Faculty: John Ward, Behfar Ehdaie & Massimo Valerio

Moderator: Tom Polascik & Eric Barret


John Ward, MD

John F. Ward, MD FACS is Professor of Surgery, Department of Urology, M. D. Anderson Cancer Center at the University of Texas, Houston.  Fellowship trained in Urologic Oncology at the Mayo Clinic, Rochester, MN., he returned to the U.S. Navy to complete a career serving his country before joining the clinical faculty at MD Anderson in 2006.  At M.D. Anderson, his clinical practice has become narrowly focused on patients with prostate and testicular neoplasms.  His clinical practice supports his research interests in prostate cancer imaging, biopsy and ablation technology with an emphasis on the expansion targeted prostate cancer therapies. He has authored multiple definitive manuscripts and book chapters that underpin the basis for prostate cancer focal therapy. 

 

Behfar Ehdaie, MD

Behfar Ehdaie is a urologic surgeon focused in prostate cancer treatment.   His research has focused on defining the utility of imaging in prostate cancer diagnosis and examining predictive models incorporating clinical and pathologic characteristics to better classify risk in men with localized prostate cancer. He leads the active surveillance program for men with low risk prostate cancer and investigates the impact of pathologic factors, serum biomarkers, hereditary DNA mutations, and multiparametric prostate MRI as predictors of disease progression.  Additionally, he is examining quality of life in men managed with active surveillance using validated instruments measuring sexual and urinary function, anxiety, and outcomes after focal therapy.  He was the principal investigator of a national multicenter trial examining the safety and efficacy of MR-targeted focused ultrasound to treat prostate cancer using focal ablation.  He is dedicated to improving patient autonomy and enrollment in surgical clinical trials and helped develop a novel method to randomize patients using a “two-stage” consent.  He has developed a standardized methods to communicate risk with prostate cancer patients on active surveillance and led a collaboration with Harvard Business School adapting negotiation theory in prostate cancer decision making.  Dr. Ehdaie is an international expert in prostate cancer, and have done numerous invited presentations to academic medical centers and professional societies  in the United States and around the world. In addition, he is a member of guideline committees that determine optimal prostate cancer management

 

Tom Polascik, MD

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.

 

Eric Barret, MD

Dr. Eric Barret is a urological surgeon at the Montsouris Institute in Paris, France. He is a recognized expert in minimally invasive techniques for the treatment of urological cancer, and particularly prostate cancer. In addition to extensive experience in robotic surgery, he is engaged in improving the management of localized prostate cancer, and for selected patients offers innovative, less invasive therapeutic approaches such as focal therapy.  He has been involved in a number of studies in this field, including evaluating the different energy sources for focal approach such as HIFU, cryotherapy, vascular targeted photodynamic therapy and irreversible electroporation.

In addition to these clinical activities, Dr. Barret is an active academic urologist and writer, with many international publications to his credit.  He chairs the Ablative Group of the EAU-Section of Uro Technology (ESUT) and he is involved in ongoing collaborations in urological oncology. 

 

Webinar Transcript

Dr. Tom Polascik:

Today's session will be very broad topic on what is focal therapy. As an introduction, we want to thank Wasatch Medical Specialties. They are the exclusive distributor for Galil prostate cryoablation products in the US. This is the agenda. As you can see, the purpose is to provide education for attendees. The target audience is for people engaged in the broad treatment of prostate conditions and prostate cancer. This is CME accredited.

Dr. Tom Polascik:

As one disclosure, some of the topics that you see, depending on where you reside and practice may not be standard of care, but may be ideas and treatments in development. You will receive a survey from Michelle Paoli. Please indicate which seminars you have attended, and you will get your CME certificate. Please complete the evaluation questionnaire at the end of each seminar. There will be a Q&A function.

Dr. Tom Polascik:

You can submit your questions. Some of those questions will be responded to in writing. What we'll try to do is save the questions for the last five to 10 minutes of the program and answer some of the more broader questions at that time. All upcoming webinars are listed on the Endourology website, as shown there.

Dr. Tom Polascik:

So today's session is What is Focal Therapy. I'd like to first introduce our moderator, Dr. Eric Barret. His photo is on the right. He is a urological surgeon at Montsouris in Paris. He's a recognized expert in minimally invasive technologies. He coined the term a la carte approach. He has extensive experience in robotics, HIFU, cryotherapy, and vascular targeted photodynamic therapy, along with irreversible electroporation.

Dr. Tom Polascik:

In addition to these clinical activities, he is the chair of the ablative group of the EAU Section of Uro-Technology and is on involved with ongoing collaborations with urological oncology. To introduce Dr. Barret, who will then run the program.

Dr. Eric Barret:

Hello, thank you, Tom. Thank you for this stunning introduction. Thank you for the invitation. So I'm very happy to share this session with you. The masterclass will be divided into four parts. We will have three very interesting talk of 15 minutes each and 15 minutes for discussion. So the talk will be given by three great experts, and they will cover three topics. First, the definition and the ablation template. The second is the status of the untreated prostate parenchyma after focal therapy. The third one is the quality of life in the patient with using the prompts after focal therapy.

Dr. Eric Barret:

So let me introduce the first speaker. The first speaker is Dr. John Ward. Dr. John Ward is a professor of surgery in the department of urology at the MD Anderson Cancer Center at University of Texas Houston. After fellowship in urologic oncology at the Mayo Clinic, Rochester, he returned to the US Navy to complete a career serving his country before joining the clinical faculty at the MD Anderson in 2006. He is a great expert in prostate cancer management and in focal therapy. He has multiple definitive management and [inaudible 00:03:47] that underpin the basis for prostate cancer focal therapy. John, it's yours.

