The Art of Active Surveillance 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 this podcast to talk about transperineal biopsy and advances in screening for prostate cancer. That episode is still available for you to listen to. He's here today to talk to us about active surveillance for patients with prostate cancer. Welcome back.

Zeyad Schwen, MD: Great to be back. And thanks for having me again.

Dale Shepard, MD, PhD: Sure. Maybe remind us of a little bit about what you do here at Cleveland Clinic.

Zeyad Schwen, MD: Yes. I'm a urologic oncologist, so I do primarily surgery and diagnosis. My practice is primarily prostate cancer, but I see other cancers, people with bladder cancer, kidney cancer, testis cancer, different types of urologic malignancies. I do a lot of robotic surgery for prostate cancer as well as other urologic cancers, as well as different types of diagnosis techniques. The one that I am very passionate about is the transperineally biopsy approach for diagnosis. I also do focal therapies in select men, for people with prostate cancer. But today we're talking about active surveillance, and that's another passion of mine, trying to find people who have low risk cancer and who would be better off watching the cancer.

Dale Shepard, MD, PhD: Excellent. Prostate Cancer Awareness Month has kind of kicked off. So a very, very important and timely topic. We're going to talk about active surveillance, like you said. What does that mean? Tell us. There's a lot of different people that might be listening in. What does active surveillance mean?

Zeyad Schwen, MD: That's a great question because there's a lot of different names swirling around about what this is. The purpose of active surveillance is to still have the ability to cure the cancer, so trying to avoid or delay treatment in men, but watching them closely enough so we don't miss the window of being able to cure the prostate cancer.

Active surveillance is really a story of PSA screening. Before PSA screening in the early '80s and before, when people were diagnosed with prostate cancer, it was a fatal diagnosis. We missed the window where we could cure the cancer because it has already metastasized to other parts of the body. And it's something that really was a very important discovery, to identify a blood test that can identify prostate cancer early.

But then, the pendulum swung the other way. We caught the cancer early, but in some men, we were diagnosing people with prostate cancer who would've died of natural causes because of how low risk and how common it is for men to develop and have prostate cancer just being there and found after the fact. So, a lot of men ended up getting overtreated. That means men who had low risk prostate cancer, that wasn't going to ever bother them in their lifetime, we were treating and overtreating these men with low-risk disease. And then we found that there's a subset of these men, when we diagnose them with prostate cancer, safely monitor and see if there's any signs that the cancer is turning into a more aggressive cancer that could be potentially life-threatening. But the good thing about prostate cancer is, it is slow moving and slow growing in most cases, and so we can safely monitor them and catch the prostate cancer before it has the chance to cause problems and spread.

Dale Shepard, MD, PhD: Excellent. To sort of think back to an older term, to differentiate the approach, there used to be this concept of watchful waiting. How does watchful waiting differ from active surveillance?

Zeyad Schwen, MD: And this is the important differentiation from active surveillance. Watchful waiting is really waiting for symptoms from metastatic prostate cancer to arise. So watchful waiting isn't really for the purpose of curing the cancer, it's mainly for palliative reasons. People most of the time don't have symptoms when they have prostate cancer. It only starts to cause symptoms usually when it spreads to bones causing bone pain or spreads to other organs. That's when the cancer becomes metastatic. So watchful waiting is primarily reserved for men who are older, who have a lot of other medical comorbidities, that may die of just natural causes and not prostate cancer. So, we don't have to be as aggressive in monitoring. Really, it's just delaying intervention until people develop symptoms and then just trying to put the prostate cancer in remission rather than cure it.

Dale Shepard, MD, PhD: You mentioned that active surveillance keeps us from being able to treat people why they may not need treatment, this whole concept of overtreatment. A lot of our therapies for prostate cancer have moved much, much, much earlier into the stage of prostate cancer. Oftentimes patients would show up and say, "Well, if I have any cancer in me, I want it gone three weeks ago." And so, what were some of the risks? When you say overtreatment, what are the harms? What does overtreatment mean?

Zeyad Schwen, MD: Yeah, very good question. Cancer treatment has side effects and that really can negatively impact a patient's quality of life. So, we don't just think about cancer in terms of if you have cancer, we do everything we can to get it out. We also want to think about what's your quality of life is going to be after those treatments. And prostate cancer treatment, whether it's surgery or radiation or other treatments, they have side effects primarily from how it affects your urine control and other urinary side effects, but also how it affects your sexual function. And people have a really negative quality of life in some instances.

We just want to make sure that if we're going to expose you to those side effects, that it's for a reason that it's a more aggressive cancer rather than a cancer that was going to never bother you in your lifetime. That's where there's a delicate balance of trying to select men who have lower risk cancers that are safe to delay or not do any treatment for but monitor them closely enough that we can still catch the cancer before it has a chance to cause problems. Limiting and reducing the side effects and improving quality of life, that's what active surveillance is for.

Dale Shepard, MD, PhD: Makes sense. Patient shows up in your clinic, they say, "Look, my primary care, someone, told me I have prostate cancer." What are the things you look for to consider a candidate for active surveillance?

