S3 E11: iMRI as a platform for interventional therapy

Recorded live from the cook booth at SIR and featuring leading experts in the field of interventional radiology discussing a wide range of IR-related topics. This is the cook at SIR Podcast Series. Good afternoon, my name is Joshua Krieger. I'm the Director of Product Management for Cook Medical's new IMRI division. I'm joined today. I have the pleasure of being joined today by Dr. Juan Javier de Loche at a Urological oncologist out of the University of California, San Diego, who specializes in prostate cancer. Thank you so much for joining me today. Thanks so much for having me. So looking forward to a really good conversation today around the utilization of MRI as a part of therapy, drawing from some of your experience with that. Excited to get your perspective. You know, we're sitting here on the floor of SIR. And I love your urological oncology background and I'm interested to learn more about how you interact with some of these therapies. So thank you so much. I wonder if maybe as we get into it, it might be good to give us a little bit of background on yourself. I wonder if maybe we start with some of your educational background just to understand where you're coming from and the perspective that you've got. Yeah, of course. So my initial interest in prostate cancer probably developed as a medical student, I went to Brookers, New Jersey Medical School in Newark and went on to do my residency training at Yale New Haven Hospital in Connecticut. And when I was a resident, I had a very strong desire in prostate cancer and my mentor there had a real interest in focal therapy. And after residency, ultimately decided to do a fellowship at the University of California San Diego. You know, they were kind enough to hire me on after to be a faculty member there. And through all those experiences, really kind of developed a niche or interest with them prostate cancer and focal therapy type of treatment. I think that's fantastic. You know, I wonder if it might also be good to just get a little bit about your practice today. What does a typical day is never typical, but across a week, you know, what does a typical week look like at your current practice? Yeah, so I think my practice is evolved over time. You know, I think one of the things about fellowship training, a lot of the fellowship trainings is really a big emphasis on prostatectomy and removing the prostate. And you know, it's a little bit unique in my residency training that I got some exposure to it's a focal type treatment. In terms of my day to day practice, I do about two days of research, sorry, two days of surgery. One of them is major surgery, generally radical prostatectomy. And then one of them is minor surgery, which is typically transparent prostate biopsies, focal therapy procedures, and then rectal spacers for patients that are getting radiation. And then I have two days of clinic. And then I do one day of research focused on outcomes related research that's funded through the NCI. Fantastic. You know, I wonder if you could maybe go into focal therapy is something we're going to talk about a lot about today. You obviously see the breadth of treatment and not every focal therapy is going to be right for every patient. What really drew you into wanting to be able to provide focal therapy? It's probably a patient case. When I started as an attending, I wanted to be able to offer the best available treatment option to patients, irrespective of whether it was surgery or radiation or something else. So I wanted to play a part in their treatment, whatever they decided to do. And one of the things, I remember the first prostate cases, prostate communications I did, as a guy was in his, or a gentleman in his 60s, a little bit of erectile dysfunction. No problems urinating. He had grade group three prostate cancer. So slightly more aggressive, but still intermediate risk. And you look at the NCCN guidelines, they recommend radical prostate treatment, take the prostate out or radiation. So I did a prostatectomy on them. And at the end of the case, or at the end of the, some about seven days later, and fortunately no erections, leaking a little bit. Path looks good. And I look at the path. And the path says, stage two prostate cancer, negative surgical margins, always important for surgery. Negative lymph nodes. You got down stage to grade group two disease. And I was like, oh, it's pretty good. And then the thing that really kind of shocked me was they look at the two, the whole prostate and they determine how much cancer is within the prostate. And I said, one percent of the prostate has cancer. So I'm thinking to myself, this gentleman is now completely impudent for a milliliter of prostate cancer. Took the whole prostate out because that's the guidelines you. And never regained his sexual function. Real PSA undetectable now, several years later, doing well. But it led me to believe that we really need to do prostatectomies on every single patient. We do about 100 prostatectomies a year. There are a number of patients I see on a day-to-day basis that need prostatectomies. Patients with cancer extending outside the prostate, T3 disease, high glicens cores, at least in 10, at least in 9 things we're very concerned about. A weird variant, histology for