Smarter Screening, Better Biopsies, and Breakthrough Treatments for Prostate Cancer

Podcast Transcript

Dr. Scott Steele: Butts & Guts, a Cleveland Clinic podcast exploring your digestive and surgical health from end to end.

Hi everybody and welcome to another episode of Butts & Guts. I'm your host, Scott Steele, the Chair of Colorectal Surgery here at the Cleveland Clinic in beautiful Cleveland, Ohio. I'm so pleased to have maybe a little bit of a trip for Butts & Guts, going to step out of the digestive disease world and step into the world of prostate cancer. I'm so pleased to have Dr. Eric Klein, urologist oncologist. Dr. Klein, thanks so much for joining us here on Butts & Guts.

Dr. Eric Klein: Thanks, great to be here.

Dr. Scott Steele: We're going to talk a little bit about screening and biopsies and treatments for prostate cancer. But before we jump into that, as all of the listeners know out there, I always like to start out with you telling the audience a little bit about yourself. Where are you from? Where did you train? And how did it come to the point that you're here at the Cleveland Clinic?

Dr. Eric Klein: How much time do we have? That's a long, long history. I grew up in suburban Philadelphia. I went to Johns Hopkins as an undergrad, University of Pittsburgh and medical school where I met my wife and we came to Cleveland to do our training in the early eighties. We went to New York for fellowship in the late eighties, and we've been back in Cleveland since 1989. I've been in the Department of Urology and what eventually became the Glickman Institute all that time, 32 years now.

Dr. Scott Steele: That's fantastic, and we're sure glad you're here. For all the listeners, just to remember that September is actually prostate cancer awareness month. And prostate cancer, as many of you know out there, is very common. Affects one out of every nine men. Cleveland Clinic, I'm proud to say, is at the forefront of transforming the treatment of prostate cancer and providing individuals with high quality personalized care for our patients. That's what we're going to delve into a little bit with Dr. Klein about this today, so let's go high level first. What is prostate cancer and how does it come about? How's it caused?

Dr. Eric Klein: Well, prostate cancer is obviously what it says, it's a tumor or a cancer in the prostate. Although it's a little different than other organs, because it's usually microscopic, it doesn't form little lumps of tumors, generally. What causes prostate cancer, generally we don't know the answer to that. Having said that, some of it is due to genes that are inherited, that increase the risk of getting cancer and probably the best known one is BRCA. Men who have BRCA1 and BRCA2 mutations are three to five times higher risk of getting a prostate cancer. And those with BRCA2 mutations have the most aggressive kind of prostate cancer, but those are pretty rare. So in general, most prostate cancer's what we call sporadic, it just happens, probably due to environmental exposures, maybe dietary exposures and interactions with a patient's genetic makeup. But that's about all we know about it currently.

Dr. Scott Steele: I heard once that... I gave the statistic one out of every nine men, but I heard once somebody said, "Listen, if you're a man and you live long enough, you're going to get prostate cancer." Is that true?

Dr. Eric Klein: Yeah, it is true, actually. If you look at autopsy series, most men in their late seventies, eighties, nineties have some prostate cancer. So one of the challenges is that we know that those cancers are often there for decades and they never become clinically evident. So it sort of leads me into the current screening paradigm, using the blood test PSA, which is prostate specific, but not prostate cancer specific, so there are two problems with it.

One is that most men who have an elevated PSA don't have prostate cancer, they have non-cancerous prostate enlargement. And as we get older, the prostate gets bigger and makes more PSA and our cells get leakier and more leaks into the system, so a lot of false positives. The other problem is really related to that, is that we over detect a lot of... Or we have in the past, we over detect a lot of low grade cancer that appears in older men in autopsies. But if we find it in a 50 or 60 year old, we used to think we had to treat them all and we have learned that that's no longer the case.

Dr. Scott Steele: Let's just rewind real quick and just make sure that I understand. What is a PSA test or an IsoPSA test? Is one of these more sensitive than the other? When would you necessarily get one of these types of two tests?

Dr. Eric Klein: PSA is a protein that's made by prostate cells, benign or malignant. There's more PSA in the bloodstream if you have cancer, generally. It's tested just through a simple blood test, and in fact, standard screening guidelines are that men between the ages of 50 and 69 should be screened once a year for prostate cancer, using a PSA blood test. That has been shown in randomized trial, which is the highest level of scientific evidence that we have, comparing screened men with PSA to non-screened men. If you were screened, you were 27% less likely to die of prostate cancer and 35% less likely to need palliative treatment for metastatic cancer, so PSA saves lives.

