop is again 73%. So it ranges around in the inter quartile ranges, you could see it over there. Very important to have to get an MRI a year later. We recommend to do a biopsy. We were doing it compulsively up to 2019 when we saw this data for the first time that basically told us that, if the piRADS apply to the non-treated prostate and the absence of enhancement on the treated prostate, then you could spare doing the biopsy because the rates were so low.

And anything that looks from a three to a five, then should have a biopsy. So what about reimbursement? I think the fact that focal therapy has arrived is noted by Medicare. And all the payers are really starting to pay for this technology. So this shows the reimbursement for the facility fees. There's a series of C codes that have been approved for irreversible electro operation for laser for Tulsa, which is intraurethral HIFU. And you can see the rates over there. A little bit lower for ASC, roughly about 70% of what they pay in the hospital. The physician fees then change because when you charge a C code, then the physicians have to charge the patients when they do it in the ambulatory or in the hospital. Now, in the office, when you submit those payments, then you get a global. And when you get that global, then depending on your own cost structure, that's how this works.

So cryo is fully reimbursed, it has a code. Laser with a C code is being reimbursed, I'll say about 70% of the time at the moment. And you always compliment with the MR guidance. So when you do fusion biopsies though, however, doing it in the ambulatory may be a little bit beneficial because you get better reimbursement. There's no real economic stimuli for transparent needle fusion biopsies, but its great care along with it. So what I tell patients really is that tumors will be destroyed, that the quality of life will improve because the urinary function improves in about 70% of them. That they're very limited, very limited risk in terms of erectile dysfunction. And most importantly that they're not burning any bridges, that all the options are there. You're just bringing new cards to the table. And I want to close with this.

Back when I was a resident and going into a fellow there at Memorial, the big thing was open prostatectomy and that's what we were dreaming to do. But the robot was coming and I lived it firsthand in Detroit, as I saw the rise of the Henry Ford program under the leadership of Dr. [inaudible]. But I believe that now with robotic surgeries at the peak, and there's really little innovation we can do that other than what we showed today with AAC cases and things of that sort. But focal therapy is the emergent paradigm, and it's going to come and I think we have to be ready for that. Thank you very much. Everybody has an open invitation to come to Miami. That's my email, if you have any questions. And again, thank you Dr. Shore and Dr. [inaudible] for allowing me to be here.