Faculty: Ardeshir Rastinehad, Arvin George and Fernando Bianco

Moderators: Tom Polascik


Art R. Rastinehad D.O.

Northwell Health’s System Director for Prostate Cancer at the Cancer Institute

Vice Chair of Urology at Lenox Hill Hospital

Art Rastinehad, D.O. joined the faculty at Northwell Health in January 2020.  He is the Northwell Health’s System Director for Prostate Cancer at the Cancer Institute and the Vice Chair of Urology at Lenox Hill Hospital.  He trained at the National Cancer Institute as an Interventional Urologic Oncologist and is the first urologist to be dual fellowship trained in Urologic Oncology and Interventional Radiology. He has expertise in a wide array of interventional radiological and surgical techniques, including image guided procedures, prostate artery embolization, laparoscopic and robotic surgery. 

Dr. Rastinehad’s prostate cancer team has now incorporated state-of-the-art imaging to help visualize suspicious areas in the prostate for cancer. Dr. Rastinehad has also authored and implemented clinical trials of new techniques in the diagnosis and treatment of localized prostate cancer. In 2011 at Northwell Heath, he was the principle investigator for a Phase III clinical trial using MRI/Ultrasound fusion technology to improve prostate biopsy techniques.  Using information from the prostate MRI, we can now target specific areas to better diagnose and quantify a patient’s prostate cancer. This was the first trial of this technology in the United States outside the National Institutes of Health.

This new clinical approach is helping to lay a foundation for the evaluation of a new technique, Focal Therapy, which only treats the diseased portion of the prostate.  As of May 2016, Dr Rastinehad was the first in the world to perform a gold nano-particle directed ablation using an transperineal MR US Fusion guided focal therapy system.  Dr Rastinehad and his team recently published the first series using this new technology in Proceedings of the National Academy of Science (PNAS).

For more information, please visit www.interventionalurology.com

Arvin George, MD

Assistant Professor, Urology

Arvin George, MD is a Urologic Surgeon specializing in the diagnosis and management of genitourinary cancers.  After obtaining his medical degree from the Royal College of Surgeons in Ireland, he completed his Urology Residency at the Smith Institute for Urology, Hofstra North Shore-LIJ School of Medicine.  He remained to complete his Endourology fellowship in New York gaining additional subspecialty expertise in robotic, laparoscopic, and percutaneous surgery.  Subsequently, he completed a Urologic Oncology fellowship at the National Cancer Institute, National Institutes of Health.  Dr. George’s clinical practice includes both surgical and non-operative management of prostate, kidney, ureteral, testicular, and bladder cancers.  Dr. George’s research interests include minimally invasive and image-guided treatments, functional prostate imaging and focal therapy for prostate cancer. 

Dr Fernando Bianco

MD from Universidad Central de Venezuela

Urology Residency at Wayne State University in Detroit 

Fellowship I. urological Oncology @ Memorial Sloan Kettering Cancer Center NY

Director of Urologic Oncology at GW university and relocated to Miami where as Associate Professor of Urology for Columbia University he co-funded and served as director of Robotic Surgery program for Columbia University in Miami Beach before moving on as a founder of non for profit Urological Research Network in Miami Lakes

Has over 100 peer reviewed contributions and currently serves as Professor of Urology- NOVA Southeastern University and Investigator in-Chief of Urological Research Network

Started Focal therapy program in 2013

Thomas J. Polascik, MD FACS

Thomas J. Polascik, MD FACS is Professor of Surgery, Duke University Medical Center. He is the Director of Surgical Technology, Duke Prostate and Urological Cancer Center. He is the founder and co-director of the International Symposium on Focal Therapy and Imaging of Prostate and Kidney Cancer that began at Duke in 2008. Dr Polascik is the Editor of the text Imaging and Focal Therapy of Early Prostate Cancer. He currently is the founder and President of the Focal Therapy Society, Duke’s Director of the Society of Urologic Oncology fellowship training program and the Genitourinary Program on Focal Therapy at the Duke Cancer Institute.  He is the Medical Director of Duke Men’s Health Initiative Screening event each September and is a governing member of several medical boards and societies. His clinical and research interests focus on prostate and kidney cancer. He has authored over 350 peer-reviewed manuscripts and book chapters.

 

Webinar Transcript

Dr. Jared Winoker:

First, I'd like to thank everyone for being here. On behalf of the Endourology Society and the Focal Therapy Society, we'd like to welcome you to the least installments of the masterclass in endourology. It's really been a wonderful educational initiative thus far, and we'd like to thank Varian Medical Systems for their grant and support of this educational activity today.

Dr. Jared Winoker:

So today promises to be a very interesting discussion on focal therapy. Specifically, we're going to be focusing on how to start a focal therapy program, and really who better to disgust the intricacies of this topic than the all-star panel of thought leaders you see before you? We're privileged to have them all with us today. Please do keep in mind that today's webinar along with all previous and future sessions are being recorded, and they're going to be available on the endourology.org website. Simply go ahead and select on the homepage, follow to the education tab, and then select on masterclass.

Dr. Jared Winoker:

For your reference, this is an overview of today's CME program that you can go back and look at at your discretion, and here's a quick overview also of the agenda that our speakers will be going into today. So with regards to CME, you can go ahead and receive a survey from Michelle Paoli via email. What you want to go ahead and do is indicate which seminars you've attended during the previous calendar month, and then you'll have your CME certificate emailed to you. Please, do make sure you fill out the evaluation questionnaires at the end of this in each seminar as these are important for securing your CME credits.

Dr. Jared Winoker:

I do want to remind everyone that there is a Q&A function on your interface in front of you. We encourage you to participate as our speakers will have an opportunity to answer your questions directly. Don't use the chat function, and of course, remember that all this is being recorded. So if there's anything you've missed, please do check back with our website to view this later date. So without further ado, I'll turn it over to Dr. Polascik.