Just thinking about it as one of the standard screening tests as there are for others. So colonoscopy and Cologuard for colon cancer, mammography for breast cancer, pap smears for cervical cancer, low dose CT scans for high-risk smokers and industrial exposure for lung cancer, so it's in that category. Again, getting back to what I said before, the limitation of PSA is prostate specific. So it can tell us that there's disease in the prostate, but it's not prostate cancer specific, so it's not much better than a coin flip in deciding whether someone has BPH or prostate cancer. There have been some other tests on the market, similar to IsoPSA in concept, that are more sensitive and specific for finding a cancer that we would want to treat.

So my current paradigm, and I'm trying to convince the world of this, is that if you have a worrisome PSA that's elevated, that the next thing to do is an IsoPSA test. Because if you have an IsoPSA test below six, you have a 92% chance of not having a high grade prostate cancer, which are really excellent odds, and you probably don't need a prostate biopsy. If the IsoPSA cutoff is greater than six, you have at least a 50% chance of having a high grade cancer and you should have a biopsy. We have data now in several thousand men showing that when it's used that way, we avoid doing prostate biopsies in about 55% of men who used to get a biopsy, and that's a real boon.

Dr. Scott Steele: It wasn't too long ago that I recall though, but they were some... And I don't know if it's delayed press or if it actually gained traction, but people were saying that you shouldn't get a PSA, and you should be able to go away. What was that all about and where do we stand with that right now?

Dr. Eric Klein: Yeah, that was about something that I won't characterize, but I would like to, as misinformation. There's a government task force called the U.S. Preventive Services Task Force that makes recommendations to Medicare on what to cover in terms of screening tests. They looked at all the data back in 2012 and came out with a recommendation against screening. What they said, there might be that one out of the thousand men who have a PSA test might have their life saved by having had the PSA test, but that there were a lot of harms that occurred to men who didn't need life-saving surgery. Those harms were the discomfort and the complications of a prostate biopsy, and then over treatment of low grade cancers that PSA found. So people then said, and many of the primary care societies said, "We're going to follow this task force recommendations and stop screening."

What we learned over the ensuing seven years is that the rate of men presenting with metastatic prostate cancer and with locally advanced prostate cancer, which is much harder to treat, went up when screening went down. So I think there's pretty clear consensus now that screening the appropriate age group save lives and reduces metastatic cancer. The task force reversed its recommendation in 2019, I think it was, and said that at least men in that age group, 55 to 69 ought to talk to their physicians about the pros and cons of screening. But they recognize that we biopsy less frequently now and they also recognize that the urologic community has established something called active surveillance. So a man with a low grade tumor who 20 years ago would, without question gotten treatment, now is managed by surveillance or observation and we don't treat those patients unless the cancer progresses.

Dr. Scott Steele: So with regular listeners to this podcast, I like to play a little segment that's called truth or myth. You spoke to maybe the specificity or sensitivity or PSA on the high side, but truth or myth, a low PSA means you do not have prostate cancer?

Dr. Eric Klein: That's generally true, but it is possible to have a high grade aggressive prostate cancer that does not make much PSA, so there's really no PSA below which the risk of prostate cancer is zero. Having said that, if you're in your fifties or sixties and your PSA is below two and a half, it's really unlikely that you have prostate cancer.

Dr. Scott Steele: Talk to me a little bit more about prostate cancer itself. Is there only one type of prostate cancer? And if I'm listening to this episode out there, I'm about to be 50, now what type of symptoms am I looking for, for the potential for having prostate cancer, versus this asymptomatic screening that we were talking about earlier?

Dr. Eric Klein: The predominant form of prostate cancer, which accounts for 98% or 99% of all prostate cancers, is adenocarcinoma, that's typical prostate cancer. But there are some variants since there are some other cells in the prostate that sometimes can give rise to tumors, but they're very rare. Symptoms, the real challenge is that most prostate cancer is asymptomatic, so you can have symptoms that men get starting at age 50, urinary difficulties, getting up at night, slow stream, feeling like you don't empty, that are very, very typical of prostate enlargement, and that's what they come from. But you can have both prostate enlargement and prostate cancer, so in reality, most patients with localized prostate cancer have no symptoms and it's suspected only if they have a PSA.

Dr. Scott Steele: If you're talking about a biopsy, what does this mean? Why would somebody get a biopsy? How is it done? Are there different types of biopsies? And is one type better than another?

Dr. Eric Klein: Yeah, a biopsy involves putting a needle into the prostate and taking a piece of tissue and sending it to the pathologist to look at under the microscope. That's the only way you can actually diagnose prostate cancer, and we're in the middle of a shift in the way prostate biopsies are done. The most recent technology has been placing an ultrasound probe in the rectum, squirting some Novocaine around the prostate, and then doing random biopsies of the prostate using ultrasound as a guide. And they're random biopsies because ultrasound generally doesn't see prostate cancer.

