Exploring Focal Therapies for Prostate Cancer

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 Shepherd, a medical oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics program and co-directing the Cleveland Clinic Sarcoma Program. Today I'm very happy to be joined by Dr. Zeyad Schwen, a urologic oncologist here at Cleveland Clinic. He was previously a guest on the podcast to talk about trans peroneal biopsy and advances in screening for prostate cancer, and also to talk about active surveillance for patients with prostate cancer. Those episodes are still available for you to listen to. He's here today to talk about minimally invasive focal therapies for select patients with prostate cancer. So welcome back, Zeyad.

Zeyad Schwen, MD: Great to be back. Thanks for having me.

Dale Shepard, MD, PhD: So, in case people haven't listened to one of the previous episodes, tell us a little bit about what you do here at Cleveland Clinic.

Zeyad Schwen, MD: I'm a urologic oncologist. I treat different types of urologic cancers. I also help in the diagnosis of them. My practice primarily is prostate cancer, but I also deal with bladder cancer, kidney cancer, as well as testis cancer, which are common types of urologic cancers. I do a lot of robotic surgery and other types of surgeries for curing prostate cancer. And we also do some focal therapy here at the Cleveland Clinic, which is another type of treatment for some men with prostate cancer.

Dale Shepard, MD, PhD: Well, as we record this out for everyone to listen to, it's Prostate Cancer Awareness Month, and so we're going to talk about focal therapies for prostate cancer. So, let's start off, what is focal therapy for prostate cancer? What does that mean?

Zeyad Schwen, MD: Yeah. Focal therapy is essentially treating the part of the prostate where the cancer is located as opposed to the entire prostate. So, traditional prostate cancer treatments treat the entire prostate, whether it's surgery, we remove the entire prostate or radiation. Radiation involves radiating the entire prostate. So, it's something that the traditional therapies that we would consider whole gland therapies are different from focal therapies in that we are leaving part of the prostate untreated. And so, the goal is to identify who would be good candidates for focal therapy. Meaning who has prostate cancer localized to a small part of their prostate.

Dale Shepard, MD, PhD: And so, when we think about focal therapies, we'll talk about a couple of specific examples. How new is this?

Zeyad Schwen, MD: Yeah, focal therapy, the concept of focal therapy in the grand scheme of things is fairly new. Compared to radiation or surgery, it's something that radiation surgery has been around for many, many decades. And so, we know the long-term outcomes of these treatments and we know that they're effective prostate cancer therapies. Now, focal therapy has, in essence, been around for around 20 years, and so there've been a lot of different types of focal therapies. A lot of different energies are aimed at treating just part of the prostate. So, we do know that they're effective for treating prostate cancer, but in the grand scheme of things, they're relatively new, but we're not talking about a couple years old. We're talking about over 10 years, closer to 20 years. And so, we do have longer-term outcome data on them.

Dale Shepard, MD, PhD: Which of course with cancer therapies is important, because you want to make sure you have good control.

Zeyad Schwen, MD: Especially with prostate cancer because a lot of the studies look at how effective a treatment or a management strategy is. It has to be beyond 10 years, because prostate cancer moves slowly. So, we don't really know the outcome of a treatment until it reaches that 10-year mark, at the very least.

Dale Shepard, MD, PhD: When you see a patient in clinic, they come to you with a new prostate cancer. What are some of the factors that would go into whether you're going to recommend a localized or a focal therapy versus one of the more traditional therapies?

Zeyad Schwen, MD: So really, it's a very, very important decision, and it's about patient selection. We have to select the right candidate. Prostate cancer, almost by definition, is a multifocal disease, meaning if we find prostate cancer, it's more likely that it's going to be in multiple different locations. And that's because prostate cancer is really a genetic defect in the prostate itself. So, if you've developed cancer in one part of your prostate, you're at risk for developing cancer and another part of your prostate. And sometimes that can be missed, where if we do surgery and we get the full specimen and we think the cancer was really just localized to this one part of your prostate, it's very common to find different foci of disease in other parts of the prostate on the final specimen. So really, it's we got to find candidates for focal therapies in men who are pretty darn sure that the cancer is located in just that one area.

So, we look at the risk of cancer. Is this an intermediate risk prostate cancer as opposed to a high-risk prostate cancer? We try not to do treatment for low-risk prostate cancer. So focal therapy is not the solution for men who would be better served with active surveillance. So low risk cancers are better watched because we know that those don't have the ability to spread. So, there are some out there who have thought of focal therapy as a solution for or a substitute for active surveillance, and that's just wrong. We shouldn't be treating people who don't need treatment. And any treatment, whether it's focal or whole gland therapies have side effects. And exposing those men to side effects is not the right thing to do. So really, it's selecting men who are in the intermediate risk. Higher risk candidates are better treated with more whole gland therapies.