Dr. Tom Polascik:

I'd like to welcome everybody. As a introduction, the Focal Therapy Society was founded in 2019, and we're currently partnered with the Endourological Society. So we hope to bring you a lot of content in the next year regarding surveillance for prostate cancer detection, different types of imaging modalities, and minimally invasive treatments using focal therapy. I'd like to introduce our first speaker Dr. Art Rastinehad. He's currently the vice chair of urology at Lenox Hospital, and he's the Northwell Health Systems director for prostate cancer therapies. He has a vast experience, not only on the image targeted treatment side, but also serves as a radiologist and interventional radiology. Dr. Rastinehad.

Dr. Ardeshir Rastinehad:

Thank you, Tom, for the introduction. I like to thank the Endourology Society for a course supporting the Focal Therapy Society, and it's my pleasure to be here today. The cornerstone of any good program. I'm going to try to go over the nuts and bolts to help everyone today. The secret sauce. Everyone wants to know how we do it, and I'm going to tell you what the secret sauce is. There is none. It's just a lot of hard work and getting a great team to work with.

Dr. Ardeshir Rastinehad:

Speaking of the teams, you really have to look at these components. Radiology is your primary area focused because this is where the patients are going to become through. It really matters on what imaging is being obtained and how the quality of that imaging will impact your patient care. It's having your colleagues and partners convert over to an MRI-based screening program and then choosing the modality for therapy. There's several choices out there. I'm not really getting into that today. I'm talking about the foundations and the nuts and bolts of the program and having a focal therapy working group. You need to have a closed loop system for feedback so you can learn from your mistakes and learn from your successes on how to optimize your program.

Dr. Ardeshir Rastinehad:

We've been saying this for years, but it is really garbage in gets garbage out. Unfortunately, as I really try to highlight, imaging plays such a major role. If you're not involved with the imaging for your patients, you're going to have a difficult time selecting patients for focal therapy, because if you have a poor quality MRI that underestimates or does even visualize tumors, you may be treating a tumor missing one in another area, and this does happen, and we really try to minimize this by having the strength of our team and our pathway as well as the quality of our imaging.

Dr. Ardeshir Rastinehad:

As things have changed over time, we've gone digital, the full digital. Digital biopsies are now the fusion biopsies today. There should be no more blind biopsies. This should not be happening. The AUA in October last year endorsed image first before biopsy, which really lends itself to building a focal therapy team.

Dr. Ardeshir Rastinehad:

What are the old triggers for biopsy? We know what they are. An elevated PSA and a nodule on exam. But that does not exist, and it's no longer viable. You should be using risk calculators, imaging, and even biomarkers to select patients for biopsy. So we're shifting from a majority low-risk disease to intermediate and high-risk prostate cancers by using this pathway, and in that, we are detecting focal diseases that may be amenable to focal therapy.

Dr. Ardeshir Rastinehad:

A lot's changed over the years since these two great mentors of mine, Brad Wood and Peter Pinto. As you guys all know, we had our first focal therapy meeting in 2008. Since then, the field has just exploded. The first ever publication was almost 20 years ago using imaging for biopsy, and I think we've come a long way, but we have a long way to go.

Dr. Ardeshir Rastinehad:

What is fusion? Well, every program is pretty much based on this is the idea of overlapping the sensitivity, specificity of a high quality MRI with the ease and use of ultrasound in your office or in the OR to perform the biopsies. This 3D data that we obtained, we can use later to select patients for focal therapy.

Dr. Ardeshir Rastinehad:

I want to make sure everyone understands how fusion works because every technology is the same at this point. It uses surface rendering. That means all those little triangles on top of a prostate dataset, which this could be an ultrasound or an MRI is key. So if you have a poor quality MRI or your poor segmentation on your ultrasound, you're changing these datasets, and it's very hard to align, get this good co-registration.

Dr. Ardeshir Rastinehad:

I'm going to dumb it down a little bit for just a graphic. If you look on the left side of the screen, you see two datasets, two squares that are not aligned, then on the right where they are aligned. Where you're using these small triangles and matching them because they're each unique to the surface rendering of both objects, taking this one step further, a common pitfall I see in patients or in places when I go and visit is, are they including all the prostate on the segmentation on the MRI? That's the entire prostate.

Dr. Ardeshir Rastinehad:

So commonly, you're going to see people only include the first part, this peripheral zone and the central gland or transition zone and leave out the anterior fibromuscular stroma I've shown in purple. You see that purple. That is key because on ultrasound, the interface between the edge of the prostate and the capsule and the fat is really what helps shape the image dataset for ultrasound. So if you imagine you left this out, every single time you do a procedure, this is not going to look like you're getting a good fit to your MRI model.

Dr. Ardeshir Rastinehad:

Elastic warping. Now, I've put this image in here. Look at the upper right screen. Watch what's happened. There's a snap, and you've just changed all that data. I wrote you really did see this. Look at the upper right again. Watch that purple and green line. The green line is the ultrasound. If the MRI gets squished into the ultrasound format that's been made, and that's the challenge here. I think it's important to understand that I rarely use elastic warping because it alters the dataset, and I want everyone to realize that because if you have an altered dataset one day, and then you do a treatment the next day, this could pose a challenge with focal therapy and targeting lesions.

Dr. Ardeshir Rastinehad:

Again, the imaging is key. Sorry for my font changes. I moved to my work computer because of the faster connection. But 3T imaging. Make sure you have the key sequences and the dedicated team I talked about. But guess what? Even if you don't know anything, if you just get your department or your imaging center use the PI-RADS recommendations, that'll help elevate you to a quality MRI most places aren't even doing today. That's a challenge we're dealing with every single day, especially with outside films.