Dr. John Ward:

Well, thank you very much for the nice introduction, and welcome to everybody who's joining us on this masterclass. I think just as when we went to medical school, we first had to learn how to talk the medical lingo, and that's important when you begin your focal therapy program. So we're going to go through some of the terminology and the templates we use in focal therapy. So focal therapy is really the individualized treatment that selectively ablates known disease and preserves existing functions with an overall objective of minimizing the lifetime morbidity without compromising the life expectancy, in other words, controlling the cancer without affecting any of the functionality.

Dr. John Ward:

The early results from trials and prospective studies have supported the use of focal therapy as a potential standard of care option. But none of the available guidelines now include focal therapy because we lack the truly needed randomized controlled trials or even high quality data to really get these into the guidelines.

Dr. John Ward:

So in order to get them into the guidelines, we have to have appropriate study of what we're doing with focal therapy, and there's very various degrees of what is considered focal therapy, and that's what we're going to try to go over here so that as each of you starts to do focal therapy and starts reporting on what you're doing with focal therapy, we can understand what partial gland ablation has occurred so we can compare apples to apples. Because there are various means of performing focal therapy, it has the potential to complicate the comparison of the patient data, and as well, there's multiple ablative technologies that can be used for focal therapy that I won't get into in this talk, but that also has the possibility of complicating our comparisons of groups.

Dr. John Ward:

So focal therapy definitions are important because we want to compare apples to apples. So we need to be using the same nomenclature, and that'll help support the development and dissemination of focal therapy and society such as the Focal Therapy Society and the Endourological Society are spearheading efforts to normalize the language that we use to discuss this emerging field and hopefully make it become part of the landscape for patients.

Dr. John Ward:

Back about 10 years ago, Steve Jones and I recognized that we had a Tower of Babel in the way that we talked about focal therapy. So we tried at that time to come up with definitions and terminology for focal therapy. About 10 years later, once we really got organized as a society, we got an international coalition of experts together to really look over what we were doing for partial gland ablation and come up with our terminology that we now use to describe focal therapy.

Dr. John Ward:

We'll go through each of these terms as we go through the talk. Importantly, when you start talking about focal therapy and the use of templates for focal therapy, we come back to how we diagnose patients with prostate cancer. A lot of prostate cancer and the biopsies that we perform depended on what you were going to do with the information that the biopsy provided. When all we had was whole gland treatments, it was just a matter of finding, A, a focus of cancer within the prostate. That was enough to provide some sort of justification for moving forward with the whole gland treatment.

Dr. John Ward:

But as we go into focal therapy, it's not just finding that a patient has prostate cancer, but it's finding where the prostate cancer is and what the confirmation and the configuration of the prostate cancer is that becomes important. That's a much bigger challenge, but that also comes into how we go about using our templates for focal therapy.

Dr. John Ward:

One of the other things you have to consider when you're doing focal therapy is what your understanding of the biology of prostate cancer is and whether or not you agree that all tumors have to be eradicated, all tumors that are within the prostate have to be eradicated in order to have good oncologic efficacy or if you can really buy into the index tumor theory, where only the most aggressive of tumors have to be ablated or treated and the remainder of the multifocality of prostate cancer is not used or is not treated.

Dr. John Ward:

So no matter how much you do a biopsy, and we're going to go through this real fast, no matter how many biopsies you do, whether it's a saturation biopsy, you have to remember that you're only sampling a very small portion of the prostate. You can go through, as we did here, to look at what percentage of the prostate you're actually examining when you do a 100-gram prostate, and you come down to a very small volume of the prostate. So again, the information that you get from a biopsy, you have to use carefully when deciding on your template for focal therapy.

Dr. John Ward:

Performing the biopsy is also hindered by such things as the moving target of the prostate, moving every time a patient breeze, the swelling and the capsule defamation, and even the deflection of the needle tip towards the target that you're trying to get. We also know that the person who is doing the biopsy can be an independent predictor of whether or not the biopsy is positive. In this study by Lawrentschuck, he found that there was between 0.67 and 0.89 odds ratio, depending on which of the four biopsy physicians was performing the biopsy sample itself.

Dr. John Ward:

So all of this has to come into play whenever you're considering what you're going to use for your focal therapy template, because inaccurate information can lead you to the wrong conclusions. So which treatment templates. So you have to choose a treatment template that is commensurate with the sensitivity and the specificity achieved with the biopsy, given all that I just discussed with the biopsy, the limitations of the biopsy.

Dr. John Ward:

You have to choose a template that achieves the oncologic goal that you believe that is important for the patient, and you have to choose a template that the precision of the energy can actually deliver. Some of the energy sources that are available for focal therapy actually have a very broad distribution versus a very narrow distribution. So all of these should be considered whenever you're looking at the templates.

Dr. John Ward:

The templates in detail. You have true targeted focal therapy, where you try to identify every tumor throughout the prostate, oftentimes through some form of saturation biopsy, and then try to be able to get back to each of those locations to provide a very precise, focused ablation of those tumors. As I say here, it requires precise and reproducible localization of the cancer, and so it's not just that you find every cancer, but that you also have to be able to get back to that spot once you come to your ablation energy.

Dr. John Ward:

It does maximally preserve the prostate tissue. But cancers, you have to remember are irregularly shaped. We like to draw this axial view of the prostate that you see on your screen here. But in actuality, the prostate tumors extend into your screen and back towards yourself and are oftentimes three dimensional in shape, and you have the question of safety margins. If you identify a tumor here through a biopsy, how much of a margin around it do you have to include in your ablative pattern and the precision of the energy. Something like cryoablation is going to have a much field effect than something like a laser ablation.

