Focal therapy for prostate cancer

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When treating for localized prostate cancer, surgery and radiation are usually what people hear about. However, there are other treatments that could be options under a heading of focal therapy.

Dr. Andrew Wood, a urologic oncologist with the University of Michigan Health Rogel Cancer Center’s Weiser Center for Prostate Cancer talks about these options and which patients could benefit from them.

Participant:
Andrew Wood, MD

Transcript

Scott Redding:
Welcome to the Cancer Aware Podcast, where we'll discuss cancer prevention treatments, the latest in research and important news around cancer, brought to you by the University of Michigan Health Rogel Cancer Center.

Today we're talking with Dr. Andrew Wood, uro-oncologist at Michigan Medicine, about treatment options for prostate cancer patients.

Welcome, Andrew. We hear so much about prostatectomies, mainly robotic these days, radiation therapy, and even watchful waiting for localized or early-stage prostate cancer. Outside of that, are there other treatments for patients to consider?

Dr. Andrew Wood:
Yeah, great question, Scott, and thanks so much for having me here on the podcast. I've been looking forward to it. So you mentioned really two different, very different strategies. One being what we call active surveillance, which is for men with low-risk prostate cancer, following them over time, not choosing a treatment plan upfront. And then patients who get whole-gland therapy for their prostate, meaning we either remove the entire prostate or we treat it with radiation. There is an emerging third treatment strategy that actually involves treating only part of the prostate, only the part of the prostate that contains the cancer, usually as seen on a prostate MRI, allows us to leave the rest of the prostate alone, and because of that, substantially reduce the side effects that patients are going to experience.

Scott Redding:
So what are some of those treatments that just focus on that part that minimize the side effects?

Dr. Andrew Wood:
Yeah. So there's a few different kinds of modalities that we use to try to, essentially they're all killing part of the prostate and they do it in various different ways. One is called HIFU, which stands for high-intensity focused ultrasound. Another is cryotherapy or cryoablation. Another one is irreversible electroporation, also known as NanoKnife. And they all use different kinds of technology to be able to do what we talked about, which is to, in a very precise way, destroy just the part of the prostate where the cancer lives, leave the rest of the prostate alone, importantly, leave the nerves that run adjacent to the prostate generally alone and leave the urinary sphincter alone. And by being able to spare those structures and spare at least half of the prostate, we spare patients from a lot of the significant side effects that they may have with radical prostatectomy and radiation.

Scott Redding:
Can you explain a little bit more about HIFU?

Dr. Andrew Wood:
Yeah, absolutely. So HIFU, as I said, stands for high-intensity focused ultrasound, and it was developed initially in the 1950s and '60s. So actually, the technology is not that new. The way we're using it is quite new. So HIFU uses high-intensity ultrasound, many times more powerful than a regular diagnostic ultrasound, to generate heat in the tissues in a very precise location. And we can use that to essentially draw a boundary around your cancer and be able to kill with heat that entire area. So it raises the tissue temperature to greater than 60 degrees Celsius, which is sufficient to induce cell death in region.

Scott Redding:
So just out of curiosity, how is that different than a targeted radiation therapy?

Dr. Andrew Wood:
Yeah, great question. So most targeted radiation therapies that you hear about these days, things like CyberKnife, SBRT, they are advanced ways to still target the entire prostate. They do a much better job of avoiding any adjacent structures like the bowel or the bladder, but they still are treating the entire prostate. The way we're primarily using HIFU at the University of Michigan these days is to actually, again, do something called focal therapy like we talked about before, which is this idea that we're only treating part of the prostate and leaving the rest of the prostate alone. So those radiation therapies have been wonderful advances in treating men with prostate cancer and they've reduced side effects from radiation. However, they do still have the limitation that they are treating the entire prostate. So focal therapy with HIFU is different in that way.

Scott Redding:
You also mentioned cryoablation. What exactly is that? Is that like freezing the prostate?