Dr. Ardeshir Rastinehad:

Now, I put this up here just as an opportunity for all you out there to take a look, and you don't have to be able to read an MRI. But these key facts will help you understand what good quality MRI can be. These are all T2 images on the left side of your screen, one, two, and three, and then the one in the middle. You don't have to have images like the one in the middle. That T2 image is the best I've ever seen. That's why I put it in a talk. But it's a person that's never had good wine wouldn't recognize it if you only drink bad wine. So at least now, you know what a excellent picture could look like and compare that for your studies in the future.

Dr. Ardeshir Rastinehad:

You should at least have some delineation between the peripheral zone and the essential gland in your imaging. You should be able to see that and some internal architecture. If you're missing this, and it looks like this washed out image B, you know you have a problem. That's not going to be really helpful for focal therapy.

Dr. Ardeshir Rastinehad:

The cool thing with these technologies, you can take data from your fusion biopsy and create 3D models for treatment. You can see the 3D model on the lower right-hand side screen. It's moving around right now. The blue is the urethra. The green is a targeted ablation zone, and you can plan for these things. That's what is so exciting about moving forward focal today. An example in the upper right is another picture when we look at, "What's the data available? How are we approaching this?" This is just an example of a biopsy or a treatment screen.

Dr. Ardeshir Rastinehad:

Again, when you're treatment-planning, it's nice to have these 3D pictures because when you do the procedure, you can see if the bone is going to be in the way, because the pubic bone can limit you. So it's important when you set up your case, you understand how you can check yourself and help, and that'll really give you that opportunity to avoid the pitfalls and not be able to get the needle in where you want it to go.

Dr. Ardeshir Rastinehad:

This is an example of a fusion screen of the information from a fusion biopsy is then used in plan to plan a cryoablation using 3D rendered ultrasound or ultrasound and 3D MRI data. The blue box on the top middle screen is the external urinary sphincter that I marked to hopefully avoid any damage to it during the treatment. You can see the ice ball around the target as well as a margin. This is really important stuff, and this is what's available today for all of you users out there.

Dr. Ardeshir Rastinehad:

To reinforce the idea, it's so important the pathway. You're involved in every step of the pathway. This is a study that looked at the difference of two approaches, same radiologists, same magnets, and a fusion biopsy. But the doctor that did the fusion biopsy, one of them reviewed the MRI before the case and segmented themselves, and that worked out to a 238% increase in the detection of clinically significant prostate cancer when you control for all the other variables, PSA, gland size, target volume.

Dr. Ardeshir Rastinehad:

So it's important to understand that you can have a real impact on your pathway. If anyone offered you a 238% return a stock investment, I bet you would take it. So I'm trying to reinforce these ideas that this does equate to some bottom line and building a program as well as your revenue streams because if you were missing these opportunities to find patients, you're not going to be able to build a program.

Dr. Ardeshir Rastinehad:

I like to, again, reiterate there's no secret ingredients. What do we use with our MRI in our programs? The image review is key. You have to understand the basics quality so you can speak to your radiologist. Again, I told you, use the PI-RADS documentation. The PI-RADS system was built... I'm not a huge fan. Everyone knows me that I get upset by what's in there, but it was the whole point of that document, was to lift everyone to a basic level that we can grow from. It's a minimum standard, not a maximum standard. So I want you to understand that, but that's how it gives you a conversation tool with your radiologist, at least get the best scan out of your systems by having this conversation.

Dr. Ardeshir Rastinehad:

If they say, "I don't really want to do it. It's going to take too long." You're like, "Well, the ACR says we should be doing this." So that really helps you. Number two, post-fusion biopsy review. Every case when I get done, I call the patients. I review the MRI. This gives me an opportunity to see what went wrong, what went right, was there discording path, and are they a candidate for focal therapy?

Dr. Ardeshir Rastinehad:

Also, I do a transperineal biopsies in majority of them. It's a dry run. It gives you an opportunity to... If this case was a focal case, are they away from critical structures? I showed you how to see the external sphincter, and I marked it on the MRI, and that can help you learn where it is so you don't damage it. So transperineal biopsy approach is a great opportunity for a dry run. I do it with a stepper and a grid. I know there are people do single point.

Dr. Ardeshir Rastinehad:

I think the thing I would like to say those people that do single puncture on the side, there's a certain amount of warping, and you deform the prostate. So you're not actually in the same exact area because you're pushing the prostate down or up to lineup the needle coming in. So it's difficult to have an accurate assessment of where those needles went on any of the fusion biopsy platforms, because you're batting the prostate around to try to get to a specific area.

Dr. Ardeshir Rastinehad:

The treatment planning. I really went over this. I talked about being involved in this. It's important for you and your radiologist to have a working arrangement. You need to have that support. Because unfortunately, if you don't have the experience of reading the MRI yourself, you're going to depend on someone else, and you should not get to the point where you're just treating a cartoon. Whether you come to the fusion biopsy or the ablation using this fusion software, you need to understand what went into it to get to that point. I think it's super important, and it's helped me a lot over the years teaching myself and learning from my mistakes.

Dr. Ardeshir Rastinehad:

Treatment follow-up. We all talk about this. It's really important that post-ablation imaging occurs. You have a follow-up biopsy schedule with tissue confirmation. If you're doing a lot of focal therapy and you're interested, the Focal Therapy Society actually has a registry that we're going to be tracking cases going forward, and we're getting a lot of collaborators, and this is something you could be interested in. You could always reach out and contact us, and we have a group that is setting this up. It's actually one of the speakers today. Dr. Tom Polascik is kind of the president or he is the president of the society, but Dr. Arvin George has been leading the push for the database integration. Tom [inaudible 00:15:29] and Arvin are really doing a great job pushing us forward.

Dr. Ardeshir Rastinehad:

So that's really the end of my talk right here. But again, I just wanted to reiterate these key facts for you, and this is doable, and I wish you guys all the best. I want to say thank you for everyone to allowing me to speak today. It's my pleasure to share these talks, and I wish you all the best. Thank you.

