Focal One Therapy | HIFU

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic Podcast for medical professionals. Exploring the latest, innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepard, a medical oncologist here at Cleveland Clinic, overseeing our Taussig Phase I and Sarcoma Programs. Today, I'm happy to be joined by Dr. Christopher Weight. Dr. Weight is the Center Director for Urologic Oncology. He's here today to talk to us about High-Intensity Focused Ultrasound for the treatment of prostate cancer. So welcome Chris.

Christopher Weight, MD: Thank you.

Dale Shepard, MD, PhD: So maybe you could start by telling us a little bit about your role here at Cleveland Clinic.

Christopher Weight, MD: Great. So I'm the Center Director for Urologic Oncology. That means I help oversee the main missions of the clinic as a whole, kind of the educational aspects, the research aspects, and the clinical care with regards to urologic oncology. And so, for those of you who don't know what that means, I didn't say neurologic, which my mom thought that's what I said when I told her I was going to do urology. But that means prostate cancer, bladder cancer, and kidney cancer, which are the three most common, and then some other rare cancers.

Dale Shepard, MD, PhD: I guess we're going to focus today on focal therapies for prostate cancer, and specifically, about ultrasound and High-Intensity Focused Ultrasound. So, maybe you could just give us a really broad background about what kind of focused therapies there are, and then maybe a little bit about the newer technologies.

Christopher Weight, MD: You know Prostate cancer is a very common cancer, and it affects hundreds of thousands of men a year. But most prostate cancer is not immediately life-threatening, may never become life-threatening, but there still is some that is quite aggressive and we still lose 25,000, or so men a year. There've been radical therapies that have been successful for years in preventing death from prostate cancer, but they've also been associated with a lot of side effects. And so, that really allowed a space for people to try to figure out a way to treat this cancer but do it in a way that minimize the side effects that could really have devastating effects on quality of life. And that's where focal therapy has really started many years ago, but now more recently, as we've improved our diagnostic techniques, our biopsy techniques and imaging techniques, it's finding a broader role. And focal therapy could be any sort of therapy that just treats part of the prostate, rather than the entire gland.

The two most common are really High Frequency Ultrasound or HIFU, and Cryotherapy or a freezing and thawing of the prostate tissue, but there are many others, there are some laser focal therapies. There's some gold nanoparticle therapies that are heated up by laser as well. So there is an active area of research and exploration as we've gotten better at identifying where the prostate cancer is, within the gland itself. I'm trying to strike that happy medium of a good cancer treatment that prevents death from prostate cancer, but while simultaneously maintaining a good quality of life.

Dale Shepard, MD, PhD: So we think about the ultrasound technique you mentioned, we'll refer to as HIFU. This is something that's been around for quite a while, is that right?

Christopher Weight, MD: Yeah. I mean, ultrasound is, we've used in medicine for years and years and years, that most people are probably familiar with ultrasound use for prenatal diagnosis and seeing the baby before the baby is born. So it's been used in imaging for quite a long time. And it was realized that these waves could also be focused into a very fine point and that you can really raise the temperature of those cells if you overlap them. And so that has been used also to treat a variety of things, a variety of tumors. But the prostate is a very good candidate for it because you can get very close access to it through the rectal wall, and focus those waves into a really fine pinpoint area. The early attempts with HIFU were really whole-gland treatments actually, not it wasn't thought as a focal therapy and the whole gland was treated.

And when you treat the whole gland, you still get some of the side effects that you'd get with whole-gland treatment such as surgery or radiation. And there are also some limitations, the waves cannot penetrate to a certain depth, so a larger prostates weren't candidates for it. And there were some other limitations, but I think more recently the excitement has been, as we've gotten again better at imaging, and diagnosing and pinning down where the tumors are, of just treating that particular area. And when we do that, then the side effect profile is really pretty minimal. And yet we still, at least in the short and intermediate term follow up studies of these more focal treatments, seem to be pretty good. They're pretty comparable to standard treatments.

