MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancer Newsline, a weekly podcast series from the University of Texas, M. D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today, our subject is ablative therapies, one of the many treatment options for men with prostate cancer. Our guest today is Dr. John Ward. He is an Assistant Professor of Urology here at M. D. Anderson. Welcome to you Dr. Ward.
Dr. John Ward: Thank you! It's great to be here.
Lisa Garvin: Let's talk about ablative therapies. What does that mean exactly?
Dr. John Ward: Ablative therapies are methods of destroying tissue. It can be destroying in this case tissue within the prostate or the entire prostate or you can use ablative therapies essentially anywhere in the body. It's just what the focus of that energy is.
Lisa Garvin: An ablation means exactly what?
Dr. John Ward: To destroy tissue, to either heat it or freeze it in such a manner that it, the cells are killed and usually replaced by scar tissue.
Lisa Garvin: Now this is something we had discussed a little bit earlier about how ablative therapies have kind of gone through like a wax and wane sort of, you know, thing in terms of popularity and, and standard of care. It seems like we're on an upswing with ablative therapies for prostate cancer. What, to what do you attribute that?
Dr. John Ward: I think a lot of the upswing to the ablative therapies for prostate cancer is the fact that we're recognizing that we're probably over-treating the vast majority of men with prostate cancer. Our treatments for prostate cancer have not changed significantly over the past 20+ years. If you're diagnosed with prostate cancer, the two treatment options remain radical prostatectomy or radical radiation therapy and we've come to realize that there are significant downsides such as incontinence and erectile dysfunction and recovery from those procedures such that we're trying to find ways to treat the vast majority of men with prostate cancer without having an impact on those quality of life issues.
Lisa Garvin: Let's talk about using heat as an ablative therapy and particularly it's called High Intensity Focused Ultrasound.
Dr. John Ward: Correct.
Lisa Garvin: Explain that procedure.
Dr. John Ward: HIFU is a trackless procedure in which a probe similar to what a man will have placed in his rectum for a prostate biopsy is placed into the rectum under an anesthetic and this probe focuses very high frequency ultrasound beams to one point. It's a bit like taking the sun and using a magnifying glass to focus the light of the sun onto one point so that it becomes very hot and you can create a fire that way, that's the same thing that happens with ultrasound. So you take all of those vibrations and you focus it to one point so that you have very high energy dissipation at exactly one point. And then if you take that one point and paint it throughout the prostate, you can ablate all of the prostate or a portion of the prostate, however, you want to, you know, however much of the gland you need to ablate.
Lisa Garvin: Okay, that was my question because in some of the research I've done there's like full HIFU and focal HIFU. What's the difference?
Dr. John Ward: Well, the, the difference is the same as the difference with any of the ablative therapies. You can ablate an entire gland, you can ablate just a portion of the gland. If you, for say, you have a wart on your skin, the dermatologist is not going to ablate your entire skin, the skin being an organ, it's going to, the dermatologist is just going to ablate the wart on the skin. So, and the same thing can be said for kidney cancer or lung cancer or liver cancer whenever we go in to ablate diseased portions of those organs, at times we choose to ablate just a portion of the organ and so for focal prostate cancer therapy that's what we're attempting to do is to identify the major region of the prostate cancer and treat just that region and leave the surrounding structures alone. So for focal HIFU potentially, and again a lot of this is at the, you know, just at the nascent era of development for focal HIFU, the pinpoint ability to deliver that energy might be very helpful for focal therapy and that you can avoid the surrounding structures. When you do whole gland HIFU therapy you do exactly that, you treat the whole prostate and not just a portion of it.
Lisa Garvin: And of course we're talking about a very delicate area because you're near the rectum, you're near the, your urethra, so does HIFU lend itself to working in tight spaces?
Dr. John Ward: It does. The probe, it's, there are some limits of the physics of being able to deliver that ultrasound frequency within the prostate and how big of a probe you can fit within the rectum. But HIFU certainly allows that to be delivered to the prostate and avoid the heat dissipating to areas that you don't want to suffer the effects of high temperatures. So that's nice in that way.
Lisa Garvin: So the procedure takes about one to four hours, kind of walk us through what a patient would be going through in the OR?
Dr. John Ward: Well for HIFU in particular what a patient goes through is a general anesthetic. We then place the patient's legs into a lithotomy position which is your knees high up in the air. We will usually do a proctoscopy just to examine the rectal mucosa to make sure that it looks okay before we begin the HIFU procedure. We then place a probe within the rectum and this probe has two crystals within it. One crystal is to actually image the prostate, the other crystal actually sends the therapeutic sound waves into the prostate. So once that probe is properly positioned and there are some technical aspects of getting that probe properly positioned within the rectum, but once you have that down, then most of the work really becomes at the computer table. You know through the crystal that allows me to see where the prostate is, I'm able to put that into the computer, outline the margins of the prostate and then outline the exact regions of the prostate that I want to have the machine ablate. Once that is all set up and that'll take about 30 minutes, 40 minutes to go through that whole planning, live planning process, then essentially you hit the go button and you allow the computer to go and, and do your plan. Now we oftentimes will break the plan up into segments so that we have to reassess where we are throughout the procedure, but once you hit that go button then it just becomes a monitoring to make sure that the computer is delivering the energy where you told it to.