prostate cancer, those types of patients, we're very concerned about neoprostatectomy. So that still makes up a large bulk of my practice. But the focal therapy component of it, you know, started to go into how can we preserve patients the way that they are and cure their cancer. Or potentially cure their cancer for a prolonged period of time. And that's where I started investigating different types of focal therapy procedures. I had trained on some as a resident and then as a fellow, or excuse me, as an attending, began to seek out mentorship beyond my institution. Because I didn't really have a lot of mentors at the time that were focal therapy oriented within the university. It's amazing to me. I mean, we can talk about some of these things academically, but when it comes to that patient and their story, it really brings into relief the value of some of these new therapies, things like focal therapy for people to be able to one live cancer free, but also then to have their life less changed by the process of that treatment. I really appreciate you sharing that. You know, as you think about your journey with focal therapy, with the biopsies, one of the things we're talking about at this show quite a bit is the inclusion of MR as one of those primary visualization modes. You hear it, medical, we've got one of the brand new MRI suite built into our booth here. We think there's real value in the intervention under MRI. I wonder if you could speak just to MRI and as you look at both diagnosis and then also biopsy and therapy, what MRI provides you in addition, not in replacement of, but in addition to the other imaging modalities that you use. Yeah, MRI in my mind has been revolutionary for prostate cancer. You know, earlier today I gave a podium or a post-recession here, podium. Presentation on the work of proprostate cancer and what has really changed prostate cancer is the integration of MRI that's soft to shoot definition. You know, where is the prostate cancer? You know, we have historically thought of prostate cancer being within the peripheral zone that's the outer part of the prostate. But I can tell you that I probably see about two to three second opinion prostate biopsies a day where patients that have had prostate biopsies before, never had an MRI and invariably 95% of them have disease outside the peripheral zone, usually in the transition zone, and identifying those cohort or patients in addition to identifying where to biopsy within the peripheral zone has been really critical in terms of the accurate diagnoses of prostate cancer. I had been introduced to MRI as a resident. One of my mentors was very, very focused on training residents to use the Artemis system at that time. And the learning curve was probably the biggest factor in educating urologists on how to use an MRI. And as I got on in my training and I went into fellowship, I found myself really needing to know how to read the MRI myself. I couldn't just always rely on the radiologists because I was now the one doing the biopsy, whether it be cognitive or whether it be software fusion. And I took it upon myself to spend some time with the diagnostic radiologists. And they were kind enough to go through the different phases and I slowly educated myself on how does the MRI machine work? You know, the differences in the Tesla magnets. the actors. of the MRI in terms of determining whether or not we could find prostate cancer limitations and then reading the certain sequences because that is really probably the most critical part of doing any sort of MRI-based procedure. An MRI I think will continue to play a critical role going forward because of that definition planning. I get an MRI on every single patient that we're thinking about doing a biopsy. I make sure we get an MRI within six months of any prostate-related intervention. So that is focal therapy or prostatectomy because I highly, very highly use that to guide the nerve spare if I'm doing a prostatectomy. I can tell you, you know, one of the things that's been talked about in the MRI literature is inner observer variability amongst radiologists and I can play a number of patients that probably had T3 disease and depending on where the MRI was read, it just wasn't picked up. So really, really critical to be able to interpret the MRI yourself and then act upon it. And for focal therapy, focal therapy planning in terms of where you're going to do the ablation. And you know, we had looked at the MRI suite today within Cook and it is very much reminds me of the fluoroscopy suite that we commonly use in neurology. In neurology, we do a lot of fluoroscopic procedures, whether it's stone disease or interstem or some of these other procedures. And it is very, very cumbersome to sometimes get the fluoroscopic x-ray machine into the room, depending on the room size, x-ray, tech availability. And it is basically another evolution of that machine. And I think we'll be having a central role really in prostate related procedures because of that need for MRI and prostate related procedures going forward because that is really the basis of really every prostate procedure I see going forward. And I think just to give a little bit of additional context there, we're sitting here at SIR. We've just in collaboration, Cook and Siemens and many of the decisions