Dale Shepard, MD, PhD: So when we think about candidates for this type of therapy, we're primarily thinking about patients that have prostate cancer, relatively low Gleason scores, is that right? Fairly low volume disease. What are the characteristics of patients who would be good candidates?

Christopher Weight, MD: This is a question we get a lot. What are their... I would say shortcoming of the early HIFU studies was that they treated these very low risk men with prostate cancer. And, and we know now that most of those men probably should be watched. So we don't want to treat the lowest risk, but we really want to treat as you transition from the low risk, so that would be a Gleason score of six on the old scoring system or a Grade Group 1 on the newer scoring system. Those, we still prefer to do observation or active surveillance as it is called, unless there are other factors that indicate that this may not just be that low risk stuff and that could be for example, a high-risk Genomic score or certain patterns that are seen under the microscope, or other details along those lengths.

But the real sweet spot for this treatment is as you move into the low intermediate risk, and it's a small volume but intermediate risk tumor, that would be a Gleason score of 7 or 3+4, or a Grade Group 2 on the new scoring system. And the ideal one is actually one that has a corresponding MRI. This shows that the same area that we found on the biopsy corresponds to an area on the MRI, because then we can also observe the treatment effect in the follow-up. And those are the people that seem to do really well, we have more confidence that we treated the area of concern. We have more confidence in follow-up that that treatment was successful because that area undergoes change on MRI that we can appreciate.

Dale Shepard, MD, PhD: How are we incorporating things like Oncotype DX or these sort of predictive tools into selection of patients?

Christopher Weight, MD: One way is similar to what I referred to earlier, just in briefly is that if you have a low risk appearing tumor on histology, under the microscope it doesn't look low risk, but under the Genomics profile like Oncotype DX, or decipher Polaris, there are many that are approved now in this space. If that conveys a high risk, then we think that there's probably more risk in that tumor than we anticipated at, by histology alone. And so that's a good option. And, we were actually really interested in trying to use Genomics as well as potentially Artificial Intelligence to try to re stratify these patients into, identify those that really only have one dominant tumor. Many prostate cancers are multifocal. You may have a dominant lesion over on the left side, but you could also have a smaller lesion on the right side.

But not all of them are that way. And so we think Genomics may play a role in that, as well as potentially radiomics, meaning using artificial intelligence to look at that MRI and trying to sort which ones are truly unifocal and would really benefit from a focal treatment, or those that may be more likely to have a multifocal tumor and maybe would just benefit from a whole-gland treatment.

Dale Shepard, MD, PhD: And so at this point, if there are... You look at a MRI, there are two small lesions, maybe one's on the left, one's on the right, not considering this type of therapy or those that are still maybe under consideration because you have something visible and you still think that there's some discrete lesions.

Christopher Weight, MD: They could be considered. It would be very dependent, also on what the biopsy shows, but they would be considered. We have a group where we evaluate each person who wants to pursue focal therapy. This way, we're trying to keep it rigorous and make sure we're offering the appropriate treatment to patients. So anyone who wants to be considered for focal therapy at Cleveland clinic, we will take the results and evaluate them. We have kind of an ideal candidate, which I referred to initially. And then we have kind of extended criteria candidates that we will consider and under the right circumstances, under the right findings, based a lot on what the biopsy shows we could consider someone in that situation.

A scenario that we feel even more comfortable with is if you have two lesions, but they're both on the same side, then we could do a hemi-gland treatment, which is still associated with fairly few side effects. But then we have more confidence that we're treating most of that cancer there, if not all of the cancer that we can find. We really want to demonstrate success. And, I mean we believe it should work just as well on high-risk tumors, but we just don't want to be cavalier about deploying this technology until we understand it a little bit better and make sure we're deploying it in the safest way for our patients.