Dr. John Ward:

How you visualize the tumor during the ablation. Some of these tumors, you're able to pick up through biopsy, but you don't necessarily see them, and so you have to be able to have some way or consider at least what you're going to do to visualize the tumor area. You then move into quadrant or zonal ablations of the prostate. This includes a larger volume of normal tissue within an area that's identified to have the cancer. There's a greater safety margin, essentially. As you start talking about your quadrant ablations, you have to include whether it's an anterior or a posterior ablation, whether it's towards the base or the apex of the prostate, and whether it's on the right or the left side, because all of these might come into play in our understanding of your outcomes.

Dr. John Ward:

You get into hemiablations of the prostate then. This is a lateral hemiablation, which again, increases the volume of tissue that's destroyed and thus include some of the multifocality at least on one side that is associated with prostate cancer. When describing your focal therapy, again, you need to use modifiers like anterior or lateral and right or left. This would be an anterior hemiablation, in which again, there's an increased volume of tissue that is ablated. It covers both sides of the prostate and stays away from the neurovascular bundles. It accounts for a lot of multifocality that you can see up here, and again, you have to use modifiers, anterior or lateral, as I mentioned before.

Dr. John Ward:

Then you have the hockey-stick ablation, which is something that we first described. Whenever you have a dominant tumor over on one side that you can identify, we've actually found that oftentimes through the way that we used to do biopsies, you would have contra laterally missed tumors. So we included this hockey-stick pattern here. Again, modifiers are required, left, dominant, right dominant, and there's even a posterior hockey stick that has been described using HIFU.

Dr. John Ward:

This was how we came to that hockey-stick technique. I'm going to go through this, and then we just recently published our trial with 23 patients that underwent hockey-stick focal ablation. Of interest, we did have eight patients that did have a positive biopsy. All of these patients had three biopsies following the hockey-stick ablation. We had eight patients that were positive, all of which were out-of-field positive biopsies. Six of them were less than a millimeter of Gleason grade one, so what we would consider insignificant, while two had Gleason grade two, that we could... are great group two that we could move on to additional focal therapy. Then we had very good functional outcomes from that.

Dr. John Ward:

Then finally, there's subtotal ablation, which is the maximal partial gland ablation that could be considered focal therapy. It tries to maximally preserve the rectum nerve bundles on both of the prostate while accounting for the multifocality that you oftentimes see within prostate cancer. So in conclusion, focal therapy implies the partial gland ablation using any of a number of different treatment templates that we just went over there.

Dr. John Ward:

Template selection is based upon your reliability of the biopsy information, the understanding of the prostate cancer biology and the precision of the energy source that you use to affect your focal ablation. It's important to use these standard nomenclatures that I just introduced to you so that when you describe your results to the rest of the community, we can understand what has occurred and compare them to the outcomes from other trials. Thank you very much for your attention.

Dr. Eric Barret:

Thank you very much, John. So we are going to [inaudible 00:15:48]. So right now, let's move on to the next speaker, an expert on the patient selection with Massimo Valerio. Dr. Massimo Valerio is a staff urologist at the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, and he is associate researcher at the University of Lausanne. After finishing his residency in Lausanne and obtaining a certificate in advanced studies in clinical research from the University of Lausanne, he joined the University College London Group as research associate and achieved a PhD in this university in 2016. Massimo is a member of several society. He's a member of the EAU Academy, urologist of the [inaudible 00:16:40] of the ERAS, and he hacks as editorial board member and reviewer for many peer-reviewed journals. So Massimo, it's yours.

Dr. Massimo Valerio:

Thank you for your kind introduction. I didn't know that my bio will be all said. Thank you. So my talk will be about patient selection. I think the previous speaker already highlighted how the patient selection is really the key to success in focal therapy. So I think it's really itchy topic if you want to join the focal community or if you're interested in focal therapy.

Dr. Massimo Valerio:

So during my slides, I'll go on... This is an overview of what I'm going to talk. First of all, these are the characteristics you have to look for in ideal patient who is candidate for focal therapy. I think the first one, it's [inaudible 00:17:36] is a candidate for treatment, which means he needs treatment to patients, because one of the criticism in the beginning in the focal therapy [inaudible 00:17:47] was that focal therapies were tweeting a lot of men who will otherwise be in automatic surveillance, and say, maybe in the beginning was the case, but nowadays it's accepted that is not the case.

Dr. Massimo Valerio:

So the first thing is that the patient needs treatment. The other characteristics, it's about the disease and the patient, and I will go through this. First of all, I think there are some characteristics of the disease, but there are also some characteristics to the patient. If I write something in my focal therapy program is that sometimes disease was a minimal to focal therapy, but not the patient I will talking about this later on.

Dr. Massimo Valerio:

Who are the candidates for focal therapy when you see a patient come to your office. This is a report from the PROMIS study. The PROMIS study was a validating studying for MRI, in which consecutive men with a suspicion of prostate cancer based on PSA or on digital rectal examination had really state-of-the art assessment, because they got to the same time and multiparametric MRI. It was biopsy and the template mapping biopsy. We are talking about 600, 596 men who never had biopsy before who had around 70 biopsy per patient.

Dr. Massimo Valerio:

So obviously, it's not perfect. But I think apart from being a study about MRI is a study about prevalence. If you look at the results, you know how many men in your office are coming for a suspicion of cancer and how many you should find if you're good enough.