Dr. Andrew Wood:
Yeah, it's exactly like it sounds. It is actually, it's putting a probe inside and then freezing the surrounding tissue around the probe. We use liquid nitrogen to do this, and we can see an ice ball actually expand as the liquid nitrogen is injected into the tissue. We use things like urethral warming catheters and rectal warming catheters to prevent that cold from getting anywhere we don't want it to be. But it's another technology that we sometimes use for focal therapy. Again, just the treatment of only part of the prostate. We use it a little bit less than HIFU these days because it's best for tumors of the anterior part of the prostate, whereas HIFU is best for posterior tumors of the prostate, and there just happened to be more tumors in the posterior part of the prostate. So it is an option, but I would say we use HIFU a little bit more these days.

Scott Redding:
If we're doing the special targeting, whether it's freezing or whether it's heat with the HIFU, what is the appropriate patient to consider this? And is there more chance for recurrence down the road with only treating a portion of the prostate?

Dr. Andrew Wood:
Yeah, great question. So I'll start with the second part of your question first. There is, of course, definitionally a little bit of a higher risk of recurrence in the part of the prostate that was untreated. Right? So when you do radiation or surgery, we're treating the entire prostate. In this case, we're leaving part of the prostate, but that's why we put patients on a very clear surveillance schedule so that if this cancer comes back in the part of the gland that was untreated, we catch it and we treat. And many of those patients can actually get another round of ablation rather than having to go onto surgery or radiation. So in terms of success rates, we quote patients that, at about five or six years after their therapy, 80% of those patients will not have had a recurrence that requires them to go on to surgery or radiation.

And then the first part of your question, and I'm so happy you asked this question because this is really, really important for patients and providers to understand, who is a good candidate for this therapy, who's a good candidate for focal therapy? So we split patients roughly into three buckets when we talk about prostate cancer: low, intermediate, and high-risk prostate cancer. And that mostly aligns with the Gleason score and a little bit with the PSA. So the Gleason score is a measure of the pathologic grading of the cancer, and it corresponds with the cancer's aggressiveness.

So patients in the intermediate risk category have either Gleason 3+4 or 4+3. Basically they have a Gleason 7 cancer. So those are the patients that we are considering for HIFU, for focal therapy with HIFU or focal therapy with IRE. In addition to that, they need to have an MRI-visible lesion. So we get an MRI, we can see where the cancer is. Where that MRI lesion is matches up with where the biopsy says the cancer is. So we can be very confident that that is exclusively where the cancer is. We can treat only that region. If there's cancer on both sides of the prostate, that's probably not a great patient to consider for focal therapy. If the cancer is invisible in MRI, that's certainly not a good candidate for focal therapy because if we don't know where the cancer is, then we, of course, can't treat it effectively with these options. Those patients are better served with a radical prostatectomy or radiation therapy because regardless where the cancer is, it's being treated.

Scott Redding:
So you mentioned about the MRI. How is that done? I've heard talk about like MRI fusion, a biopsy. Is it done via that or is it done just as a normal MRI to locate where that tumor is on the prostate?

Dr. Andrew Wood:
Yeah. So it's the same sort of MRI that we use for diagnosis of prostate cancer. So essentially, standard of care these days is to get an MRI before the biopsy, wasn't always the case, but now we get an MRI before the biopsy, which allows us to target any areas that are concerning on the MRI when we do the biopsy. So that MRI is the MRI that we use to determine where it appears the cancer is. And then the subsequent fusion biopsy tells us, is the cancer where the MRI thought it was? And if it is and it's in that intermediate risk category with Gleason 7, that's the kind of patient that we would consider for focal therapy.

Scott Redding:
You mentioned CyberKnife from a radiation standpoint, but then you've also mentioned early on about NanoKnife. What is the difference between those two and how is it utilized for the standpoint of prostate cancer?