Dale Shepard, MD, PhD: When you talk about side-effects, clearly people that get radiation therapy, men that have a prostatectomy are at risk for things like incontinence and erectile dysfunction. Is there the ability to focus the ultrasound therapy? Are there areas of the prostate that you stay away from to minimize those things that are more toward the edges of the prostate, or is it really focal enough that you don't have to worry about that?

Christopher Weight, MD: These nerves that run on the outside of the prostate, we thought as a specialty, we thought it was part of the prostate for probably the first 70 years of doing the radical prostatectomy, we just took them with them all the time because there's that close. They look like they're part of the prostate. They're on the bottom lateral side of the prostate, so on the outside edge, as you were kind of referred to, and it is fairly pinpoint, the area of the ablation zone is kind of one by two millimeters. So it's pretty small. But there can be some thermal spread, so we do try to be cautious in that very peripheral lateral zone, right close to the neurovascular bundles of not giving a large dose there. And for someone who has a large tumor in that space, we just counsel the patient that there may be a little bit higher chance that that particular bundle is going to take a little bit of heat quite literally, and may experience some diminished erection function.

And afterwards, when we look at the results from radiation and surgery, when you're treating the whole gland. It's very dependent on your preoperative function that's very dependent on your age, but it's about 50 to 60% will have their sexual function preserved with those treatments. But it's closer to 90% with HIFU, because it is much more focused and we're often able to treat only one part of the gland. So the other side, for example, may be completely untreated and should function completely normally, as it did before. And with that one to two millimeter margin, if we can have some confidence that that tumor is not budding those nerves, and we can leave just that little zone untreated, and that also translates into better preservation of erections.

Dale Shepard, MD, PhD: What does this look like for a patient? How do you describe what it's like to get this therapy, timeframe, recovery times, things like that.

Christopher Weight, MD: So a patient experiencing this, they actually experienced very little discomfort. This is an outpatient procedure, it is not a surgical procedure. So there are no incisions made. This probe goes in the rectum after they're fully anesthetized and relaxed. And the rectum has to be dilated a little bit to get the probe to fit in. It's kind of like a large bowel movement, a little bit bigger than a finger exam.

And the main thing that a patient experiences is that there is a little bit of swelling associated with this that may block the urethra off. So we have to leave a catheter in place, for anywhere from as few as two to three days. If the zone of ablation is quite away from the urethra, and we don't have to dissipate a lot of swelling, to as many as five to seven days if they have a very large gland and we have to treat a lot of that prostate, and especially if the area we have to treat is quite close to the urethra. But they go home the next day, and very few patients have blood in the urine and they may have a day or so of a little bit of blood when you have your first bowel movements. But many people are back to their normal activities, barring, having a catheter in place within a few days with not a lot of setback or a timeout for a recovery after this kind of treatment.

Dale Shepard, MD, PhD: And success rates so far, you certainly don't have the duration of experiences we do with the other techniques, but how comparable is it?

Christopher Weight, MD: The overall and cancer specific survival are equivalent in the five-year timeframe. We know, in prostate cancer that's an insufficient timeframe. Most studies need to demonstrate 10 year survival to really show that it's better than not treatments. But quite comparable, at least in the intermediate term, in the historical series, it's been around as we talked earlier for 15 to 20 years. You know, when they were doing whole gland, it was not as successful. If the recurrence free survival, I guess, is what we would call it, was more like 80 to 90%. Whereas surgeon radiation were more like 95 to 99%. But in this more focal treatment, when we're a little bit more selective about who we're treating, we anticipate we're going to see a similar success rate, but we don't have that data yet. So we're really kind of in the five-year timeframe.

Dale Shepard, MD, PhD: When we think about this procedure, you mentioned some other focal therapies, things like laser ablation and things like that. Does this an advantage in some way, based on the patient characteristics or the tumor characteristics, or how do you compare those other therapies to the HIFU?