And just because we know that the chances that their cancer can be multifocal or the chances that their cancer could already be metastatic is higher, so you would be undertreating men in the higher risk category. And we do know that the success rates of focal therapies for higher risk cancers is not as good as compared to radiation or surgery or other whole gland therapies. So really finding men who are intermediate risk, who based on imaging, based on biopsies, have the cancer localized to one small part of their prostate. So really, it's identifying men who are good candidates and offering it to them, but with the understanding that, well, one focal therapy has a higher chance of recurrence compared to whole gland therapies. We know this, and it's just because of, well, the nature of the disease.

There are some men who may just have another focus of cancer and another part of their prostate, and so treating that part of their prostate may be an undertreatment, but we also have to appreciate that focal therapies also have less side effects, and as a result, men would have a better quality of life if we are able to successfully treat them with a focal treatment. And there's a lot of different types of focal therapies, and we'll maybe get into that in a moment, but the best way to do it is to do a good risk assessment.

Here at the Cleveland Clinic, we actually consider a multidisciplinary approach for considering people who are good candidates for focal therapy. We actually have what we call a focal therapy tumor board, and we've published on this, and we have to be very rigorous with our selection of men and really in a multidisciplinary approach, meaning we have our radiologists review all the images. We have other urologists who deal with cancer, review the biopsies and PSAs and other types of patient information. And we also have radiation oncologists who do focal therapies for radiation on prostate cancer review the patient. And we've actually found that when we do that, we are only actually selecting around a quarter of the people who are considered candidates for focal therapies as good candidates. So, it's important to be rigorous in our selection of men, but it is an option. And for people who are good candidates, they have good outcomes and a good quality of life.

Dale Shepard, MD, PhD: When we think about candidates for the therapy, you've talked about considerations related to the prostate and the prostate cancer itself. Are there patient factors? We're going to talk about a couple of the procedures here in a minute and what might be involved, but are there patient factors, maybe a patient might be more amenable to doing well with one therapy over another?

Zeyad Schwen, MD: Yeah, that's a great question. And yes, you're absolutely right. A lot of it has to do with what are their baseline urinary symptoms, what are their baseline sexual function, and also what their preferences are. What are their goals? If their absolute goal is by all means treating this cancer, and maybe the side effects are a secondary thought, maybe they're a better candidate for a whole gland treatment versus a focal therapy. If they have obstructive urinary symptoms, some of the treatments can make those worse. So, we consider that as well. And also, what is their willingness to continue to do surveillance? Because part of focal therapy is going to be, well, you're going to have to continue to monitor your prostate because your prostates still there. There's another part of your prostate that wasn't treated. And so, surveilling that part with MRIs, PSSAs further biopsies is a very important part of focal therapy. So, if some men aren't interested in that kind of a treatment, maybe they aren't a good candidate for that as well.

Dale Shepard, MD, PhD: I guess as a medical oncologist, sometimes I remember trying to be the tie breaker and somebody they wanted, there was a surgery option, a radiation option, and sometimes people had this need to know, and for instance, if they had radiation, they'd never know if they had positive lymph nodes or things like that. And so, I guess patient factors are huge.

Zeyad Schwen, MD: A hundred percent. And that's where the regular conversation about what are their goals, what are the things that are important to them, really is the most important thing aside from the cancer characteristics themselves. But that takes time to get a good understanding of that and multiple conversations. Also, second opinions with radiation oncologists are very important as well as a medical oncologist if there's a concern for more advanced disease. And so that's kind of where focal therapy is.

Dale Shepard, MD, PhD: You mentioned that there's a greater risk of occurrence, and that's just kind of a known thing, and we have to assess how much greater the risk is.

Zeyad Schwen, MD: Yeah, that's something that we are still trying to determine. The studies suggest there's about a 10 percent to 15 percent higher chance of a recurrence of prostate cancer. And the recurrence is kind of defined in two different ways. What's the chance that the treatment area has a cancer recurrence that's actually pretty low. It's in the order of around 10 percent to 15 percent infield recurrence, meaning in the treatment zone. But really the more common scenarios that there could be a recurrence of cancer that was outside of the treatment zone, in the area that we did not detect based on the imaging. And so that's where we have to then consider salvage treatments. And salvage treatments, well, they have more side effects because the first treatment, they become additive in terms of what are the side effects, whether how it affects your urine control or how it affects your urinary symptoms or your sexual function.