Dr. Massimo Valerio:

Why good enough? Because MRI was blinded to the urologist and say all men, irrespective by the MRI phenotype, they got the biopsy every five millimeters in their prostate. Once again, if someone had the volume on the prostate of 50 mils, he got 60 biopsy in all parts of the prostates, the perineum that is a kind of position which can be achieved only by taking out the prostate.

Dr. Massimo Valerio:

What did they find in the study? I'm not talking about the results of MRI. I'm talking about the results of the biopsy. So if you take consecutive biopsy naïve me and you do all of this, you have around one-third of patients, which are those in white, which have no cancer at all. So it should be discharge or follow-up according to the PSA. You have another third of patients who have a Gleason 6, I mean, an ISUP 1. So most of these men obviously shouldn't be in anti-surveillance.

Dr. Massimo Valerio:

The other third of young men, most of them will have Gleason 3+4, and another minority will have 4+3, and they're really, really minority of biopsy naïve men with a PSA less than 20 as well as for the study who will have a Gleason 8, 9, or 10. Now, who are the candidates for focal therapy? Once again, I think we should not over-treat, and we should not under-treat. So should not able to treat can be watched beginning and then will have who are likely to have multi-focal disease will need a multimodality. I think they should go for that.

Dr. Massimo Valerio:

This is suggested by the pathology study in radical prostatectomy specimens. We are looking for these patients maybe more for the 3+4 and some men with 4+3 which are well-characterized. Now, since long time, everyone agrees that in a prostate, there is a dominant lesion in which you have the highest volume, and yeah, it's great. Obviously, not in all cases, but in most cases. But the [inaudible 00:21:59] to focal therapy has always been that she didn't have a means to know which was yeah with cancer and which was yeah with no specific anticancer.

Dr. Massimo Valerio:

Obviously, as Prof. Ward said, if you have to treat one man with a radical treatment, you only need to know whether he has cancer or not and what kind of cancer. But if you want to do a precise ablation, you really have to know which area is the counsel and also the areas in which you have no cancer.

Dr. Massimo Valerio:

So when you select your man, I think you are required to have a biopsy and imaging program which is established from before. So the first thing is always to do an MRI before. MRI has some [inaudible 00:22:45] which allow focal therapy. The first one is that you can see with good accuracy significant disease in the prostate. The other one is that most of the time, you can overlook no significant disease. So in this case, for example, we can see very well that the MRI can see the left lesion here around the right region, and you cannot see this model focus of Gleason 6, which is probably insignificant.

Dr. Massimo Valerio:

Now, you can only see here is that the MRI tends to underestimate the volume. Again, as the previous speaker say cancer has not round the shaper as we would like to see them. They are like a spider. So you have to account that there is some kind of ramifications that you cannot see on your screen when you look in an MRI. So when you see your patients, you can see this man will be illegible, I mean, in my practice for focal therapy, then you have to choose what kind of biopsy you're going to do.

Dr. Massimo Valerio:

So this is a key decision because you need precise biopsy. So what is a precise biopsy obviously? I think there are two ways of looking at this. The first one is to do random biopsy plus MRI plus fusion biopsy, and the groups from landmarks were really experts in the technique. They show the results in consecutive men undergoing random plus fusion targeted biopsy in their center. If you look at this graph, you can see that those were the MRI-visible lesion. So around 400 patients.

Dr. Massimo Valerio:

Those will be allegeable for focal therapy, which was either targeted or quadrant or hemiablation were around one-third of the patient. In other words, if you see a patient in your clinic, and yes, in this [inaudible 00:24:42] and MRI, there is around one of three chances that he's eligible for a focal therapy option. Now, obviously the question is if the patient is illegible on random and fusion biopsy, what happens if you take out the prostate and look whether he was really eligible. So they did this, and they say that in this patient, so there were only 46 of the under 75. So the accuracy of this model was around 75%.

Dr. Massimo Valerio:

In other words, you were correct three out of four times. Why you were not correct. There were two reasons. The first one was the index lesion was much bigger, and it was crossing the midline, which means the patient was under treatment if you had physical therapy, because they will have [inaudible 00:25:28] or a quadrant or targeted ablation or because the Gleason was higher than suspected before.

Dr. Massimo Valerio:

There is one way to do even better, which means to do the same they didn't promise. So to do a template biopsy of the prostate, do a number of biopsy. Then you get a lot of precision in the index lesion, which is the most aggressive one and also in the non-index lesion. So the groups from [inaudible 00:25:55] they found in this [inaudible 00:25:58] that if you combine both of them you have a detection of 96% for the index lesion and 92% of non-index lesion.

Dr. Massimo Valerio:

These are not only significant [inaudible 00:26:13] every lesion. Nothing is perfect, but is really close to be perfect to select your patients for focal therapy. The key feature I think for focal therapy is selection, in my practice is when you go through the MRI-visible lesion, when you goes through precise biopsy is the location of this lesion and the extension of the targeted ablation we are planning.

Dr. Massimo Valerio:

Obviously, you need to have a threshold of what you accept as untreated area, which is possible biopsy. This is something which is open debate. You can say based Gleason 6 one millimeters, three millimeters four, five non-visible lesion. There is no consensus about this. But we usually use three millimeters of Gleason 6 in a non-treated area is considered to be acceptable for focal therapy.

Dr. Massimo Valerio:

So this a few cases. So this one patient which you can see, he has a lesion in the peripheral part of the prostate. When we did the biopsy, we found only one lesion which was concordant. There was no biopsy possible on the other side. So this is I think perfect candidate because the location is very easy. It's in the middle part of the prostate. It's far from the neurovascular bundles. It's far from the sphincter.