Christopher Weight, MD: Yeah, so this has a real significant advantage, I think over cryoablation, which is again that the freezing and thawing of the prostate. That one is very difficult to control the ice ball. That is so you create an internalized ball with cryotherapy, and is really hard, it doesn't stop along planes. It can go, and that one had actually a very high rate of erectile dysfunction afterwards, even the higher than surgery actually, and radiation. So that one was sort of reserved for people who didn't want to undergo a surgical procedure where radiation wanted a one-time treatment, but weren't really concerned about erections.

Laser therapy is newer and I think still we have yet to see if it will pan out to do quite as well as other focal therapies like HIFU. We have a clinical trial that we're evaluating a laser in conjunction with these gold link nanoparticles. So I would say, the laser is a little bit more experimental than the HIFU, we have a little bit less experience to tell us whether it's going to give us as durable of a result.

Dale Shepard, MD, PhD: How widely available is HIFU?

Christopher Weight, MD: Very widely available in Europe, not very widely available in the United States. I think of the Focal One therapy machines available in the United States, which is the newest iteration of the HIFU device. Yeah, I think there are fewer than 20 around the country. There are more of the older machine called the Ablatherm, which has more limitations, has a less intuitive interface. It's less able to integrate with the MRI. And we feel like less able to target the areas of concern and so not widely available, but I think focal therapy really is going to, we're going to see a lot more of it in prostate cancer because of the benefits with side effect profile. And these are a lot due to the fact that we're getting better at really pinning down where the cancer is.

Dale Shepard, MD, PhD: Are there any issues with the coverage?

Christopher Weight, MD: There can be, yes. It's a significant issue currently. We have, Medicare does cover it. Often, whatever Medicare decides to do, everybody else falls in line, but that's not been the case so far with HIFU. There are only a handful of insurance providers that cover HIFU for prostate cancer. And so that may be a challenge for patients if it's not covered.

Dale Shepard, MD, PhD: So certainly access is going to be important and avail... Not only from coverage, but just availability, but what are the other gaps, what's going to be necessary to move this forward. And I guess the associated question is, what's the next big step? Where do we need to go from here?

Christopher Weight, MD: Yeah, I think that really to get this right now, we estimate probably about 15 to 20% of people might be eligible for this. And I think a lot of it stems on the fact that we don't have good long-term data in the higher intermediate risk or the higher risk patients. So I think research showing us that it's also effective. We don't have any reason to believe that it wouldn't be able, kill a high risk cancer cell just as well as it can kill an intermediate risk cancer cell. So I think we need those kinds of studies. We also need studies to demonstrate that it's at least equivalent on cancer control or at least acceptably not inferior to the existing treatments. And so there are a couple of randomized trials going on right now, the largest one is in Great Britain. Where they're randomizing people to radiation or surgery or focal therapy like HIFU.

We really will be anxious to see those results, because we don't want to see a serious drop-off in cancer control, in exchange for a slightly better quality of life. So I think that's something that's important. And then the other key for HIFU really becoming widespread, I think, is really being able to pin down who are the candidates who are appropriate for it, and who are the candidates who are not appropriate for it. And I think that will come through a variety of enhanced imaging studies, potentially Genomics and maybe AI, helping us to really identify the appropriate candidates. I don't think we'll ever see prostate surgery go away, nor will I think we see radiation go away because they still are very effective treatments and they work really well. But I think as we get better at identifying the candidates who could be treated by focal therapy, and if we demonstrate that it's a really comparable cancer treatment, I think we'll really see it take off in the coming years.

Dale Shepard, MD, PhD: This is great. Well, you've provided us with some great insight today and I really appreciate it. Thanks for being with us.

Christopher Weight, MD: It's my pleasure. Great talking with you.

Dale Shepard, MD, PhD: This concludes this episode of Cancer Advances. You will find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real-time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website at consultqd.clevelandclinic.org/cancer. Thank you for listening. Please join us again soon.