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Eric Klein, MD, Urologic oncologist and Chairman Emeritus of the Glickman Urological & Kidney Institute joins the Cancer Advances podcast to discuss how we are leading the way in prostate cancer care. Listen as Dr. Klein highlights the four areas of innovation that are transforming the treatment of prostate cancer and providing individualized, high-quality care for our patients.

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Leading the Way | Innovations in Prostate Cancer Care

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 again by Dr. Eric Klein. Dr. Klein is a Urologic oncologist and Chairman Emeritus of the Glickman Urological & Kidney Institute. He's here today to talk to us about innovations in prostate cancer care at Cleveland Clinic. So welcome, Eric.

Eric Klein, MD: Thanks, Dale, great to be here.

Dale Shepard, MD, PhD: So you've been with us for a couple of other episodes, but maybe we can start out and just remind us your role here at Cleveland Clinic?

Eric Klein, MD: I am the chairman emeritus of the Glickman Urological & Kidney Institute, and a practicing urologist whose practice is devoted to the management of prostate cancer.

Dale Shepard, MD, PhD: Well, we're going to be talking about prostate cancer today. So maybe let's start in a very broad way, and maybe you can tell us about some of the exciting and innovative things that we're doing for patients with prostate cancer?

Eric Klein, MD: Sure. There are four general buckets of innovations that we've been working on the last several years that have really come to fruition in the recent past. One is smarter screening with a better blood test than PSA. Another is a better way of doing biopsies. The third is more effective monitoring for patients who choose active surveillance. Then the fourth is a number of innovative ways of treating prostate cancer if you have one that needs to be treated.

Dale Shepard, MD, PhD: All right, so let's take each of these. Tell me about screening.

Eric Klein, MD: Screening is an established method for finding prostate cancer. Most prostate cancer is found by PSA-based screening and there's recognition now I think, that most men starting at age 50, ought to get screened with PSA in an intelligent way. The challenge is the PSA is prostate specific, but it's not prostate cancer specific. So an elevated PSA is more often due to non-cancerous prostate enlargement, BPH, than it is to prostate cancer. So there's a need to refine our decision-making in terms of who needs to be biopsied because of an elevated PSA and who doesn't.

Dale Shepard, MD, PhD: Let's talk a little bit about that and how we make those decisions. I guess one thing that quickly comes to mind is there's a lot of confusion about screening and the role of screening and patients are confused, sometimes providers are confused. How do we make that better?

Eric Klein, MD: Well, so there's solid data now from a big screening trial that was done in Europe and men who are screened, men between 55 and 69, the target group, men who are screened are 27% less likely to die of prostate cancer and importantly, 35% less likely than men who aren't screened to need palliative treatment for metastatic disease. The big US trial called the PLCO, which looked at this and was negative, was flawed because most of the men and the arm that weren't supposed to get PSAs actually got PSAs, so it compared screening to screening. So there's solid data now. If you project it out to 25 years, the number needed to screen and the number of incidentally found low grade cancers are well within the parameters that we use for other established screening paradigms, colonoscopy, mammography, and so forth. So there's no question that screening is beneficial in my mind.

Dale Shepard, MD, PhD: So it seems as though those of us who treat the disease, of course know this, but when we get to the level of patients and their understanding of it, are there educational opportunities here? And if so, what would work best do you think?

Eric Klein, MD: Okay, well, it's to review in a way that consumers can understand the data that I just mentioned from the European screening trial and what the benefits are. We have to be open about the fact that the treatment carries side effects and that leads to some of the innovative things that we're doing. Maybe we should talk about the way we've been able to reduce the number of biopsies we do on men. So if you have an elevated PSA, the question is, do you have prostate cancer or not? PSA is not much better than a coin flip on that. So we've been working with a company called Cleveland Diagnostics to develop a different way of looking at PSA it's called IsoPSA, which is now commercially available. It's a way of measuring all the different PSA-related proteins in the blood that come from the disordered cancer cells and exploits the fact that normal cells make normal proteins, while cancer cells make abnormal proteins. So you can detect these abnormal proteins that are cancer-specific.

We did a big study of 800 patients in the Cleveland Clinic system and we found that when using IsoPSA, we can avoid biopsying about 50% of men who otherwise would have undergone biopsy because the IsoPSA test is far better at predicting whether or not someone has a cancer present that might need treatment. That's really exciting. I mean, that's going to have a huge impact going forward, where we can better interpret what a PSA might mean and only biopsy those men who are likely to have something that we want to know about.

Dale Shepard, MD, PhD: You say this is commercially available at this point?