Dr. Massimo Valerio:

There is no disease elsewhere. Patients access the focal therapy strategy, I think is the perfect case. These are the patients as a lesion, which is in young T or left side of the prostate, which you can see very well on T2 and the ADC maps. In this case, when we did the biopsy, we found also two millimeters of Gleason 6, which was on the other side. So I think also these patient is a perfect candidate, because again, the location of the lesions allows them to present a lot of tissue, and I think Gleason 6, two millimeters, you can observe with what we know today with a natural history of the disease.

Dr. Massimo Valerio:

This patient is a different one because he has a big anterior lesion, which is close to the urethra is crossing the midline, and you cannot see here because there is no coronal or [inaudible 00:28:32]. But this lesion was really, really close to sphincter. So I think this is where the worst candidate for focal therapy, for many different reasons. The first one, you cannot have margins of ablation because you will treat the sphincter. The second one, these patients are more prone to have a stenosis after treatment. The third one is that it's very difficult to control this onto your tumor, which really all around the prostate in anterior part.

Dr. Massimo Valerio:

This patient has a big lesion in posterior lateral side of the prostate. When we did the biopsy, we found bilateral, one side was visible. The other one was not visible. I think again, in this cases, with significant bilateral disease and once which is not reasonable, I think he's not a good candidate for focal therapy, at least as a standard option.

Dr. Massimo Valerio:

Now, you know you have to select your patient. You also have to select your energy. So the groups from Eric, they nicely showed this in this [inaudible 00:29:33] graph, in which you can see that depending on the location, we have different ablation modality, which is not the topic today. But basically, in the anterior part, you have needle-based technologies in the posterior part, I feel one of the best funds, and the apex is really difficult and in their experience [inaudible 00:29:50] brachytherapy could be a good option.

Dr. Massimo Valerio:

I think the parts [inaudible 00:29:59] process is the patient. You have a disease, and you have the patient. So you really have to counsel this patient because there are things that we know. There are things we do that we don't know. So if you want to look at what we use in the scientific community as eligibility criteria, I think the part trial which was done by the group from Oxford is a good example of increasing criteria for hemiablation, basically what I said till now.

Dr. Massimo Valerio:

So they randomized patients between radical prostatectomy and hemiablation. So we can talk to your patient is that, for sure, this is not subject to any kind of bias because this is a randomized controlled trial. There's nothing best. So if you do a focal or you do a radical prostatectomy, you can see the difference of 12 months. Urinary incontinence is almost not affected by focal because they are the same prompts before and after focal. Obviously, it's affected radical prostatectomy.

Dr. Massimo Valerio:

In the same level, erectile function, it's much more effective. So I always say to my patients, you need to know what you want, because for sure, you're not getting decked in the same. If you do radical prostatectomy or you do radiotherapy with other complications, you're not getting the same. So I think the functional value or the efficiency is really, really important. The third thing is that the patients should accept to the followup and the unknowns of focal therapy.

Dr. Massimo Valerio:

There are things we know as the preservation of erectile and continence after focal. There are things we don't know very well, which is the long-term outcomes of the five years. So patients are focal, they need close followup. When [inaudible 00:31:47] my patients who usually need focal, these are people they just didn't come to every follow-up, and I really don't know how they are doing till now after three or four years.

Dr. Massimo Valerio:

[inaudible 00:32:00] we know very well what happens in the first year. There are lots of reports in first, second, three years, five years, but five years is not enough in prostate cancer for the natural history, and we honestly don't know what happens after seven or eight or nine years. So this is not something to say that it will not be very good. It's something unknown, and the patient should commit to this.

Dr. Eric Barret:

Massimo, conclusion, perfect.

Dr. Massimo Valerio:

So in conclusion, I think focal therapy may be an option for many according to primary study. I think the patient selection is the key to success, and you really have to get imaging and biopsy right before embarking your therapy. I think you don't have to [inaudible 00:32:48] energy and for that the energy to every patient. But you should really have the right energy for the right patient for the right location and that [inaudible 00:32:56] to the patients and the surgeon should commit to the strategy and believe in it. Thank you.

Dr. Eric Barret:

Thank you very much, Massimo. So we're a few times to discuss at the end. Let's move now to the next to our last talk, entitled, why does focal therapy matter to the patient problems, by Dr. Behfar Ehdaie. Dr. Behfar Ehdaie is a urology surgeon at the Memorial Sloan Kettering Cancer Center in New York City focusing on prostate cancer. He leads the active surveillance program for men with low prostate cancer. Additionally, he is examining the quality of life in men managed with active surveillance and outcomes after focal therapy. He has developed a standardized method to communicate risks with prostate cancer patients on active surveillance and led the collaboration with Harvard Business School, that negotiation theory in prostate cancer decision-making. Dr. Behfar is an international expert in prostate cancer, and he's a member of guidelines committees that determine the optimal prostate cancer management. So Behfar, it's yours.

Dr. Behfar Ehdaie:

... very much. So it's a pleasure to be on this panel. Let's get through these slides. So my goal today is to... First of all, no disclosures for this talk, is really to discuss, why do we measure patient-reported outcomes and apply them in adaptive and focal therapy? So this was the International Consortium of Health Outcomes Measures. It's a great publication. That's a website on the bottom for everyone to review, and they have a specific one for prostate cancer.

Dr. Behfar Ehdaie:

But the goals are when we measure patient pouring outcome is to learn about how our patients are doing and subsequently use that information to improve performance. Our goal is ultimately achieve superior outcomes and with improvement, understanding our outcomes, that's how we can improve our outcomes. As the healthcare system continues to shift, what we accomplished shouldn't be based on how many things we do, but how well we do them, and that can only be measured by asking patients themselves.