Lisa Garvin: Now as far as the advantages of HIFU over the standard of care of surgery or radiation therapy, what are some of the advantages?
Dr. John Ward: Well the advantages now, number one, HIFU is not yet approved in the United States, so we have to be careful there in that. The HIFU in the United States is still undergoing registration trials. Neither of the two companies which have developed HIFU machines have actually been able to get through the FDA process, so both, both companies have completed their enrollment to the registration trial - a registration trial being that which is designed to present to the FDA. So both companies have completed those trials, but there is going to be a delay here until the data matures enough, in other words, cancer control data matures enough before they can take it to the FDA and say this is what we can do, we, give us approval to market this and to allow patients to be treated in the United States. Now patients do get treated. United States patients do get treated currently and they're being taken to overseas sites to be treated which the whole medical tourism then comes into all of this. Some patients will go to Europe, while most patients in the United States go to either the Bahamas or Mexico to have HIFU treatment. In Europe though, HIFU's been around for 10 years. It is approved by some of the European Urologic Association groups or at least it is within the consideration of treatment options for some of the European Urologic Association groups.
Lisa Garvin: And I guess our, our, our counterparts in England are a little bit ahead of us as far as data and research.
Dr. John Ward: So, so certainly some of my colleagues in England have been doing HIFU for a lot longer than any of us here in the United States have. I actually work with the world's largest registry of HIFU patients called the Ablatherm Registry which includes a lot of the patients from England and France that have been treated over the past 10 years, it's about six thousand patients and so we write, we've written a number of papers out of that database to report on what the vast majority of patients experience. Now the one, the one problem that I see between what's happening in the United States with HIFU and what's happening in Europe is some of the perioperative care that goes on in that the FDA registration trials did not allow us to perform a TURP prior to HIFU while in Europe the TURP they found they had to do or patients had significant problems with sloughing and urinary tract obstruction.
Lisa Garvin: Explain TURP?
Dr. John Ward: So TURP is the old Roto-Rooter job in which you clean out the middle of the prostate that also helps downsize the prostate. So there's a little bit of a difference in what's going on in Europe and what's been going on in the United States in a way that HIFU is delivered. A lot of the data, you know, your original question was what is the benefit of HIFU over some of the other therapy, therapies and a lot of the data is still maturing, I have to put that upfront. When you, the biggest advantage that I foresee with HIFU is that the recovery time in general is a day. You know it's a same day surgery procedure. You come in, have it done, go home the same day as opposed to surgery which will be one- to two-night hospital stay and about a 30-day recovery or radiation therapy, excuse me, which will require two week, or I'm sorry a, eight-week treatment daily. So it's nice for patients to come in, have it done, and go home the same day, oftentimes with a suprapubic tube in place which drains the urine from the bladder, so catheter to drain the urine from the bladder and there is very little pain if any associated with it. So that's the real advantage of it.
Lisa Garvin: Let's talk about, because I, in some of the research I've done there, some of the, they said that erectile function and incontinence were pretty well preserved with HIFU. Have you seen that based on the data you've seen?
Dr. John Ward: Again, just like with radiation or with surgery, a lot of it depends upon the user and what the, you know, how good the operator of the surgery or the radiation or the HIFU machine is. The experience that I've had thus far with HIFU is that it can go both ways. You know, most of the patients, in fact, all of the patients that we've treated with primary HIFU have maintained their urinary continence very well, which is very impressive. The, as far as erectile function goes we have not been able to treat in a nerve-sparing fashion on the FDA registration trials. Despite that, what I have witnessed is that a lot of our patients will regain their erectile function but in a very delayed fashion. And I, and I sort of put that out there because one of the problems with prostate cancer is there's a lot of marketing that isn't always based in really good science and unfortunately some of HIFU, much like robotic surgery, has been caught up in a bit of marketing that's a little bit ahead of the science and people want to hear these things with continence and erectile function and I think it's important to set proper expectations for what any of these therapies can bring.
Lisa Garvin: Because I've actually seen figures that say 99%, you know, maintain their urinary continence and that just seems a little bit too good to be true.
Dr. John Ward: That's true, as any, any time anybody says always or never, you're in trouble.
Lisa Garvin: And let's go to the other end of the ablative spectrum with cryoablation or the user of cold. What sorts of things are you doing with prostate cancer with cryoablation?