The next leap in technology that came along probably seven years ago now, is MRI of the prostate done before the biopsy. That allowed us to identify areas in the prostate that look worrisome for high grade cancer, and have our radiologists mark those areas so that when we do the biopsy, we use the sophisticated what's called fusion technology, where we fuse the real time live ultrasound image with the marked MR and we can do targeted biopsies. That has been done, until recently, by passing the needle through the rectum. That's simple and reasonably well tolerated, although there is some discomfort with it. But it has some side effects, bleeding from the rectum, bleeding from the urine, some blood in the semen and a measurable risk of bloodstream infection because the needle goes through the rectum.

So the current standard that we are shifting to now is called transperineal biopsy, where we still use the ultrasound in the rectum, and we still do the fusion with the MR, but the needle is passed through the skin, just in front of the rectum, rather than through the rectum itself. And that is more accurate, it's more comfortable for the patient and there's no risk of infection. I believe that that's the current standard of care and the way all prostate biopsies should be done, is in using the transperineal approach.

Dr. Scott Steele: So once you diagnose that somebody has prostate cancer, what are the types of run of the mill treatments or standard treatment for most common prostate cancer? And how do you decide on what type of treatment should be geared towards that individual patient?

Dr. Eric Klein: Yeah, that's a long discussion now because there are so many options, but very briefly for the lowest grade cancers, we manage those by active surveillance without treating them. That is the correct thing to do. We know that it's safe to do that, that men don't die of those cancers. Most men avoid any treatment at all during the course of their lives and they avoid all the side effects of treatment. If it's a cancer that needs to be treated, the standard approaches have been complete removal of the prostate, that's been called radical prostatectomy in the past, but probably a better term is total prostatectomy. And various forms of radiation therapy, external beam radiation, or something called brachytherapy, where we put radioactive seeds in the prostate, in a single treatment.

Then there are some new emerging treatments and the one that's popular is called focal therapy, where if someone has just a small tumor, let's say half an inch or so in one part of the prostate, that part of the prostate can be surgically removed, that's called surgical focal therapy or a partial prostatectomy. Or we can use different forms of energy, laser, or something called high intensity focused ultrasound, or cryotherapy to destroy just that part of the prostate. That's very new, we don't have long-term follow up yet, but it avoids more significant treatment-related side effects.

Focal therapy, the way we look at this is, again you have a prostate, think of it like a big citrus fruit, and there's a tumor just in one spot and the rest of the prostate doesn't have cancer in it. So rather than treat the whole prostate, which is the way we used to do it, and run the risk of difficulty with erections and urinary incontinence if you have surgery, or rectal issues because you get radiation, the Focal One device allows us, under anesthesia, to put a probe in the rectum to use the MR to target and outline exactly where the tumor is and surrounding normal tissue. And then use this high intensity focused ultrasound just to, what we call ablate or destroy that particular part of the prostate. Many, many fewer side effects, outpatient procedure, rapid recovery, and we're just evaluating now how well that works and who are the best candidates for that.

Dr. Scott Steele: You mentioned surgery in the past and talk about open versus robotic laparoscopies. Now, what role does minimally invasive and robotic surgery play for prostatectomy?

Dr. Eric Klein: Yeah, minimally invasive robotic surgery is the standard now. The robot came along about 21 years ago now, and the first robotic prostatectomy was described. At the beginning, the results were really not good as people were on their learning curve, and so I trained as an open surgeon and as we got the robot and people were getting better at it, I said to the team, "Prove to me that you can do a robotic prostatectomy better than I can, and then I'll learn how to do it."

About 10 years went by and the experience certainly got better, so we did a head-to-head study in-house here, of important outcomes for open versus robotic prostatectomy. We looked at length of stay in the hospital and pain and complications, and return of urinary control and preservation of erections, and we found no difference between the two. So I've continued to do open prostatectomy and we've got great people who have trained in the more recent past, who do robotic prostatectomy, and in my view, the results are the same. It's really about the experience of the surgeon and where they cut, and more importantly for prostatectomy, where they don't cut.

Dr. Scott Steele: I know that a lot of cancers, and I'm sure prostate is no different, their ultimate outcome depends on the stage or the aggressiveness of the tumor or anything, but do people still die of prostate cancer? I know there's some famous people out there that I've read about that have unfortunately passed away, but what is the long-term prognosis for that?

Dr. Eric Klein: Yeah, so the five-year survival rate for all stages of prostate cancer is a hundred percent. And the five-year survival rate for all stages of prostate cancer at 10 years is in the mid 90%. So the people who die of prostate cancer, are generally people who present with metastatic prostate cancer, where that's already pretty widespread. We have good treatments that slow down the growth of that cancer, but at present, I would say the vast, vast, vast majority of patients with metastatic prostate cancer are not curable. We use multiple different cycles of drugs to slow things down and those are the people who die. It's really unusual, if someone has a prostatectomy or radiation therapy for early stage disease, it's really unusual for them to die of metastatic cancer.