that we work with launched an MRI suite. The ability to have a turn key set up where it is truly an interventional space. It's not a diagnostic space retrofitted with some accessories, but an interventional focused space with that floor planning with the sterility, the workflow with NMR as that primary visualization to center. And it's something we're really excited about. I wonder if you could tell us a little bit more about what your current work with in more focal therapy is and just give us a little background on that. So at UCSD, we would have been investigating different types of focal technology that we can use. And about three years ago, there was a large interest in integrating the profound Tulsa machine into our focal therapy armamentarium. And it's complex in a sense that you need an MRI, you need an anesthesia. I had really, even though I discussed earlier, I was familiar with reading MRIs. Was not familiar with how to run an MRI machine or even working within one. And while it seems like amazing technology, I think at first was a little intimidating. So I would admit that I was quite intimidated initially when I had heard about Tulsa and all of the things that I could do. So we started, so when we met with profound, they were very welcoming and very innovative in terms of their ideas and things we could do. And now we're really looking for partners within the university who could help guide us and people that had some background in CT or MRI guided procedures. So fortunately, our interventional radiologists, there were a couple that had an interest in partnering with us. And partnering is really need two things. One of them is they need to be interested in doing it. And the second thing beyond interest is you need the time to do it. Because as you know, we're all busy, you know, I said earlier, you know, four days clinical, you know, I have a, you know, this NIH funding that takes up a lot of my time. So finding that time is really important and a good partner that's reliable where you can both have the time to meet with the patient prior to the procedure, both be there for the procedure and then guide the patient afterwards. That was the beginning of our journey. And then from there, fortunately, profound was very helpful in identifying which magnet we could use because not all magnets are compatible with the machine and the complexity of which magnet is the most appropriate for the machine is a little bit beyond me. But, you know, profound was very helpful in identifying what are the magnets that are central candidates for use. And then for us to identify, is it, does that magnet have the time to do the procedures? It's not just our time, it's the magnet's time. The magnet, as we talked about earlier, is used for lots of diagnostic procedures. Well, I'll be on prostate cancer. So that is how the partnership form and then we started with a workflow and developed basically a pre-op system where we would have the interventional radiology nurses pre-op the patients, bring them to the diagnostic MRI radiology area, prep the patient. Our anesthesia team would be there. It would place the patient under anesthesia. Our involvement is we would, at the start of the case, I should say, would place the endorectal cooling device and then the UA, the urinary apparatus into the prostate. And then we would be involved throughout the case in terms of the ablation planning along with our interventional radiologists who continue to have expertise within that field. It seems like that collaboration has really been central to this. And I wonder if you might expand on that collaboration and if somebody doesn't have that and maybe interested in the future, some thoughts on the value of that collaboration and ensuring that it's being set up well and forming that law. Yeah, I think kind of the key is that it's not a competition between you and interventional radiology, although I realize it's some institutions that can be the relationship and that it's what's in the best interest of the patient. Sometimes to form the collaboration to bring in different expertise. While I read a lot of MRIs and I feel very confident in reading them, some interventional radiologists will have experience beyond them in terms of their knowledge of MRIs. But interventional radiologists may not have the cancer related knowledge in terms of selecting the best patients for treatment and then ultimately following the patient in the long term and counseling through that process. And we're very lucky because as I mentioned earlier, largely the support staff for these procedures are fired up through interventional radiology. And it is their nurses, their techs, and is their anesthesia time. It's their anesthesiologist who is not doing an IR related case who's helped supporting us. So cultivating that relationship has been essential in order to continue the program going forward. And I'm sure there are times when maybe not all of us are available, whether it's either of us and we're always trying to make time to do the surgeries. It's really neat to see that multi-specialty collaboration really around improving patient care and changing having that really world-class care around the cancer therapy but also then preserving the rest of that patient's life. Across your time, I wonder if you could speak