Eric Klein, MD: It is now commercially available and there is an application in front of the FDA for approval. Last year, this technology got breakthrough designation by the FDA, which contractually obligates them to make a decision about it relatively quickly. So we hope by the third quarter that we will have a decision about whether or not this will be FDA approved.

Dale Shepard, MD, PhD: That's great. I know that for many years, you've mentioned that we really do need to look at the right patients to be treating here.

Eric Klein, MD: Yes.

Dale Shepard, MD, PhD: So once we've determined someone who's at risk, we use IsoPSA for instance, tell me about biopsies.

Eric Klein, MD: So, biopsy's gone through a sea change in the course of my career. Back when I was a resident, patients who were going to have a prostate biopsy were admitted to the hospital the night before they got Betadine showers and IV antibiotics, they went to the operating room and got put to sleep under general anesthesia, and we did finger-guided blind biopsies of the prostate, which were incredibly inaccurate. Many of the patients ended up staying an extra day in the hospital because of clot retention. So then came along transrectal ultrasound, which really revolutionized things and allowed us to do things more efficiently and more accurately. Then a few years ago came along MRI-guided biopsy with very sophisticated technology that allows us to identify areas that look worrisome in the prostate and do targeted biopsies. Those have generally been done trans-rectally, which is efficient, not the most comfortable thing for patients and has a finite risk of bacteremia and infection. In fact, there even have been some deaths reported to the transrectal biopsy from bacteremic sepsis.

So the latest move is toward trans-perineal biopsy, which basically uses the same technology, ultrasound and MR effusion, but where the needle is passed, not through the rectum, but through the skin and the perineum between the rectum and the testicles. What we've found is that's more accurate, particularly when using the MR and it also has almost no risk of infection, and we've been doing them under local anesthesia, sedation, and general anesthesia, depending upon the patient. Patients love it because there's really no discomfort associated with it. So that's another significant advance, and that will become, I think, the practice standard over the next few years.

Dale Shepard, MD, PhD: How widespread is it at this point?

Eric Klein, MD: In academic centers its being done, and I think in many community settings also, and it's growing. It does require a dedicated team, special expertise and some experience but I think the whole field will move this way, as I said, in the next few years.

Dale Shepard, MD, PhD: Here at the clinic are most patients getting biopsies by this?

Eric Klein, MD: Right now, it's about 40% and we're working on expanding. It requires some specialized equipment and we're working on acquiring that. In fact, we just got another new toy to play with, which is a micro ultrasound device, which is an ultrasound device that sees the internal architecture of the prostate better than standard transrectal ultrasound. So standard transrectal ultrasound probe is about nine megahertz. The micro ultrasound is 29 megahertz, almost three times as powerful. We have one or two publications in a comparative study showing it's as good as MRI in finding high-grade cancers. It's possible that this could really supplement MRI and in the future, it might be possible to have a prostate biopsy without needing an MRI, an accurate prostate biopsy without needing an MRI. So we're headed in that direction and that's going to take a few years to generate some more data, I think.

Dale Shepard, MD, PhD: Is our resolution good enough at this point? Or, or could you foresee that something like an IsoPSA leads you to higher risk patients, but then when you do imaging, you may or may not find something concerning? Or you think there'll always be a biopsy in play.

Eric Klein, MD: It's a great question. There's been this debate and great interest in determining whether a negative MRI would obviate the need for biopsy. The answer to that is probably not. The reason is that MRI does not see small, high-grade cancers. So if you look at really, Gleason's group three or higher, Gleason's four plus three or higher, if the tumors are less than a centimeter in diameter, MRI misses about 75% of them, micro ultrasound might be able to pick those up because it's different technology and it sees the tissue differently. That's an important thing that we need to decide on, but here's what I think the future screening paradigm ought to be. Let me say this, in the UK, if someone has a PSA above three, and they're in the target age range of 55 to 69, they get an MRI first, biopsy if there's an abnormality and no biopsy if there's no abnormality. That's one way to do it. In the US, most insurance companies are not paying for MRIs in patients who don't have a diagnosis of cancer, haven't been biopsied. So we need a different strategy.

What makes sense to me is screen with PSA. If the PSA raises an issue of the potential of cancer, do a reflex test like IsoPSA or OPKO 4K, or prostate health index. If that's negative, you probably don't need to pursue a biopsy. If it's positive, then do an MRI because the test suggests that there's a cancer present. We know that MRI does make on average, a biopsy more accurate and better, even though it doesn't see everything. Then this is my view, biopsy everybody with a positive reflex test and elevated IsoPSA, for example. Even if the MRI's negative, because my hypothesis is the patients with an abnormal IsoPSA, or OPKO 4K, or prostate health index and a negative MRI, are the ones that have high-grade cancers at the MRI misses. So that's what I think the screening paradigm ought to be. At some point we'll have to do a head-to-head study, comparing a blood-based biomarker versus an MRI, in deciding on initial biopsy.