Dr. Tom Polascik:

So how many have done a cryoablation procedure in the office? The vast majority say, no, this is a very new concept. We will hear from Dr. Bianco shortly of how he went about doing this. I think that in the future, some of these treatments need to translate to the office space. Number two, regarding starting a focal therapy program. It looks like the answer was, I have an interest, but have not yet started. Hopefully, this talk we'll get some of you started. We do have proctoring available, and we have a number of courses on how to read an MRI and do both fusion biopsy as well as targeting for treatment.

Dr. Tom Polascik:

Number three, regarding resources at my center to perform focal therapy. The two most common answers is I have a solid foundation regarding a fusion biopsy in place, which is excellent. You need it, as you heard from Dr. Rastinehad. And second, my patients are beginning to request focal therapy. We're only going to see this increase in the future. I'd like to introduce our next speaker, Dr. Dr. Arvin George. He's a friend of mine. As mentioned, he's now the chair of our newly launched Focal Therapy Society registry. I would welcome everyone to participate because we need this data going forward. Arvin is the head of focal therapy at the University of Michigan. Dr. George.

Dr. Arvin George:

Great. Thank you so much, and I'd like to thank Dr. Polascik and Dr. Rastinehad of the Focal Therapy Society for giving me the opportunity to speak and also to the Endourological Society, and specifically Michelle Paoli for helping organize the masterclass series and integrating some of the concepts of focal therapy into that program.

Dr. Arvin George:

So I've been tasked with sharing the first steps in terms of selecting a treatment modality when you're considering starting a program. It looks like there's almost 40% of us out there at least within this webinar that are interested in starting a program and that have patients who are now asking about it.

Dr. Arvin George:

So what I'm going to talk about today, what are the key treatment considerations? What are the things that we were looking for in a technology when we're selecting offers to first ablated modality. I'll go briefly over the existing treatment modalities that are out there, both that are commercially available and that are also in process of development and then briefly with the patient selection by modality.

Dr. Arvin George:

So what are the things that we look for in a technology? What are the principles that we want to or what are the features of a technology that would be most useful, especially when starting out? So one is going to be patient selection and versatility. So if you look at this screen here with the images on the top of it, you can see there's a lesion in the midline closer to the apex. Then the bottom, you can see the right arrow pointing to a lateral lesion at the apex and then the membranous urethra. You can see the urethral sphincter lateral to that point to the green arrow.

Dr. Arvin George:

So there are some technologies that would be able to tackle both. Some will be optimal for one versus the other. So for example, for cryoablation, your ice ball would likely have to freeze pretty close to the sphincter, and it would not necessarily be the best treatment choice for this patient. So the ability for your technology that you choose to be able to treat different patients with different tumor locations and different tumor characteristics is important.

Dr. Arvin George:

The next item I think is the learning curve for learning the technology. Suddenly, the one initial concept is image-guided therapy in general and fusion, and that already is oftentimes a new skillset, though it's becoming standard of care for many providers. But this adds an additional layer on top of it, and every technology has its own nuances. So something, especially when you're starting out that is a short learning curve would be important, suddenly cost, whether or not it is approved and you can get reimbursement for it is going to be important to ensure that there's financial viability.

Dr. Arvin George:

Then also efficiency in terms of integrating it into your practice or workflow and also procedure length I think is something that most of us consider as an important feature, given that we have busy schedules. I know that Dr. Bianca will be giving a great talk in office cryo a little bit later.

Dr. Arvin George:

So what are the existing kind of commercially available technologies that have some sort of approval? So if you look at the ones in red, the ones in red are cryotherapy, HIFU, and radiotherapy. These have either a oncologic indication or a prostate specific oncologic indication. So HIFU has a new, even though the FDA approval is for prostate tissue ablation, the new CPT code that goes live in January of 2021, it specifies essentially an oncologic indication.

Dr. Arvin George:

Irreversible electroporation, laser, transurethral HIFU. These are all either prostate or soft tissue ablation, including microwave. So what are the new modalities that exist out there? I'm naming a few of them that are... This is about an all-encompassing list, but just to bring it to the attention of our participants, we have a gold nanoparticle for the thermal ablation and the nanotherm device, which is injectable nanoparticles followed by a stimulation of these within a sort of an [inaudible 00:21:35].

Dr. Arvin George:

There is bipolar radiofrequency ablation, Reviv, which is akin to the water vapor ablation, similar to resume for BPH. Topsalysin, which is an injectable agent, photodynamic therapy, and even boiling and non-boiling histotripsy.

Dr. Arvin George:

So how do you learn about all these technologies? Some of you who participated in the recent focal meeting know about this. But if you're interested in understanding what are these different technologies, you can go here, and you have different representatives from each technology, giving a short presentation on their specific technology. So you can learn about all of them within an hour, essentially.

Dr. Arvin George:

So this is also just a general schematic in terms of, how do you decide how to treat them. This is not exhaustive. This is just to frame it a little bit so that you can understand that different technologies have different strengths and different limitations. So for example, in the anterior gland, cryo is extremely safe. You can't necessarily orchestrate the exact shape of the ice ball. But actually, there's very little things that you can damage, especially in a primary case.

Dr. Arvin George:

For large glands and anterior lesions, sometimes the beam will not be able to reach if you're using HIFU. Posteriorly, you're getting close to the rectum. Cryo can be used. All other technologies can also be used. But it gives you a little bit of pause because you are close to the rectum, and it's kind of for people who have more experience would be more comfortable treating closer to vital organs. HIFU gives you the opportunity to create very specific and small customizable ablation zones with a high degree of precision at the prostate capsule. The apex is a challenge for all different focal therapy treatments. Certainly, with the dosimetry being a science, radiation therapy would potentially have a role at the apical tumors.