Dr. Andrew Wood:
Yeah, great question. So interesting, because the names are so similar. So NanoKnife is the commercial name for a technology known as irreversible electroporation. So IRE for short. And what that is, is effectively we surround the cancer with electrodes and we pass electrical current between the electrodes. A sufficient level of current will induce pores in the cell membrane. That's where you get the electroporation. And if the pores are large enough, the cell can't repair them and all those cells will eventually die and be reabsorbed by the body. This is a newer technology still used for focal therapy ablation. It was invented somewhere in the early 2000s, 2005 to 2010.

Its advantages over some of the older therapies like HIFU and cryo is that it doesn't generate any heat at all. There's no heat changes. So there's not heating like with HIFU, there's not cold as in cryotherapy. So the damage to local tissue around is substantially less. The electricity doesn't affect the surrounding structures even to the level of cryotherapy and HIFU, which already in and of themselves are minimally invasive therapies. So it is also used primarily for patients with anterior tumors. And the data is, a little bit early to say this definitively, but we think that probably patients have less side effects from IRE than they do from cryo, which in and of itself, focal therapy with cryo has less side effects than something like a radical prostatectomy or radiation. Also importantly, because it has less effect on the surrounding structures, we think it probably makes it easier to do a surgery afterwards if we need to. And the data's very early on that, that's not definitive, but that's one of the possible benefits of NanoKnife IRE.

Scott Redding:
So we've hit on talking about side effects. We've not actually discussed what those side effects are. So what are the side effects with either surgery, radiation, and then with the focal? What are the differences between those side effects?

Dr. Andrew Wood:
Yeah, absolutely. Great question. So there are, of course, side effects with any therapy. When we're talking about surgery and radiation, which are, again, therapies that treat the entire prostate, there are two primary long-term side effects that affect patient's quality of life the most. Those being erectile dysfunction and urinary incontinence or loss of control of the urinary stream. Erectile dysfunction is something that affects potentially up to half of men after both surgery or radiation. It's common enough that here at the University of Michigan we have a standardized pathway to support patients who may have erectile dysfunction after radical prostatectomy. We offer them visits with sexual therapists at six to eight weeks after surgery as well as PDE5 inhibitors like Cialis shortly after surgery to help with the potential for those side effects. In terms of urinary incontinence, that is also a potential side effect after both surgery and radiation. And because of that, patients after surgery also get a referral to pelvic floor physical therapy to allow them to have a more speedy recovery from the possibility of urinary incontinence.

So that's sort of the expectations of those two side effects for radiation and surgery. In terms of focal therapy, we see improvements in both of those domains. So whereas potentially up to half of men will get erectile dysfunction after surgery, only about 10% of men after focal ablation with HIFU, cryo, or IRE will have that same issue. In terms of urinary incontinence, those numbers are a bit lower after surgery and radiation, but virtually non-existent. Zero to 1% of men will have any issues with lack of urinary control after focal therapy with any of the mentioned options. So it really is a tremendous benefit to patients, and studies have demonstrated significant differences in quality of life, health-related quality of life, after focal therapy.

Scott Redding:
If we go back a little bit about the appropriate patients and being in that intermediate Gleason score area, where does that fall under from if someone's hearing a staging like early stage, stage 3+, or advanced stage cancer, where would that fall in for those patients?

Dr. Andrew Wood:
Yeah, that's a great question. We get that question all the time in terms of, what stage am I? The staging system for prostate cancer, really the most important differentiator that you need to be aware of is, is your cancer localized to the prostate or is there any evidence that it's spread beyond the prostate? Okay? So for the risk stratification system, we talked about low, intermediate, and high-risk. Those are talking about patients with localized prostate cancer, meaning we don't have any evidence that the cancer is spread outside the prostate.

How do we determine that? We use PSA, of course. So if your PSA is very high, we worry that it may have spread outside the prostate. The MRI will also look at the lymph nodes, and so it will see if there's any very obviously enlarged lymph nodes. And then in certain patients, we'll get something called a PSMA PET scan, which is a modern cutting-edge PET scan specific to prostate cancer that allows us to very accurately determine whether a cancer is spread outside the prostate. So in order to even have a discussion about focal therapy, we would have to have a good confidence that your cancer is localized to the prostate.