Dale Shepard, MD, PhD: How about monitoring? You said there's some exciting innovations in monitoring?

Eric Klein, MD: Yeah. So many years ago, working with several companies, decipher and what was then called Genomic Health, we helped develop some gene expression profiles on prostate biopsies that predict molecular aggressiveness that's not apparent to a pathologist looking at white light histology, and we just published 20 year outcomes from the original archetype cohort of about 500 patients here. It's remarkable if you have a low score with oncotype on a piece of prostate, your risk of getting metastatic disease or dying is really small at 20 years, 1% or 2%. If your score is above 30, then the risk of metastasis or death is measurable. Again, most patients with prostate cancer don't die of their disease, so the highest risk is on the order of 10% or 15%.

Nonetheless, this data 20 years give us confidence that if you have a high score on one of these tests, you shouldn't ignore it. That's a real cancer that needs treatment. If you have a low score, you're probably a good candidate for surveillance and need to continue to be monitored. But again, if you have a high score, there are three things you could do. You could look a little harder and prove whether or not a high score that was seen on a low-grade biopsy might actually indicate higher grade cancer that's present. You might look a little harder or be monitored a little closer, or I think you could make the argument to treat that patient. It's just amazing to me that an accurate prediction of your likelihood of metastatic disease or dying of prostate cancer can be obtained from one millimeter of prostate tumor on a biopsy. That's really remarkable.

Dale Shepard, MD, PhD: That's pretty impressive. Now, how did those profiles vary from an age-specific standpoint? Because oftentimes the younger patients that we see tend to have a little bit more aggressive disease.

Eric Klein, MD: Yeah, so I don't think that we've ever looked at age. In the models, age is not a predictor. I don't think that that's a real consideration. We also have data that shows that these tests perform well in both Caucasians and African-Americans. So they're usable all across multiple different patients.

Dale Shepard, MD, PhD: When we think about monitoring, what role have changes in imaging affected your practice?

Eric Klein, MD: Yeah. So MRI is important also in monitoring patients on surveillance. In general, we would recommend them every year or so. We make a decision on re-biopsy to determine if the cancer has become more aggressive based on the MRI. What we have learned though, is what I mentioned earlier, is that even if the MRI hasn't changed over the course of two or three years, and they often don't, that doesn't mean you can avoid doing a biopsy. Biopsy's still the best way to know what's going on inside the prostate and whether or not the tumor has reached a point where it needs to be treated.

Dale Shepard, MD, PhD: How about imaging, like fluciclovine or PSMA?

Eric Klein, MD: So those kinds of PET scans are going to revolutionize what we do in prostate cancer. Actually, the scientist who cloned PSMA is actually here at the Cleveland Clinic, Skip Heston, he cloned it way back when, when I was a fellow in oncology at Sloan Kettering. I don't want to tell you how long ago that was, but it's been around a long time. These are very revealing because they see things that standard imaging cannot see. So it gives you a real example from a study that we participated in recently with a company called Bluer PSMA-based imaging and men with PSA recurrence after either radiation or surgery. So I had a patient that I did, who was a candidate for prostatectomy. He had high-grade cancer, but conventional imaging, CT scan, bone scan were negative, did not suggest anything outside the prostate. So we did his prostatectomy and if all the cancer's, removed PSA ought to go to zero and it didn't in him, it went to some low level like 0.4, 0.5, something like that.

So we repeated in his conventional imaging studies, nothing seen on CT scan, nothing seen on bone scan. So he participated in this study where we did a PSMA scan and it turned out he had a solitary rib lesion, that even in retrospect, was not seen on any of the studies and we had to do an MRI to confirm. So he got radiated and his PSA went right back down to normal. So it's really remarkable. This PSMA is FDA approved now, but not available any place except on the West Coast. We're working on getting it here and I hope by the end of the year, that we'll be able to offer this for patients prior to surgery or radiation, if they have high risk features and are at risk for metastasis, and certainly in patients who have a rising PSA after definitive treatment.

Dale Shepard, MD, PhD: Innovative treatments, what can you tell me about what we're doing here at the clinic with innovative treatments?

Eric Klein, MD: So lots of interesting things going on there, the most interesting thing that we have now is a device called Focal One, which allows us to deliver energy in the form of high intensity focused ultrasound, think of it like laser light. Light from a light bulb is the same as light in a laser, it's just in a laser, it's all one wavelength. So ultrasound that's unfocused is harmless and doesn't damage tissue, but when you focus it, you can actually kill tissue with it. So this is a device that allows us to put the patient asleep in the operating room, put the probe in the rectum and use MRI and our biopsy guidance to identify a portion of the prostate where the tumor is, and to destroy the tissue where the tumor is and a small margin around it. It's outpatient treatment.