Dr. Behfar Ehdaie:

So this was the landmark study that really launched patient report outcomes of prostate cancer. This was a comparative study of radiation therapy and prostatectomy. What's key here is that the median outcome of quality of life measures was used over a period of time from baseline to two years. Despite initial thoughts that patients with one modality do much better than the other. When these patients were followed out to two years, these outcomes became very similar.

Dr. Behfar Ehdaie:

It was a landmark finding which changed how we evaluate and counsel patients. So when it comes to quality of life measures and focal therapy, what surveys should we focus on? This was a collaboration that I had the privilege to be a part of, in which we outlined as a consensus, what the most important measures would be. So the conclusion was the Expanded Prostate Cancer Index Composite Survey, the International Prostate Symptom Score, the International Index of Erectile Function, the Male Sexual Health Questionnaire for Ejaculatory Dysfunction.

Dr. Behfar Ehdaie:

So I'll go through each of these quickly. So the EPIC 26, it measures urinary function, sexual function, bowel function, after treatment. This is a sample of some of those questions that patients would answer under the urinary function domain. The International Prostate Symptom Score measures urinary symptoms and bother. This would not be relevant post-prostatectomy, but it's very relevant in patients who continue to have a prostate after radiation therapy or focal therapy.

Dr. Behfar Ehdaie:

Again, the questionnaire is simple. It asks questions about obstructive and bothersome urinary symptoms with a final quality of life question. The IIEF measures sexual function across the domains of confidence, performance, satisfaction, and erectile function domains. This is a sample of those questions, again, focusing on those domains. The IIEF-6 specifically does include bother and symptoms that would be important when we talk about overall satisfaction with sexual intercourse.

Dr. Behfar Ehdaie:

So here's some key factors. One, the questionnaire begins by asking over the past four weeks. So we have to be understanding, especially initially after treatments, that these questions may not be relevant to patients who may have not engaged in intercourse due to the recovery of their treatments. The second, as was recommended by the International Consortium of Health Outcomes Measures, that the additional questions about the use of sexual medications or devices is recommended.

Dr. Behfar Ehdaie:

So as these studies continue and as we write studies in focal therapy, it's important to collect this information. As we talk about cutoffs for erectile function, the cutoff of a score of 26 or higher defines abstinence of erectile dysfunction. But what is the cutoff to find good erectile function? Firstly, terminology matters. So the choice is to use functional erection. This is defined by Dr. Mulhall in this publication, the Journal of Sexual Medicine.

Dr. Behfar Ehdaie:

Second, the cutoff of 24 was used as this represented a score using the domain of satisfaction that represented across all measures, a sensitivity specificity to indicate these patients. Although not above scores of 26, their satisfaction scores were considered good or above average. But is potency the only important sexual function domain for patients undergoing physical therapy? I would argue not. I think orgasm quality, ejaculation. In some men, there may be issues with chronic pain.

Dr. Behfar Ehdaie:

So the Male Sexual Health Questionnaire for Ejaculatory Dysfunction remains an important additional survey for us to ask our patients. This is a sample of that questionnaire. It's four questions not only asking about the quality, but also the bothersome affiliated to ejaculation.

Dr. Behfar Ehdaie:

To give you some insights, this was a study that we presented at the American Neurological association meeting of a pilot study and electroporation, where we did a longitudinal study of ejaculations assessment. What's very clear was when you look at quality of ejaculation across these measures from baseline to 12 months, there was a decrease in quality.

Dr. Behfar Ehdaie:

But more importantly, this was associated with bother. The bother peaked at three months post-treatment, and then we see a normalization, and again, a slight increase most likely associated with the timing of biopsies. But again, this is something that matters to patients both from the perspective of quality and symptomatic bother scores.

Dr. Behfar Ehdaie:

So patient preferences regarding sexual function and expectations after focal therapy should be identified and the discussion of outcomes must be expanded to sexual satisfaction. It's not just achieving an erection or question two that we often see cited in the literature. So I'll give you a little sample of what we're doing at our institution.

Dr. Behfar Ehdaie:

We have everything automated. This is our system, and I tell patients or physicians when they want to start their own program that they need to start collecting data. So first, defining outcomes most relevant to your clinical practice, and you have to achieve agreement among all faculty to collect data, and this must be done anonymously.

Dr. Behfar Ehdaie:

For example, post-prostatectomy, we've identified multiple things that we think would be important for us to collect and understand. Then there's no ideal outcome. But instead, the goal is to reduce variation among surgeons. I think this is an example from positive surgical margins after prostatectomy across multiple institutions, and we may not know what the right answer is because a patient with high-risk disease may not have the same positive surgical margin incidents as someone with low-risk disease. But the variation across disease types should be limited, which should be the goal of all patient-reported outcome measured assessments.

Dr. Behfar Ehdaie:

Then as this information is fed back to physicians, we should allow surgeons to adjust for clinical characteristics and provide feedback with real-time updates. For us, we collect information with emails and measures sent to patients every three months after their treatments. Then when this information is collected, adjusted in analysis and fed back to physicians, we are allowed to adjust within what we're looking for, whether we want to look at only in high-risk patients or whether we want to look at one-year data or three-year data. This has all been automated.

Dr. Behfar Ehdaie:

The lack of the communication of outcomes between patients and physicians leads to misperceptions of actual outcomes. This is important. What we sometimes hear from patients and what the patient's actually trying to communicate maybe different. We actually asked that question. So since starting the program here at Memorial, where we feedback outcomes to physicians, we found that feedback of outcomes improves the agreement of physician perception of outcomes of patient reported outcomes. So this is the correlation in urinary continence post-prostatectomy in patients. As you can see, the agreement percentage increase after the implementation of the Amplio program, which is a patient report outcome program in our institution.