to how you've seen the space evolve. I know that you've been working with profound for about three years now, but your career spans a little bit longer than that. How has this evolved? And if you're looking out to the next five years, how do you see it continuing to evolve? What are the things that you're excited about that we need to be doing research into and continuing to improve? Yeah, going into patient selection and counseling, I think that the success of a lot of focal therapy is on patient selection. And I went back to this paper that I wrote three, four years ago now. And it was on, who is the best candidate for focal therapy? We published it in prostate cancer and prosthetic diseases and I'm reading through it. And I'm thinking, I've really expanded the criteria of who is a candidate. Because-- and the reason why I've expanded that criteria is because the patients that were getting treated was so successful that I thought I could continue. And I have expanded it to patients that are kind of like those borderline candidates who have also had a lot of success. So treating the whole prostate or a majority of the prostate was something that we really were not knowing when we first started. Treating more than one lesion within the prostate is something that we really were not doing before and that we're doing now. The one nice thing about the profound system is the real-time monitoring of the heat now within the prostate. We say that we believe that 60 degree Celsius is likely the critical temperature needed to destroy the prostate cancer cells. And you really don't know that unless you measure the temperature. Otherwise, you're just guessing. And I think that a lot of the prior failures in some of the cases with some other technologies is due to the fact that we're really not getting to the lethal temperature necessary to treat the prostate cancer cells. And that is another positive component to incorporating MRI as it gives you that. It gives you a dose-related response. You can see the dose of treatment that is getting, even if it is potentially borderline, the ability to go back and treat the tissue again. In terms of where I see this going forward, the procedure will probably increase in the time length. So right now the procedure runs a bit long, but it's not too long, and it is getting faster compared to where it was. I mean, there have been a number of integrations, the boost technology, AI, into getting some of the parameters inserted into the computer, or the software readily available. We'll continue to speed up the process. But ultimately, I can tell you, I did one day, maybe a month ago, where at 100 gram prostate and the case went in an hour. And the reason why was because the prostate tissue just heated very quickly to the lethal temperature necessary to kill the cancer cells. And then the subsequent case, quite slow. But largely a reflection on how the tissue handles the temperature. So I think that that will likely be the next evolution is how to make that longer case a quicker case and how to get to that lethal temperature at a faster pace. What will probably be the next evolution of these technologies going forward. And MRI, I think the MRI suite is appealing in terms of cutting down on another level of logistical burden within setting up the patient and getting them ready for it. And availability of the machine is a big driving factor. I look at how many cases I was doing. It was one a month, sometimes every other month, because we only had one day to do the procedures. Because of the success of the program, we now have one day a week where we can do the procedures. And actually, there's one week rated to a week, two days a week. So availability of the machine, I think the speed of the procedure will probably be the next boundaries of where to go with a lot of this. It's amazing that we've got such wonderful efficacy that we now get the opportunity to work on things like efficiency. I think you mentioned there the thermal mapping and thermal disseminatory. And that's something that, as I think about where some of this goes with hemorrhagic visualization, we're just scratching the surface of the amount of physiologic information you can get out of the machine that you can query it with and get wonderful answers back. I think there's a host of research that can be done digging into how do we understand when a therapy is truly complete, how do we get the appropriate margins and spare tissue that doesn't need to be taken away. And I think that the emore does that in a way that other imaging modalities, because of how they operate on a physics level, just are not providing back that information. Yeah, visualization of the neurovascular model, really, really critical. I mean, where the neurovascular bundle is and where you can see it is on MRI, as single-handedly changed my outcomes for return of erectile function after prostatectomy. And it has also played a critical role in the use of focal therapy in terms of planning, because not every patient has their neurovascular bundle in the same place. I mean, historically in neurology, we were taught that it is postural lateral. And you will see-- I mean, when you look at the MRIs, when you do the prostate ectomy, I mean, the neurovascular bundle, it can run right under the prostate. It can be a