And so, we try to understand who's the best candidate and really being rigorous in our selection of patients. But the majority of men, over 90 percent of the men who get a focal therapy don't require a salvage therapy. And that's something that is just a matter of trying to identify, is this a recurrence that can be watched? Is this a low-risk recurrence that we can do a surveillance for or is this a higher risk recurrence that requires additional, the, so freedom from a salvage treatment like radiation or surgery is actually pretty good when we do focal therapies.

Dale Shepard, MD, PhD: And when you talk about maybe a little bit more complex salvage therapies may be required, but patients don't necessarily lose treatment options.

Zeyad Schwen, MD: Correct. They still would be candidates for radiation, and they still would be candidates for surgery. They actually would be candidates still for usually a repeat ablation if it's in a location that's reachable or favorable for a repeat ablation. But we just have to understand that that will be likely to cause more side effects. So, radiation may cause more irritative symptoms, more obstructive symptoms. In a salvage situation, a salvage prostatectomy may be a little bit more challenging to do because of scar tissue from the original ablation. And so, the chances that we would be able to preserve your urine control as well as your sexual function may be reduced. So, there's a little bit of an additive effect from the side effects.

So, we shouldn't be thinking, oh, let's just do this ablation because we have a backup plan. We shouldn't be thinking of focal therapy that way. We should be thinking of it as the goal is just this treatment. But it is reassuring to know that there are backup options still with the hopes of curing the cancer, even in the event of her occurrence. And so that's something that we do talk to patients about.

Dale Shepard, MD, PhD: Excellent. Well, let's talk a little bit about what these procedures are, what these focal therapies are. Tell us a little bit about nano knives.

Zeyad Schwen, MD: So, this is a newer technology, a newer energy of what we call electroporation. So, what we do is we deliver high voltage current across the prostate tissue, usually in the form of a needle that disrupts the cell membrane of the cancer cell, and then causes cell death. And so, they call it electroporation, essentially, it creates pores in the cell membrane, and then as a result, the cell dies. And what's good about nano knife, which is the term that people use, is that it can be directed in a focal way, but also it reduces the collateral damage of the normal tissue around it, so it has less collateral damage than some of the other energies that we have.

So nano knife, another advantage of it is that we can deliver it to other parts of the prostate that were difficult to reach with other focal therapies like the anterior prostate. So, the top of the prostate traditionally was difficult to reach with some of our other focal therapies like HIFU, which is an ultrasound ablation, and a lot of these have to be directed through the rectum. So, reaching the top of the prostate is sometimes more challenging, and sometimes the urethra is in the way. So, the nano knife is another type of energy that allows us to deliver that energy to a focal part of the prostate at the top that would be difficult to reach with HIFU.

Dale Shepard, MD, PhD: When you talk about collateral damage, I guess the thing that would come to mind would be nerves that have to do with sexual dysfunction and things like that.

Zeyad Schwen, MD: Yep. And that's something where we think of a number of different anatomic parts that we're trying to avoid injuring. The nerves that supply your erections, which run on the outside of the prostate. That's one of them. Also, your urethra. We don't want to cause a stricture in the urethra, which is another risk when we're doing any sort of ablative therapy of the prostate, your sphincter muscle, which is another important muscle that helps you control your urine. We also don't want to damage. So, we think about these three major anatomic landmarks as far as trying to avoid injury to surrounding structures.

Dale Shepard, MD, PhD: Are there size limitations on how large a lesion in the prostate can be to get this procedure?

Zeyad Schwen, MD: Yes, exactly. And that's something where the larger the tumor, the more likely it's going to be difficult to treat with focal therapy. A lot of it determines is does it cross to the other side of the prostate? Is it a large enough tumor that it essentially is also involving the opposite side? And then we start to ask ourselves, well, one, we know with larger lesions the chance of a recurrence is higher, and would they be better served with whole gland therapy as opposed to focal therapy?

And so, it's something that we look at the size, we look at the other appearance on the MRI, is it extending outside of the prostate or are there signs of extra prostatic extension? These are things that are risk factors for failing focal therapy. Also, biopsy information. Are there certain features of cancer that we know don't respond well to focal therapies? So size is part of it, and really looking at some of the other markers that we have together. So that's kind of where also a tumor board discussion having, discussing it in a multidisciplinary way has benefits to selecting these men and taking into account all the features.

Dale Shepard, MD, PhD: Another procedure you talked about was using HIFU. Tell us a little bit about HIFU and kind of what that entails and maybe pros and cons.

Zeyad Schwen, MD: Yeah. HIFU is called High Intensity Focused Ultrasound. So, it's an ultrasound ablation of the prostate, and it's actually one of the most widely used focal therapies, and it's one of the first focal therapies that were used. There are other types of ways that we can deliver focal energy and others is cryotherapy, which is where we use freezing energy to kill the prostate cancer that we can direct focally as well. But HIFU is an ultrasound ablation. We know that this has the ability to kill prostate cancer and also can be directed in an image guided way. So, we use ultrasound guidance, and we can also use an ultrasound and MRI fusion guidance to ablate the prostate in the lesion completely. It has a good effect in terms of killing the tissue as well as sparing the surrounding nerve structures as well as the urethra and the sphincter.