Dr. Behfar Ehdaie:

Also, the patient outcomes help researchers understand trade-offs between decisions such as treatment versus active surveillance. This was a study in which we looked at the recovery of erectile function after surgery in a 55-year-old patient. As you would expect, there'll be a decrease in the IIEF-6 score and then increase in recovery over time. But the question always is, what if I delay surgery? Is there a benefit? Well, we can then mark and evaluate a patient at age 60 who underwent surgery, median outcome of thousands of patient report outcomes in those men in graph out, what that recovery would look like.

Dr. Behfar Ehdaie:

Then to assess between those five years of the patient gain, whether they underwent focal therapy or active surveillance, you can look at the baseline function of patients that you've collected over years to represent a true population base decrease in erectile function without treatment. We did that. When we looked at the area under the curve, it was very clear that delaying treatment in a 55-year-old by just five over a 10-year period improves the overall erectile function by two points, which is equivalent that was used in the trials for sildenafil and Viagra to look at for approval by the FDA for a aide for erectile function.

Dr. Behfar Ehdaie:

So a significant difference. So finally, when you look at... This was a recent study we published or we presented at the AUA when we did a systematic review of focal therapy studies from 2000 and 2019 looking at patient reported outcomes measured. The methods used to report data we'd found were very varied. So across thermal and non-thermal types focal therapy, it was clear that the outcomes we reported, whether it was different for surveys, whether it was different questions within the surveys, whether they were even collected or the time periods varied significantly.

Dr. Behfar Ehdaie:

These were studies that were collected based on the quality and methodology of number of patients, randomized control trials. So not every retrospective study was included. Even in those studies that we deemed as high quality, we noted this variation. So standardization does matter. I think the initial work to bring all those surveys together helped.

Dr. Behfar Ehdaie:

So in conclusion, measuring patient outcomes is vital, improve clinical care and manage patient expectations after treatment helps us learn the impact of novel focal therapy interventions on patient outcomes and improves patient care by reducing variation among physicians. It guides physician and patient decision-making. Finally, a key is standardizing methods to measure and report data is key for us to understand differences and improve across institutions. Thank you very much. Thank you very much.

Dr. Eric Barret:

Thank you very much, Behfar. Thank you all three for your wonderful talks. So we have seven minutes for discussion. So I have a question. My first question is for Prof. Ward. Prof. Ward, what do you recommend to a urologist who want to start focal therapy? We explained that there are different way of doing focal therapy. What is your ideal treatment option, quadrant, hemiablation, [inaudible 00:45:54] total ablation, for example, a patient with a one centimeter right side base posterior lesion, Gleason or ISUP 2? What do you recommend?

Dr. John Ward:

Well, I think what I was trying to point out in my talk is that you can apply different templates for your patient. As you coined, this is a very individualized treatment therapy. So it can become an a la carte, and there's no one template that is appropriate for all patients. What you have to consider, as I was trying to explain is what your goals of therapy are. When you look at Behfar's last talk at what your expectations for functional are, when you look at, as was described by Massimo in what your cancer outcomes are, your expectations on whether you're going to allow small volumes of low-grade tumors or not, that's going to define what you use as your template for that particular patient, even location of tumor.

Dr. John Ward:

One of the examples was a tumor towards the apex is going to have a much different template that you're going to consider or a targeted treatment that you're going to consider than one maybe towards the base and interior. So I don't think you can get locked into a single template for all patients, and it's good to know that all of these variations are out there so that you can personalize your therapy.

Dr. Eric Barret:

How do you find the lesion when you treat, because this is our main problem, how to find the lesion. So we have an MRI, we have a biopsy, we usually have a concordant disease. But how do you, I mean, in your experience, find a lesion during the treatment?

Dr. John Ward:

So in my experience, since we tend to do more of a template and are willing to sacrifice more normal tissue than others are, we will use the information that we get both from a targeted biopsy because most of the patients that we're considering for focal therapy do have some lesion that is visible on MRI, as well as the information that we get from the random biopsy.

Dr. John Ward:

So we'll include regions of the prostate if they have positive cancer, even if we don't see an area on the MRI. So we use a combination of both the targeted biopsy and the standard biopsy information. Now, we do use the Artemis device there's many different means of performing MRI, ultrasound, fusion-guided biopsy. We're also using the Artemis device to help us in placing the cryo-needles into the same location that we obtained the biopsy from. So there can be modifications for each individual patient to account for that.

Dr. Eric Barret:

Okay. Thank you. I have a question for Massimo. Massimo, how do you manage a patient with a lesion [inaudible 00:49:08]? I mean, in this patients selection, how do we manage this kind of patients due to systematic biopsy, and in case of a lesion, how do you offer to the patient?

Dr. Massimo Valerio:

I think obviously the radiologist is not really helpful because he or she doesn't know. So I think you need another measure to look at whether this patient is very likely to have a prostate cancer or not. So in my practice, we use the PSA density. So if you look at the study, if you have a very low PSA density, we don't biopsy these patients, and we follow them with PSA and another MRI, depending by PSA kinetics. If the PSA density is already done, in those cases, we biopsy them.

Dr. Eric Barret:

How do you biopsy the patient? So do you do the transferring out, transfer out? What is for focal therapy the ideal biopsy selection for patient? Transfer it out, transferring out. [crosstalk 00:50:17]-

Dr. Massimo Valerio:

I'm really committed to transperineal for different reasons. I mean, the first one, I think you don't have any anatomical issue, and you can biopsy the prostate wherever you want. I mean, the anterior part, the basal part, the apical part. I think you can even have a nice diagram of what you're doing afterwards. I can show here, but you have a nice model of the prostate. Again, in all the prostate, you're able to see a much less infection problems afterwards, and I think you don't have any problems with the mid constructable, which means the deflection of the needles, the problem with the fusion. I think the transperineal for me is much more immediate. So in our series now, we do 90% of our cases to be transperineal.