Dr. Scott Steele: What's on the horizon as far as additional research into prostate cancer, either screenings or the treatment?

Dr. Eric Klein: Oh, lots of wonderful things. I mean, we're working with one of our pathologists, Jesse McKenney, on a new way of grading prostate cancer so that we can more easily identify who has cancer that needs treatment, and who doesn't, and I think when that work is done, that's going to revolutionize things. We have been leaders in developing gene expression profiling or genomic testing, biopsies to determine who's a good candidate for surveillance and who needs treatment, and we just published 20 year outcome data on that. So that's very compelling, that in addition to MRI, these genomic tests ought to be used at the beginning to decide who needs treatment or not.

After the prostate's removed, we can do some genomic testing and we're getting to the point now where we can predict who's going to have a recurrent cancer and who isn't, and what kind of treatment we ought to give them to prevent that. So to predict who's going to respond to radiation and who isn't, and who might respond to chemotherapy and who doesn't. Then the real problem with more advanced stage disease is that men become resistant to the drugs that we use. So Nima Sharifi, who's in our Genitourinary Malignancies Research Center, just published a really important article that identified a new resistance mechanism for a commonly used drug called enzalutamide. He and his team, Shaun Stauffer, are working on new drugs that will attack that pathway so that patients can live longer.

So lots of new things. One last really new exciting thing is a molecule called PSMA, which was actually cloned many years ago by one of our scientists, who's retired now. And PSMA is the basis of a new kind of pet scan that was just approved by the FDA that will give us better, more accurate staging in men with prostate cancer. And this monoclonal antibody that targets PSMA can be hooked to a radioactivity molecule called lutetium, which can then hone directly to where the metastatic cancer is and has been shown to prolong survival. And might for the first time, at least in my lifetime, allow us to cure a subset of men who had metastatic prostate cancer. That's what I think's on the horizon, it's all pretty exciting.

Dr. Scott Steele: That's great stuff. We always like to end up with getting to know a little bit more about you with some quick hitters. So first of all, what's your favorite food?

Dr. Eric Klein: Anything that's cooked well, I'll put a plug in for a local restaurant called L'Albatros, which has a spectacular dish of cod. I have ordered it about 30 times in a row when I go there, it's really excellent. So I'd say the cod at L'Albatros is my favorite food.

Dr. Scott Steele: And a very nice outdoor patio.

Dr. Eric Klein: Yes.

Dr. Scott Steele: What's your favorite sport?

Dr. Eric Klein: Boy, it's hard to pick one. I'm a big LeBron James fan, and so last year's NBA playoffs were really terrific, particularly during COVID, but I like baseball and football also.

Dr. Scott Steele: What is the last non-medical book that you've read?

Dr. Eric Klein: Yeah, that's easy. I'm reading a book called Pizza Girl, which is a novel about a young girl working in a pizza parlor and all the interesting people and personal challenges that she has. It's quite funny.

Dr. Scott Steele: Fantastic, and then tell us something that you like... You've been here a while, tell us something that you like about either Northeast Ohio, or Cleveland in general.

Dr. Eric Klein: I think the thing I like most about Northeast Ohio is the fact that we're on the Western end of the Eastern time zone. And in the middle of the summer, it stays light till 10 o'clock at night, and that's really, really pleasant.

Dr. Scott Steele: That makes me laugh because I said that the one thing that I missed in the West Coast was to wake up and be able to watch NFL football and know that it was going to end and it was 4:30 in the afternoon. So that's fantastic that you brought that up.

Dr. Eric Klein: Yeah, I can see that.

Dr. Scott Steele: Tell us a final take home message about prostate cancer for our listeners.

Dr. Eric Klein: The most important thing is that when prostate cancer is caught early, it's easy to cure and we have far better ways than in the past of identifying who needs to be cured, and that's really the main thing. So if you're diagnosed with prostate cancer, the first question you should ask your doctor is, "Does this need treatment or not?" That's very different than when I was in training, where we believed that every cancer that we diagnosed needed to be treated.

Dr. Scott Steele: So to learn more about Cleveland Clinic's advances in prostate cancer screening, more effective monitoring, better biopsies and breakthrough therapies, please visit clevelandclinic.org/prostatecancercare. That's clevelandclinic.org/prostatecancercare. You can also call Cleveland Clinic's cancer answer line at 866.223.8100, that's 866.223.8100. And finally, you've heard me say this before, please remember that in times like these, it's important for you and your family to continue to receive medical care. And rest assured here at the Cleveland Clinic, we're taking all the necessary precautions to sterilize our facilities and protect our patients and caregivers. Dr. Klein, thanks so much for joining us on Butts & Guts.

Dr. Eric Klein: Thanks for having me.

Dr. Scott Steele: That wraps things up here at Cleveland Clinic. Until next time, thanks for listening to Butts & Guts.