Dr. John Ward: Well cryoablation is nice in that here in the United States it's been around for a long time. Originally, it was done with liquid nitrogen through a much different technique and much more difficult to control and with a lot more complications associated with it. Back in about 1999/2000, they came out with gas driven cryo probes that were now much smaller, direct access, and that you could really control the ice in a much better fashion. So since that time and with the urethral warming device coming back to the market, since that time cryo is becoming more and more popular. The biggest downside to cryotherapy is that a well done full whole gland cryotherapy will destroy your erectile function. So if you're doing whole gland cryotherapy and you have good erections going into it, you won't have them coming out. However, for men who are already suffering from erectile dysfunction who want a same day surgery type treatment that has a very good track record over the past decade, cryotherapy is a very nice option again because it has, you know, no incisions, no significant downtime, good cancer control, good urinary continence. It's just that erectile function for whole gland cryotherapy. But with the cryotherapy being approved in the United States by the FDA, we've been able to extend this concept of treating just a portion of the prostate gland through cryotherapy. So here at M. D. Anderson we're, we're one of the leaders in doing clinical research to better target the tumor within the prostate and freeze that tumor within the prostate to help us achieve the goal of getting rid of the cancer, but not affecting continence, erectile function, or overall surgical morbidity.
Lisa Garvin: Now one of the possible side effects for both of these therapies is a fistula. What is a fistula and is that a major concern?
Dr. John Ward: It's a huge problem if it occurs, haven't, haven't had one, don't want to see one. But it is a problem if it occurs. Luckily with the urethral warming device with cryotherapy and looking at the code registry which again is similar to the Ablatherm Registry and I work with the code registry, which is a registration of all of the patients who're undergoing cryotherapy. The rates of rectourethral fistula in the primary cryo patient population is about 1 in 10,000. So it's a pretty, pretty low rate of having a rectourethral fistula. What a rectourethral fistula is, it's an abnormal opening between the rectum and the urinary tract such that the urine can go into the rectum and the stool can go into the urine and that can cause problems. You don't want those two mixing. So that, that can be a problem, but it's a very limited problem, especially with cryotherapy. With a HIFU it's also been a limited problem on the registration trials, it's been more of a problem in doing salvage HIFU, just as it is with doing salvage cryotherapy. Anytime you're having to use either of these ablative technologies after somebody's failed radiation treatment, the risk of developing one of these fistulas is higher.
Lisa Garvin: Where do we go with HIFU and have you done any here at M. D. Anderson?
Dr. John Ward: Yes, we've done a lot of HIFU here at M. D. Anderson on, with both companies. There is two companies that make HIFU devices and I've been involved with both of their FDA registration trials. So as far as anybody knows I'm the only person in the United States who's using both devices and both companies keep trying to get me to declare one the winner over the other and I refuse. But they are very different devices as opposed to the cryo companies which there are two that make cryo devices which are very similar. The HIFU devices are very different. So we have been participating in both registration trials, the HIFU registration trial for men who've never been treated for prostate cancer is now closed. The HIFU registration trial for men who have failed radiation therapy is still ongoing and we have accrued half of the patients that we need to accrue and we're targeting accruing the second half this year, so that will be, you know, a big milestone. I don't know exactly when the companies will submit to the FDA, but we're slowly getting there.
Lisa Garvin: In closing, Dr. Ward, are you encouraged by what you've seen with HIFU?
Dr. John Ward: I'm encouraged with it, but I still, you know, want to see more data especially with regards to morbidity associated with HIFU. That's you know the ability to control what HIFU and cryotherapy and especially in a focal manner are really competing with is not radical prostatectomy or radical radiation therapy. What HIFU and cryotherapy and especially when we consider both of these and there's a focal HIFU trial coming along also, especially when we start considering focal treatments for these, what it's really competing against is active surveillance is doing nothing for prostate cancer.
Lisa Garvin: Or watchful waiting as we call it.
Dr. John Ward: Watchful waiting, yeah. Watchful, active surveillance, you know, the, the, the dirty little secret is active surveillance is just you know another term for watchful waiting. It has gained tremendous popularity, it's even included in some of the guidelines including the one that M. D. Anderson participates in the NCCN Guideline as a potential treatment option for men with very low risk prostate cancer. However, a lot of men will get the diagnosis of prostate cancer and you sit there and say listen there is, you know, no chance this disease is going to, well there is a very little chance that this disease is going to kill you, you know, I recommend you do nothing and patients don't want to have the C word and not do anything. So that's where therapies such as focal therapy have really taken off, it's not competing with the radical radiation or radical prostatectomy but for those men who want to do more than nothing, but are not willing to take on the risks and see the downside of having radical therapies. So that's, that's what we're trying to figure out is who is best suited to have some form of focal therapy, how best to deliver that, and how to target where the cancer is within the prostate.
Lisa Garvin: And hopefully one day we'll be able to move this to standard of care depending on how it all comes out.
Dr. John Ward: If, if all of our research continues on and we continue to receive funding and support from the community for focal therapy, I think it could be the first real paradigm shift in prostate cancer in 20 or 30 years.
Lisa Garvin: Great! Thank you very much. If you have questions about anything you've heard today on Cancer Newsline, contact ask M. D. Anderson at 1877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in next week for the next podcast in our series.
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