right posterior, and just kind of guessing where it is, sometimes when you're doing some of these procedures is not adequate. And to your point, I think critical identification of this fincter, how low you are on the prostate to make sure you're not damaging the externally resource fincter, and then secondarily paying attention to the bladder neck, and in location to the remainder of the prostate. So you don't get a bladder neck contracture, a bladder injury. You know, I wonder if we have come a tremendous way. They were still further to go. I wonder if there are in your mind still some gaps, or some areas where additional research might be focused to high value, perhaps beyond even just that gain of efficiency. Is there anything that comes to mind? I think that the concept that all tumors will respond to heat or cold or electrical current as a solitary treatment is probably not true. And there probably needs to be further investigation to additive therapy, in a sense, that patients may benefit from focal therapy plus some additional treatment, whether it's hormonal therapy, a systemic agent that targets a specific mutation. You know, there's a trial looking at focal therapy plus low dose radiation, and using it concurrently to decrease the rate of recurrence. Because for reasons that we don't understand, tumors behave very differently, or certain tumors are heterogeneous, and within that heterogeneity we'll respond differently to a glacier. For some tumors that respond amazingly to it, and they'll see a great response. Other tumors that kind of just decide to hang around, and there's clearly some sort of mutation going on there that is driving the recurrences. So adding an agent beyond that will probably be the next frontier of focal therapy. I think that the technologies in themselves are doing amazing, but probably need some additional help. You know, I think about just adding on that. As we continue to push, it's you and your colleagues continue to push that focal therapy closer and closer to sensitive structures, structures that you want to spare, the ability to have those combination therapies to fully take out disease, but remove initial work with the focal therapy. You know, I wonder we've had a fairly wide-ranging conversation today. I wonder if there's a, you know, if someone is out there as listening, says, you know, this all seems interesting. If we could come back to one of those cases, examples that really highlights for you the effects to your patient of being able to have this real-time thermometer, and the focal therapy. I wonder if there's a second case that comes to mind. Yeah, you know, the second case that probably comes to mind was slightly different patients. So not all patients can undergo radical prostate effect to mean, and some are quite fearful of radiation. And there is still a group of patients that they want to do something, and they don't know should they pursue active surveillance, should they do some sort of treatment. And they don't have an imperative, you know, indication to operate, but they may benefit from treatment. And the reason why they may benefit from treatment is really the size of the lesion, and the growth of it is unknown, and the larger the lesion gets, I think the less likely it is to respond to focal therapy. So the other case that comes to mind probably is a patient in their 50s, who similarly had great, was this great group, two disease, with a PSA of five. And actually saw a rapid progression of the lesion size, and ultimately benefited from the focal therapy, but in the end had the same outcome. To anyone listening out there, you know, in terms of, you know, adopting a new technology, I think that's probably where I can give the most guidance. When I was a resident, I had all this anxiety that I wasn't Get it, get it, get it, get it. good enough training and that I wasn't going to learn everything that I could to be successful as an independent attending. And I had this one mentor who was learning whole-up, which is something completely different. It's laser-annuculation of the prostate for BPH. It's an alternative to turp. And he told me, "If you want to do something and you don't know how to do it, you go out when you learn how to do it. Get a proctor, he comes to the surgery, you go out there, you watch the cases, you work with the company, you demystify the procedure. And if you look at many of the doctors now that do robotic surgery, the ones in their 60s, they didn't learn robotic surgery when they were residents because there was no robot there. And I think that this evolution of technology that we're using for prostate cancer is much like that. And that has been my experience is to go out, get a proctor, go observe some cases, and take the initiative to learn it because I think it will benefit not just for patients, but it will benefit the future of prostate cancer treatment." I think that's just a phenomenal place to leave it. I appreciate that advice to a resident, but also to an attending right now who is wondering what is there in other therapy and other service line that I can be able to provide my patients beyond what I'm doing today. I really appreciate our conversation today. Thank you for your time and for all of you out there. Thank you so much for listening. Thanks so much for having me.