It requires a catheter for a few days, but after that, patients go right back to normal activities and they don't have the same risk of side effects of urinary problems, or erectile dysfunction, or bowel problems that come with radiation or surgery. It looks very promising. There really isn't any long-term data on this. It certainly seems doable and it's very attractive to patients because of the lack of side effects, but it's only for a certain subset of patients. They have to have one spot on an MRI and the biopsy has to show that it's a cancer that needs to be treated because of its biology or of its gene expression profile. It has to be located in an area that's reachable by the probe, so my estimate is about 10% to 15% of patients that we see are going to be eligible for this but it's an interesting advance.

Dale Shepard, MD, PhD: Tell me about single-port robotic surgery.

Eric Klein, MD: Yeah. This is a real advance that one of my colleagues, Dr. Koauk, has really pioneered. Robotics has been around for about 20 years now and in my estimation, the results between robotic and open prostatectomy have been very similar until recently. The advent of the single port and some innovative thinking by Dr. Koauk and others has allowed very safe prostatectomy and many patients, not all, go home the same day. The average length of stay in the selected patients is about four hours after surgery, which is really remarkable. Not that standard prostatectomy has a long length of stay, it's really just overnight, it's just one night in the hospital typically, but it's pretty clear that the system trauma to having it done this way is lesser and patients can safely go home there. So, that's really remarkable. Again, not everybody is a candidate for that either, but a substantial portion of patients are and that's going to revolutionize what we do.

In fact, CMS now considers radical prostatectomy an outpatient procedure, which is remarkable because again, when I started my career, the hospital stay was nine days. It was one day pre-op, the day of surgery, and then everybody stayed for seven days. So it's amazing what progress we've made.

Dale Shepard, MD, PhD: That's crazy. Then not only a decreased length of stay, but also other things like decreased need for narcotics and things like that as well, right?

Eric Klein, MD: Definitely less painful and catheters are staying in for three or four days instead of a week, and urinary control returns pretty quickly. I mean, quicker than usual. So, this is going to be the new standard, I think as the word gets out and people learn how to do it.

Dale Shepard, MD, PhD: Other innovations?

Eric Klein, MD: Yeah, there's another interesting idea that we're toying with, two things actually. In the form of focal therapy, like the Focal One, where we just treat one focus in the prostate, we're going to be opening a clinical trial soon called AuroLase, A-U-R-O-L-A-S-E. This involves infusion a day before a treatment of gold nanoparticles that are smaller than red blood cells, that leak into tumor beds because the capillaries in the tumors are leaky. Then we take the patient to the operating room and again, using the same kind of targeting, using MR, we can put a laser fiber into the prostate and heat up the gold particles, and that destroys the tissue.

That's another way of doing focal therapy and the potential advantages, as I mentioned, with the Focal One device, there are some constraints in terms of the locations of the tumor and the size of the prostate we can treat because it's done transrectally and if the tumor is too far away from the rectum, then it won't reach it. On the other hand, with this interstitial laser treatment, it doesn't matter how big the prostate is and it doesn't matter where the tumor is, we can hit it. So that's one additional advantage.

Then the last thing is something that's a little more controversial, but it's interesting and we're working on trying to sort out whether or not this makes sense. I call it surgical focal therapy, which is using the single-port robot to remove surgically, just a portion of the prostate, just a quadrant of the prostate that contains the tumor. The potential advantage there is better functional results and particularly preservation of erections. That's the big bugaboo with radical prostatectomy, is preservation of erections. Patients do pretty well as far as urinary control goes, no matter how the prostatectomy is done, but recovery from erections is variable and takes a long time. It takes 24 months and only about 70% to 80% of patients who have a good nerve-sparing operation recover their erection. So this kind of surgical therapy has the advantages of surgery, of removing the tissue and getting a pathology report and so forth, and may have the advantage of better preservation of erections. Again, it's not for everybody, we're being very selective about the patients that we're doing it in, but it's an interesting concept. It just adds to all of the innovative things that we've been thinking about.

Dale Shepard, MD, PhD: Well, looks like there's certainly a lot of innovation. There's a lot of creative things going on here at the clinic. We appreciate your insight. Is there anything in addition you'd like to add?

Eric Klein, MD: Just to get patients to think about these things and ask their urologist about them and try and think outside the box a little bit.

Dale Shepard, MD, PhD: Very good. If you were interested in more information about the IsoPSA test, you can find an additional podcast episode with Dr. Klein on our website, So thanks a lot for being with us, Eric.

Eric Klein, MD: A pleasure, thank you, Dale.

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


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