Dr. Arvin George:

Now, the bottom line is that there's... The point I'm trying to get across is that there's no one size fits all, especially if you're an early user. So either you pick a single technology and work within that technology's limitations and to the appropriate candidate and then eventually layer in additional technologies as you gain more experience to expand the patient population that you can offer ablation to.

Dr. Arvin George:

So why didn't I include cancer control as one of the main considerations. That's because there's really no difference in the ability of a technology to ablate tissue. We know that if you apply laser to tissue, it's going to destroy the tissue as long as it achieves the right temperature, similar with HIFU, similar with cryotherapy, and we know that these technologies can destroy tissue. That's not the question. Really, there has not been a single technology that has taken pole position with regards to having a significant benefit with regards to oncologic outcome. Every single technology have unique mechanisms of failure, and oftentimes it's due to patient selection rather than the technology itself. As long as you work within the practice of that technology, it should be entirely adequate to give a good oncologic treatment.

Dr. Arvin George:

Now, what do I mean by unique mechanisms of failure? So to give you an example, if you are treating a tumor that's close to the urethra, cryotherapy, which uses a warming catheter, well, you'll end up having a heat sink. But the temperature may not get cold enough to deliver a lethal temperature to the tumor. If you think about HIFU, as you create small little ablations zones, the gland can expand, and you could theoretically develop skip lesions or untreated areas between the ablation, but between the small focal ablation volumes.

Dr. Arvin George:

So in terms of versatility and patient selection, these are one of the criteria I mentioned early on. There are different technologies that would be especially useful in primary versus salvage. So for example, if they have an indication, such as HIFU does in salvage currently, if you look at gland size, so sometimes the gland size can limit the use of a specific technology, the size of the lesion or the cancer volume.

Dr. Arvin George:

If your absolute ablation volume of the area of each treatment is small, then treating large volumes of cancer can be a challenge for a specific technology, and certainly lesion location, like I pointed out in the first slide with those pictures, there are some technologies which will be more amenable or better suited to specific tumor locations within the gland.

Dr. Arvin George:

So also, there's a learning curve to any new technology. What does that learning curve consists of when we're talking about focal ablations. One is the treatment planning, and in some specific technologies, it can be complex when you have small ablations zones and showing that there's overlap between your treatments, making sure that you have an adequate coverage of doctors, the true lesion, but also the margin that you plan into it. Sometimes that is not automated, and it has to be manually done, and it can be a challenge.

Dr. Arvin George:

Additionally, there are technical aspects of every single technology, so-called non-biology if you were referring to ultrasound. But just understanding those technical aspects can be a chore in the beginning of when you're learning a new technology. So the simpler technology is I think easier if you want to become facile, especially early on when identifying a technology. Then afterwards comes to steps of refinement. After you understand the broad con technical aspects of a technology, you start to realize what are the nuances of treatment, and suddenly those technologies that are simple allow you to get to that refinement stage much more quickly.

Dr. Arvin George:

So what is a key consideration is going to be to ensure that there is financial viability of the technology that you use. In terms of costs, there's a cost of acquisition, and that's either to you, your hospital, your practice, and then there's a cost to the patient, and that makes a difference. If the cost to the patient is high, you're going to decrease the number of patients who are going to be illegible for a specific technology or treatment.

Dr. Arvin George:

If we look at FDA approval and reimbursement is often tied quite closely together, but it actually lets you know whether or not, one, it's financially viable, or second, if you even have access to that technology. The FDA has granted approval usually for a soft tissue ablation or prostate tissue ablation for most ablative technologies rather than reserving the prostate cancer ablation for most technologies. Cryotherapy was historically grandfathered in, and that is why it is approved by the FDA, and it is also included in guidelines. If it is not specifically approved by the FDA, sometimes these technologies meet the guidelines by the role of larger bodies of evidence that support its use, such as the use of HIFU in the salvage setting.

Dr. Arvin George:

Then there is reimbursement. So there are some technologies that are covered by insurance and then some that are not, and they would be considered a non-covered benefit. What that means is that if you're going to offer a technology that is a non-covered benefit, that means that that is going to be an out-of-pocket cost for the patient. I know that there are people who are joining us from multiple different countries today, and oftentimes a non-covered benefit may be applicable to you as well. I don't think this is specific to the to the US market or population.

Dr. Arvin George:

So when we think of acquisition costs, what do those entail? How do you even know, what is it going to cost you to get started with a new technology? There are usually three different models. You can purchase it outright. You can lease it. Then you can do a per-click model. So purchase obviously will have the highest out-of-pocket capital cost to start with. But once you establish a high volume, your overall cost is low. With a lease, it's kind of a middle-of-the-road cost. But you don't have to have a large amount of capital upfront. Then there's the per-click model. You are going to pay more per case. However, you take on less risk, because if you don't have the patients, if you don't have the volume, then you're not paying for the technology.

Dr. Arvin George:

So when I started off and even continually to this day, I personally use a per-click model that allows me to adapt to the market and the environment. We do accept a higher cost and a lower margin for this reason starting out.

Dr. Arvin George:

So I mentioned that the efficiency of the procedure and the procedure length. One of the things is the consideration of what type of anesthesia is required, whether or not there's paralysis, whether it's sedation or if you can even do it under local anesthesia in the office. But like we'll hear about later, the ablation volume of each technology, so here you can see an example of isotherms for different cryotherapy needles. If you can form a large ablation volume in a single treatment, that improves the efficiency of your procedure and reduces your treatment time. Ideally, in my opinion, you want that procedure time to be really two hours or less. Otherwise, it can become tedious and challenging to be able to maintain a high volume.

Dr. Arvin George:

Then finally is access. At the end of the day, you need to have an efficient way to access these new technologies, whether that means that you're able to get to a third party vendor to be able to use it or lease the device or use it per-click. There are some new technologies that are in the space that, for example, urologists may not always have access to treatments that are performed in [inaudible 00:31:41] and that can be a little bit of a challenge. So you have to partner with a radiology or a hospital to integrate it, even though these technologies are great, that they can be barriers to access to a new technology.