But some of the limitations, as I kind of alluded to before, is it can't reach the entire prostate. It sometimes can have difficulty reaching the top, and if the urethra could be in the way, we don't want to ablate that or if it's near the sphincter, we don't want to be ablating that. So HIFU, we deliver them. We do this procedure in the operating room, but it's outpatient. You have to wear a catheter for a couple of days just because there can be some swelling in the prostate, but very minimal pain, very good side effect profile. But it is a focal therapy, and we are limited by the ability to compare to whole gland therapies have equal cancer outcomes. So, we do have to continue monitoring.

So that means checking your PSA and checking the MRI to make sure that the lesion is ablated and not showing any signs of life. Making sure there's not any new lesions in the prostate that popped up since. Then, usually around the one-year mark, we do a prostate biopsy to make sure that the cancer's gone. And so sometimes we see the PSA rising and we can do the biopsy sooner, but we just as a routine standard practice, we biopsy people at the one-year mark. So that's kind of part of the buy-in for any focal therapy. But HIFU is probably the more commonly used focal energy.

Dale Shepard, MD, PhD: But as you say, things like nano knife, location of tumor might have some benefit. How widely available are these therapies?

Zeyad Schwen, MD: Well, they're becoming more widely available, and a lot of it is patient driven. Patients don't want to be exposed to the side effects of treatment. And so, they're willing to kind of seek out these focal energies. And as we study them more and we understand who the right selection are, we offer those to people. But there are some who are offering those focal therapies in a way that is exposing everybody, all comers to focal therapies when they would've maybe better treated with radiation or surgery. And so, it's something that there are some who have misused these treatments, and so there are certain locations that people travel to out of the country and other states that may be using them in an irresponsible way.

And it may be people who have been better served with surveillance are being exposed to these treatments and negatively impacting patients. But centers that offer focal therapies in a more responsible way, in a more selected patient population, they're becoming more prevalent in large academic centers. Other private groups in the area also are offering focal therapies as well, but there's some who are also using it as a financial incentive to treat people who can otherwise be managed in a better way.

Dale Shepard, MD, PhD: So, are we doing any clinical trials with focal therapies?

Zeyad Schwen, MD: Yeah. There's actually one that we're doing here at the Cleveland Clinic that involves focal surgery and comparing it with the HIFU ablation. So, Dr. Jihad Kaouk is going to be the one leading that trial looking at new robotic surgery using the single port robot. That is a way to use surgery in a focal way that can reduce the side effects and similarly treat people who are good candidates for focal therapy. So that's something that's being done with also Ruben Olivares, who's one of our experts in focal therapy here at the Cleveland Clinic, and that's something where we're accruing patients and we're going to hope to see results and see if focal surgery is a good option. In the armamentarium for focal therapy.

Dale Shepard, MD, PhD: I guess essentially at large academic groups, the larger urologic practices, things like that would be able to offer these sorts of procedures. Are there particular patients that would be best suited to come to a place like Cleveland Clinic or these centers that do these more often? Is there a characteristic of the tumor, a patient that really should consider that?

Zeyad Schwen, MD: Yeah, I think that what's great about the Cleveland Clinic and the way we deliver focal therapies or offer focal therapies is we're very rigorous in our selection, and that's not something that you would get from other locations that might be financially incentivized to offer focal therapies to all comers. We have excellent multidisciplinary care here, and so we rely heavily on our radiologists to help us select who are good candidates for focal therapies. So having that expertise here at the Cleveland Clinic, Andrei Purysko is an excellent radiologist that we work with frequently. Another great radiologist is Ryan Ward. These are our expert GU radiologists who help us select patients and identify distance from important structures, characteristics of the tumor that could be worrisome.

And also, we rely on our radiation oncologists to provide second opinions for who would be good candidates for radiation as well. So that's something that at the Cleveland Clinic, we do have that other places may not, but other centers are also responsibly offering this therapy, and it's something that really, the other advantage is we're continuing to study the outcomes of this newer therapy and how it compares to whole gland therapies that are more traditional. And so, tracking our own outcomes is another thing that we're hoping to do, and we're researching this routinely and trying to update what we're doing in terms of are we doing the responsible and correct treatment for cancer?

Dale Shepard, MD, PhD: Excellent. Well, you've provided some outstanding insight for us today. Appreciate you being with us.

Zeyad Schwen, MD: Great to be here. Thanks for having me.

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