Dr. Eric Barret:

Okay. You say that the tumor is a spider? So we agree. So how do biopsy the spider? Do you do two, three target and biopsy around or just inside the lesion? Or how do you biopsy that? Because the problem is, as you say, or I don't know who say that, we have to find the right lesion for the right treatment for the right blah blah. So how do we target the lesion?

Dr. Massimo Valerio:

So I will reply to your question, but I'm going to respond. But the first thing to imagine is that obviously the biggest lesion, the less needles you need because you're not going to miss it. But the more of the lesion, the more needles you need to, because you can have fusion problem. So you can have problems in your targeting or deviation of the needles.

Dr. Massimo Valerio:

So in our practice, we did three or four lesions in almost three or four targets biopsy in the core of the lesions. We don't choose to do around the lesion, the extra biopsy. The reason for that, I think it's very, very difficult to reconstruct in three dimensional how far you were from the core of the lesion. I think if you're going to focal, you need to assume you have margins.

Dr. Massimo Valerio:

So in our practicing, we always take one centimeter, so margins. We assume that the spider is covered by our margin of tissue or normal tissue around the care on this. But what we do is that we always see the model from Basel, which means to biopsy all the prostate in all the areas. We accept the margins. What we don't accept are areas [inaudible 00:52:45] to the exclusion to be a focal therapy option for this patient.

Dr. Tom Polascik:

I have a question for Behfar. I remember I was talking to you and John Coleman about a year ago. I practice in Durham, and I think maybe some of the folks are more simple minded. But it became apparent to me that many of the city dwellers are really focused on things that urologist haven't considered, such as a ejaculation, ejaculatory volume, things like that.

Dr. Tom Polascik:

Traditionally, our outcomes have been continence, maybe how many pads can you get an erection with or without Viagra. So where do you think the field is going? We started really delving into ejaculatory satisfaction, quality, amount of ejaculation. At the same time, it's important to record these outcomes, but it's hard to have databases with really hundreds of variables. So what do you think is the future and the sweet spot for this.

Dr. Behfar Ehdaie:

Great question. I mean, two things to unpack there. One is, of course, survey fatigue is very important. So we have to be very careful how many questions we ask patients, and I think surveys are doing better and better jobs of being smart. So what we've implemented is if you, for example, answer, I'm not having erections, you're not going to answer six more questions about the quality of your erections. The survey stops right there. So smart and AI-driven questionnaires is key and also limiting the questions.

Dr. Behfar Ehdaie:

The second part of that is important. I think it matters what we're comparing it to, where patients began. I've become more and more aware that focal therapy represents the next step after active surveillance for many patients. So the comparative group remains probably active surveillance for many of these patients, and that's what they know, whether that's where they start or whether you're trying to decide between.

Dr. Behfar Ehdaie:

If we talk about delay in treatment, it's a delay from active surveillance to radical therapy. So when a patient sees themselves without treatment, then their quality of life represents multiple facets. So it could be quality of sexual intercourse. It could be pain. It could be not undergoing biopsies. So there's so many factors that I think will not be important when we compare really to non-treatment.

Dr. Behfar Ehdaie:

When you compare to radical treatment, of course, asking about is irrelevant because one group will not have semen or ejaculations. Perhaps orgasm scores will be important in that group. So I think the comparative group and in the direction I'm going mostly, as you can see, is asking questions that will be relevant for both patient care but also clinical trial assessment, for future ability to bring focal therapy into guidelines if feasible.

Dr. Eric Barret:

Behfar, I have a question. What about anxiety? We know that the patient who are diagnosed with prostate cancer are very anxious, and there are hallways. They have to face a great dilemma to be treated or not. Sometime when they choose focal therapy, we explain to them that this is, I would say, an investigational treatment. So maybe we had anxiety. So how do you [inaudible 00:56:05]? I know that for prostate cancer in your institution, you develop the MAX-PC questionnaire. What about focal therapy?

Dr. Behfar Ehdaie:

So the MAX-PC is a great anxiety score if you want to collect data on prostate cancer. So that's a great point because PSA is part of that in [inaudible 00:56:21]. But your bigger, broader question is, how do we prepare patients for focal therapy? Some of my work in active surveillance, which I think is very similar in preparing someone to begin an active surveillance, I think goes hand in hand.

Dr. Behfar Ehdaie:

So quickly, I think you have to normalize the process for patients, meaning you have to understand and feed them right from the beginning, what the expectations are. You're going to go through biopsies. Biopsies are not comfortable. You're going to actually tell me in three years that you don't want to biopsy. I'm telling you now that's what you're going to tell me. So normalizing the process, telling patients that you're not the only one who doesn't want to have a biopsy in three years, many don't, but this is why it's important.

Dr. Tom Polascik:

I'd like to thank everyone. It was a great discussion. I'd like to thank our sponsor, Wasatch Medical again for this program. Our next discussion will be robotic prostatectomy moderated by Ashutosh Tewari, and you can see the speakers. I'd like to encourage everyone who isn't already a member to join the Endourological Society and the Focal Therapy Society. Your membership dues provide you with many benefits, including online access to the Journal of Endourology, et cetera. Finally, we're hoping to have an in-person meeting at the WCET 2021, September 23rd through 25th in Hamburg, Germany. Thank you for your attention.