Dr. Arvin George:

Now, when you're starting a new focal therapy practice, what do I think are the key tenants that you want to adhere to? I would say starting it out in an ASC or a hospital because that limits your personal exposure or costs, and they can build at a high level. So they can absorb a higher cost of procedure than you can in your own practice initially, to start out. You want to contain your cost to ensure viability. Even in the beginning, it's easy to spend big just to make things easier. But you have to be considered of this because if this is going to be a long-term thing for your practice, then you want to make sure that you contain your cost beyond. I would recommend a per-click model to start, and I'm choosing the single technology. The most accessible, I would say, currently are going to be cryo or high HIFU, or you can use both if you have access to it. But if you're going to choose a single one, make sure that you work just within the limitations of that technology for patient selection.

Dr. Arvin George:

Then finally, if you're looking for a patient population to start with, I think salvage candidates are going to be your lowest barrier. They oftentimes have limited treatment options with significant added morbidity or radical treatment options, and also, you have a patient population who has a localized recurrence, usually or oftentimes to a single lobe of the prostate or a single location, and you don't have to worry about the other side because it actually has already received a treatment if you're considering a patient who has biochemical recurrence after radiation.

Dr. Arvin George:

So they are an easy patient population to be able to offer this to. So I'd like to thank you again, and we'll be welcoming questions at the end, and I'll turn it over back to Dr. Polascik.

Dr. Tom Polascik:

Thank you, Dr. George. Excellent presentation. I'd like to introduce our final speaker, Dr. Dr. Fernando Bianco. This gentleman is a thought leader and is really the first one to think out of the box and figured out how you can do cryotherapy in an office setting. He has a vast experience, and I think a lot of us feel that patients at some point are going to want to come to the office and be treated, and we need to figure out how to do these things in a more outpatient center, Dr. Bianco, looking forward to your talk.

Dr. Fernando Bianco:

Thank you, Tom. Thank you to Art and Arvin. Excellent talks, and really thank you very much for your kind words, Tom, and privileged to be presenting this data and doing this presentation for the Focal Therapy Society. Those are my conflicts of interest, and without further ado, we'll continue with the talk. So where were we at the arrival of the millennium? I think Art addressed this in the earlier talk is that focal therapy was just an inception. Like you said, the first meeting was in 2008.

Dr. Fernando Bianco:

So back then, we were really looking at, by the time I was a resident and then a fellow at the work that's being done in Scandinavian Prostate Cancer Group, the PIVOT trial were on the works. But we're really dependent on level 3 serious. Prostatectomy was for osteologists the way to go, most of them. To put it in an analogy is stealing this life from my good friend, Andrew Stevenson, open prostatectomy was like the market leader. In this curve from Clayton Christensen, the innovation dilemma, basically open prostatectomy was the blockbuster in town. We were detecting more tumors, doing more surgeries, techniques were being perfected. Literally, innovations were happening then.

Dr. Fernando Bianco:

However, the real deal was the laparoscopic and eventual robotic movement that was starting, that was confronted with skepticism, yet it was initially done as more and more people started looking at. So what happens 20 years later? So we have now level 3 information from three randomized studies. So what was the message? The message from the Scandinavian Prostate Cancer Group, which was 81% of patients have palpable disease. So clearly not the ones we were detecting nowadays. There were no survival differences.

Dr. Fernando Bianco:

The early cancer specific survival differences were absurd, instead of getting wider, got shrinker over time. The mean benefit over a 23-year period was about 2.9 years of life. If we go to the PIVOT trial with the most recent publication this year, 70% of death events, we could see that the surgery provided just a year average of gaining in quantity of life. However, it imposed a three times greater risk of incontinence and twice at least, and erectile dysfunction started with a group that already had a high prevalence of erectile dysfunction.

Dr. Fernando Bianco:

When we look at the ProtecT trial again that [inaudible 00:36:42] with radiation, we see that there was no benefit so far in early findings in survival. But indeed there was the active monitoring group. About 40% of them basically were converted into surgery and radiation. That's a critical end point because when we look at focal therapy, the conversion rate will be certainly one of the outcomes that we want to look. So basically, in the 2020s or late 2010s, this decade that's finishing really radical prostatectomy for urology, this has become the Netflix, depending on if you have, and most of them are done robotics. I've done thousands of them. However, we know that it doesn't produce the results that we expected.

Dr. Fernando Bianco:

There are clear indications for it nowadays. You have 55 with a PSA between 10 and 20. Probably, that's the call, or if you're younger than 55 or at least in grade two or worse, then you should probably do that. On the other hand, if you're older than 60, and at least in grade one, you probably should not be doing that. You should consider surveillance or focal therapy.

Dr. Fernando Bianco:

So in the current paradigm, it's a dichotomy. You either go black and white and either you do whole gland treatment or [inaudible 00:37:54] treatment. I will contend that the reason why surveillance was done is because we couldn't find those tumors. We couldn't see those tumors, and basically, we went ahead, and to avoid harm, you basically observe this patient. By doing so you aim to preserve continent, erection, ejaculation, in other words, having better quality of life. Now we know that with radical treatment, the gain in life expectancy is not as much as we know, and the loss in quality of life is worse than we expected.

Dr. Fernando Bianco:

So what's the case for partial gland ablation. I think that Art and Arvin put it well together. So to just say it simply, now with fusion on the hands is about preserving quality of life without burning any bridges. That's usually what I tell my patients. Why did we choose to go with cryo? Well, basically, the story is long, but in 2012, after [inaudible 00:38:47] came out, we were stunned with the results, and we started thinking a little bit different on how we could help patients and MRI fusion devices were coming. As we started doing this and we moved into the office, we were able to develop this several steps that were discussed well by Art and Arvin today.