Scott Redding:
You talked about localized cancer and this all falling underneath that. Can you tell us a little bit more about what patients in general can expect here at Michigan with localized cancer and from a standpoint of overall patient care?

Dr. Andrew Wood:
Men that come to us here at the University of Michigan with a diagnosis of prostate cancer are taken care of in a multidisciplinary way as a part of the Weiser Center for Prostate Cancer, which is a collaborative group among urologists, radiation oncologists, and medical oncologists that allow patients to get the best possible care. We have a multidisciplinary clinic that allows patients to see both radiation oncology and urology at the same time so that they can hear about both surgery and radiation, and even some of these focal therapy options all at the same time, and hear about the risks and benefits of each.

Scott Redding:
Is there anything that I've not covered that you want to make sure that we've covered here?

Dr. Andrew Wood:
What's really, really important is to understand, we did already cover it, but I just want to reiterate it, who is a candidate for this and the importance of getting a high-quality MRI and a high-quality MRI-guided fusion biopsy upfront. In order to be considered for any of these therapies, those are absolutely mandatory. The other thing that I wanted to mention that's really important, that we hit on a little bit, but it's important for patients to understand, is the surveillance schedule. So because we're treating only part of the prostate, we got to pay attention to the rest of the prostate and also make sure that there's no recurrence in the area that we treated. So how we do that is we do regular PSAs. We do about a PSA every three months for a year, and then we go to every six months. We do an MRI at six months and at 12 months, and then we go to yearly MRIs. And then we do one scheduled biopsy one year after the procedure.

So that is just to make sure that we're not seeing any evidence of recurrence. We know that if we're going to see a recurrence, it's usually going to happen in the first one or two years. So after that, we tend to back off on the surveillance schedule a little bit. But it's important for patients to realize both that if you elect for focal therapy, there's a little bit of homework to do afterwards. But it's also, I think, really reassuring to know that we are going to follow you through the time afterwards. We're going to make sure that if there is something that comes back, we catch it, we take care of it.

Scott Redding:
Great. One last thing real quickly is, as we wrap up, when it comes to talking about focal therapy, and we've talked about the three and how they've progressed over time to different, what's the future with focal therapy? Are there clinical trials around newer or additional opportunities?

Dr. Andrew Wood:
Yeah, great question. So first and foremost, there are ongoing clinical trials in each of these spaces in order to longitudinally follow patients so that we can get sufficient data, 10, 15, 20-year follow-up data, so that this can become considered eventually, in my opinion, a standard of care. Right now it's very new, but we need to have that 10, 15, and 20-year follow-up to be able to say this can be considered a standard of care for treatment of prostate cancer to provide its benefits to all patients.

The other place where I see a tremendous improvement over the course of the next 10 years is prostate MRI. We didn't mention this, but 15 to 20% of clinically significant prostate cancer is invisible on prostate MRI. So that's 15 to 20% of patients, if they have a prostate cancer, who won't be eligible for focal therapy. But prostate MRI now, compared to five years ago, is tremendously improved. And I see that continuing to improve over time with improvements in quality, improvements in radiology interpretation, improvements in urologists' understanding of prostate MRI and comfort with it. And then even more exciting is the applications of AI, artificial intelligence, on prostate MRI interpretation and detection. There's already exist AI systems that can help radiologists to find prostate cancers, and I expect that to continue to evolve. Anything having to do with improvement in prostate MRI is going to make a huge difference in our ability to effectively deliver focal therapy options.

Scott Redding:
Well, Andrew, I really appreciate the time. Thank you again.

Dr. Andrew Wood:
Yeah, thanks so much for having me. It's been a blast.

Scott Redding:
Thank you for listening. Tell us what you think of this podcast by rating and reviewing us. To stay up to date on what's happening in the cancer world, follow us on X at @UMRogelCancer. You can explore additional episodes at www.rogelcancercenter.org/podcasts.

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