Dr. Fernando Bianco:

One of the reasons that we chose cryo is because it was indeed the label by the FDA for treatment of prostate cancer. The reason why it was labeled is because it was a [inaudible 00:39:18]. Dr. Polasciks is an ample contributor to the old registry, where about a third of patients were treated focally. Now, it's not what we're doing now because we're adding the whole layer of fusion that adds further safety, but there was a premise, and there was data there that could show that this was effective and safe.

Dr. Fernando Bianco:

So that's under local anesthesia [inaudible 00:39:43]. So what are the origins really of that? The origins were really some work done by a good friend, Winston Barzell back in 2002 thinking about how to treat the prostate focally and starting at a good diagnosis with the saturation biopsies and segmenting the prostate and thinking in this view. However, Winston basically refer that to do 50 samples on the local anesthesia was too much for patients to take.

Dr. Fernando Bianco:

When we look at the literature, really, there's a paper by Kubo published back in 2009, addressing biopsies that show on a dual work that it could be tolerable. But they were taking up to 26 samples. However, this had no traction. Another paper by Iremashvili published in the British Journal of Urology, 150 patients randomized to a pudendal versus a strict perineal block. Again, there was no traction afterwards. The problem here was with the pudendal block, they will have paraesthesia for a couple of days, patient you'd feel comfortable.

Dr. Fernando Bianco:

There's another big study by Pepe and Aragona with 3,000 patients on transplanting all biopsies. However, they went from local to spinal or general. So again, the whole thing didn't have any traction. As we work on this technique that we developed, we decided, because of good advice from other friends, to go into the US patent office and really patent a method and patent our vision of where we thought this was going to move if it was going to be successful.

Dr. Fernando Bianco:

Then one of the premises, well, of using MRIs, not just to looking at the area, but also looking at the probabilities that certain [inaudible 00:41:22] are going to have and of having cancer and then addressing treatment to those areas so we can model that and eventually be more successful and control better whether a patient has success or not in avoiding harm.

Dr. Fernando Bianco:

So as well covered by Art this morning, I mean, you can try to establish your own fusion program, but I call it super woman or superman phenomena, in which you acquire the imaging, you interpret the image, and you do the software processing, everything that are expressed very well. You determine the area to be treated. If you are in an academic setting, I think you got more likely to have success with this things. It requests a lot of teamwork and are distressed at in his lecture as well. Of course, it requires imaging. Art said garbage in garbage out. It's the same thing. If the image is not good, you're going nowhere.

Dr. Fernando Bianco:

The other model, however, which I think will be more easily to implement and much more inclusive to all urologists, not academics, but also the community will be an outsource model, where you outsource all this several steps, like the acquisition, the imaging, planning, the software processing, and you just focused on what you do, which is basically understanding better the MRI, but you focus on the procedure. Rather, it's a fusion biopsy and then a fusion treatment.

Dr. Fernando Bianco:

So you focus on the clinical principles and the data it acquires, and this is critical, so you can know your results as well. So we started the program back in 2014, and we have been able to train over 24 urologists since. So this has gained traction. One of our good friends, Dr. [inaudible 00:43:07] was able to implement our technique of local block in the Andrews Clinics in the Netherlands, and also we started this with our friend, Jim Hu at Cornell, and we have done it with several other of our colleagues that have come and seen what we do.

Dr. Fernando Bianco:

So the best way to understand what we're doing in our program is to start with a clinical case, a 64-year-old with a PSA around eight. He has adequate erections, and he has a hypertension, et cetera, an MRI disorder, and you see [inaudible 00:43:37] that basically is shown in the screen. He goes into our program, which we registered at theclinicaltrials.gov, and it's approved by organization IRB, in which we establish it with the aim of having events. So the eligibility is ample.

Dr. Fernando Bianco:

I will suggest that you going to start our focal therapy program nowadays. I will focus basically on what is in yellow lesion rate ones or two, and if they're 65 and older, threes, and then with less than 50% of the prostate [inaudible 00:44:08]. The other critical element is the follow-up. These are the patients that require the closest follow-up of all. Basically, you don't want anybody falling through the cracks because the price is too hard to pay.

Dr. Fernando Bianco:

So anyway, at three months, we get our first PSA. We get flow studies. Then we do the PA PSA often the first year, an MRI at a year is mandatory. Depending on the EMR, and I'll show you some data why we will consider a biopsy, MRI, and PSA dynamics. If that is negative, then we follow them every six months, and we will do MRI based on PSA dynamics or at fixed points, and then we'll do a biopsy if there's any abnormality on the MRI.

Dr. Fernando Bianco:

This is how it gets done. So the superficial block starts really close to the anal verge, and then we go really from lateral to medially, kind of like dissecting that triangle. We do that on the right and left side. Then we advance the transrectal probe. We like to use this [inaudible 00:45:05] in a grid because that stabilizes. The patient is in lithotomy, and you're not really rubbing around the pro, which is one of the things that causes more discomfort.

Dr. Fernando Bianco:

The grid allows us to be precise, to get into the place we want to be. Then we go with a periprosthetic block, like is being shown right here. We do it again on the right and left side respectively. After this, we'll be ready to do the fusion. This is the MR with the already plan. So we plan everything ahead of time as we outsource it. Then basically, we do the segmentation of the ultrasound image on the fusion platform, and that fusion platforms has on the background, the MR with the entire plan.

Dr. Fernando Bianco:

So after we have segmented the prostate, we start doing the card registration, and it uses a sort of a deformable co-registration based on algorithms, and it adjusted the prostate as you go laterally, of course. Then you are ready to go into the sagittal view, where you're going to actually do the procedure. Here you can see how we're taking the biopsy in this patient on certain areas. It seems to have a higher resolution for the apex anteriorly, and we just take samples from the suspicious areas, but we also take random samples.

Dr. Fernando Bianco:

All right. Here you can see the position. So we know exactly where they are. The coordinates on the right-hand side allow us to know where they were positive in this case, at lesion three plus four, and another core three plus three. This is the same patient now coming back about a month later for treatment. The block is essentially the same. We actually started doing the block on the cryoablations, and then we translated it to the biopsy. This procedure will be longer than a biopsy. It takes 20 minutes. The cryo takes us an average an hour. In here, you can see again the mesh of the AMR show in the treatment area that we want to target, that we picked up in the actual CryoProbes, and we're going to use.

Dr. Fernando Bianco:

So everything is already set up. So the urologist focuses on the treatment and how to get it done and supervise it in a safe way. That's the target area that we want to cover. We can see the outline of the prostate. It's saying fusion platform. As we can see here, there are basically three CryoProbes that we're going to put. So we're putting right now what we call a rod, a nice rod that creates a four-by-two lesion. In this patient, because the tumors at the apex, really, it's close to the sprinter. We put a terminal comfort. We do this based on the anatomy. I think that [inaudible 00:47:44] we can treat everything anterior, posterior, apical tumors. You can do it safely. We don't use [inaudible 00:47:50] and we don't need them. But we use when we need it, and the same goes with urethral warmers. Where we don't need it. We don't use it. That's roughly 90% of the time that we don't need it.

Dr. Fernando Bianco:

So anyway, we're advancing the CryoProbe, as you can see in the image, and once it's all said and done, we started the cryo process, and here's where fusion provides a lot of the advantages. The fact that we can see the outline of the prostate while it gets distorted because of the treatment based on the EMR provides us with the safety measures that we need. We can even see the Foley here that is not getting effected by the ice ball.

Dr. Fernando Bianco:

The patient though is going to be on a lithotomy position for close to 60 minutes. Right? So usually, we use nitrous. We offer them nitrous if they want so they can do this. Or sometimes you just fall asleep. Okay. In the beginning of the program, we use some value, but after we migrated to a mattress, that works better. But the local block itself tremendously, we asked them what kind of music they want to listen, and some of the texts common, really chat with the patient throughout the procedure.

Dr. Fernando Bianco:

For security reasons, we didn't want to put the face of the patient or anything like that. But that's basically the two procedures at once. So what have we learned about this? This is this patient, again, three months later. PSA dropped from about 7.9 to one is IPSs improved, from 19 to five. You can see the flow rates before the treatment and after the treatment. So one of the advantages also is that we have improvements in urinary function, and I will show you how they get quantified.

Dr. Fernando Bianco:

The erectile function was preserved. Right now, this technique that you saw, this procedure is being done in three cities across the United States. We have an experienced of 800 patients with 935 procedures. So many patients have been treated for a second time. When we look at our series, we have done from focal to hemi gland to whole gland or what we call MR fusion target cryoablation or Smart TX. That's 80% of our patients.

Dr. Fernando Bianco:

In the cohort, less than 81% had a PSA less than 10, and 77% are tumors that are non-palpable. As you can see, one of the advantage with cryo is you can treat multiple lesions. We've done that 40% of the time, and most of our patients [inaudible 00:50:14] grade ones and twos, but about 25% [inaudible 00:50:18] four plus three or worse.

Dr. Fernando Bianco:

This show the number of patients and the frequency and the columns and the pain that they described by procedures, and essentially, you could see there the average percentage between two and three and the minutes is cross to an hour. We did an analysis on side effects on 500 or 25 of this patients, and basically grade-one complications or adverse events in 5% of the patients, most common being some hematuria, ecchymosis, that kind of thing. Grade three, five patients, most of them, those are defined by requiring [inaudible 00:50:53] about a month after the treatment.

Dr. Tom Polascik:

Fernando, we have to wrap it up. We have a 30 seconds to wrap it, and then we have to... Okay.

Dr. Fernando Bianco:

So going the PSA response, 75% is the delta, and you can see here that the biopsy rates about 35% at a one-year positive biopsies. But most of them 80% are clinically significant. The conversion rates are very small in both cohorts. As we have looked into what predicts having a positive biopsy after cryoablation, all of this factors have not. However, the MR using the PI-RADS are those areas that were not treated is one of those things that can help us. So in general, the functional outcomes, there's no incontinence, not hematuria. 74% of patients have improvement in flow rates and transient ED.

Dr. Fernando Bianco:

So what do I tell patients? I tell them that I'm confident that tumors will be destroyed, that we're not burning any bridges, that quality of life will improve. I stress them to cancer may come back. So surveillance is critical. So I think that at the verge of this, manual focal therapy will be inclusive to all urologist, not exclusive, and it's the next disruptive innovation in our field. I want to thank you very much to all of the attendance, and especially Dr. Polascik for his invitation today.

Dr. Tom Polascik:

Thank you. I'd like to thank all the speakers. These were very informative talks. I'd like to thank, again, the Endourological Society. We've been working as a working group for the past 10 to 11 years, and the Endo Society has been very supportive of the idea of image targeted ablation from the very onset, and right now, we're working with them to bring these educational presentations to you. I'd also like to thank our sponsor, Varian, and hopefully we'll have more focal therapy topics during 2021.

Dr. Jared Winoker:

Fantastic. Thanks Dr. Polascik and everyone. That was really great. Just as a reminder for everyone, show continues next week. We have another webinar, where we're going to be diving into robotic retzius-sparing prostatectomy. Again, a reminder you see on the bottom, go ahead and visit the endourology.org website in order to register for that class.

Dr. Jared Winoker:

Again, you can also rewatch this webinar and all of our previous webinars there. For those who aren't members of the endourology society, I certainly encourage you to join. There's a host of benefits, including, but not limited to full text access to all the society journals. Again, for more details, go ahead and visit the society website. Finally, a not-too-early reminder to save the date for the World Congress of Endourology and Technology, which has been rescheduled for next September 2021, again in Hamburg, Germany. Thanks again for all joining. We'll see you next week.