Zeyad Schwen, MD: Yeah, that's a great question. The primary thing that we look at is what type of prostate cancer we're dealing with. Is this low-risk prostate cancer or is it something higher, intermediate or high risk? A lot of people can hear these terms called the Gleason score. That's how the cancer appears under the microscope. Gleason six prostate cancer, there's another scoring system that they use called Grade Group. Grade 1 or Gleason 6 prostate cancer almost universally is a good candidate for active surveillance. Because we know that biologically Grade Group 1 and Gleason 6 prostate cancer doesn't have the ability to metastasize or spread outside of the prostate. So, these are obvious candidates for who would be a good active surveillance candidate.

There are some men who have low risk cancer on the biopsy, but otherwise have higher risk features that make us concerned that maybe there's more aggressive cancer being harbored in the prostate. Say your PSA is through the roof, or your MRI of your prostate looks very concerning for harboring more aggressive prostate cancer. So, we look at other tests. But in general, low risk cancer, no-brainer, active surveillance.

There are also some men who have intermediate risk cancer, what we call favorable intermediate risk cancer, and that's who meet a select subset of criteria that makes their intermediate risk cancer a little bit more like low-risk cancer. We can select some men with favorable intermediate risk prostate cancer who would be good candidates for surveillance.

And really, when you start people on surveillance, you don't just say, "Oh, we'll see you years from now." No, it's a regimen that's crafted to try to identify who might be harboring a more aggressive disease. And that way, we don't delay a necessary treatment if we need to.

Dale Shepard, MD, PhD: And that includes serial biopsies and things like that.

Zeyad Schwen, MD: Yeah. And that's actually how active surveillance has evolved. Over the years, it's changed. The initial surveillance cohorts that were done, one of them out of Johns Hopkins, that's where I trained. That was one of the first active surveillance programs. And the 15-year prostate cancer survival was 99%. It's incredibly high. So, in very carefully selected men, we can very safely watch prostate cancer.

But then we found out maybe we were being a little bit more restrictive. And also, these early programs did a lot of prostate biopsies and kind of turned people's prostates into pin cushions, if you know what I mean. They would essentially biopsy everybody once a year forever. And then we found out, not only are we maybe being a little too restrictive in our criteria, but our surveillance intensity is too much. So really, we've tried to deintensify active surveillance, so it's not going to be such a burden on patients. And also, so patients are compliant with active surveillance. No one's going to want to go to the urologist to get a prostate biopsy every year. There are risks associated with even biopsies, there's risks associated with doing other types of imaging. And from a quality-of-life standpoint, that's the other reason why we found ways to reduce the number of times we have to do a biopsy and try to do non-invasive management and diagnosis of people with prostate cancer.

Dale Shepard, MD, PhD: Certainly, most people with prostate really get fixated on their PSA. What role does PSA play?

Zeyad Schwen, MD: That's a good question. PSA is a great screening test, but it's also not very smart. It's a test that is good at selecting who might be harboring prostate cancer. But as far as watching surveillance, PSA is not the greatest test. We rely on other blood tests. One of them is called the Prostate Health Index, also the PSA density. These are ones that are a little bit better in people who have prostate cancer and are on surveillance.

If your PSA is shooting up consistently and you're on surveillance, that's obviously a warning sign. But we try not to look at one marker. We look at what a lot of the tests are telling us. What does your MRI look like? We get that every one to two years, to see if there's any changes in the prostate lesion if you have one. Is it growing? Are there new lesions? And then, if we are starting to see a pattern that this cancer may be progressing, we then consider a biopsy to try to diagnose a possible more aggressive cancer.

But PSA, not the greatest test. We have a few others. We also look at genomic testing where we take the tissue from the cancer and send it to some of these labs that look at high risk mutations in the cancer that could be associated with more aggressive biology. So not just the numbers of the PSA, but also, what is the biology of this cancer? Could there be a risk factor that could suggest it may want to progress? We look at a lot of different markers.

Dale Shepard, MD, PhD: In terms of markers, we had a previous episode, we talked to Dr. Klein about the IsoPSA test. Is that incorporated into this?

Zeyad Schwen, MD: Good question. IsoPSA is great primarily in the screening and initial diagnosis setting. It can help identify who may be harboring more aggressive, clinically significant prostate cancer. It still really has not been studied in the active surveillance population. So that's something that the IsoPSA may be a good selection for those who may be having prostate cancer, but not great at, or hasn't been studied yet in people who are being followed serially on surveillance.

That's kind of why I rely on other blood tests. The Prostate Health Index, that's one that has been studied in people who are on active surveillance and has been shown to predict prostate cancer progression in that population.

There's a lot of great tests. The PSA density, which is kind of the same PSA but measured as a proportion of the volume of your prostate. Bigger prostates make more PSA, and so finding a way to account for that with the PSA density is actually a very helpful test.

And we can use these blood tests and combine them with other markers like the MRI to find ways to reduce the biopsy frequency, who can avoid another surveillance biopsy. We try not to cause too much harm.

Dale Shepard, MD, PhD: You talked about MRI as an imaging modality. We have more sensitive measures now for metastatic disease like PSMA testing, things like that. How has that influenced providers looking for metastatic disease earlier, finding metastatic disease, starting people who may not have otherwise been known to have more advanced disease and gone into active surveillance? How has that impacted active surveillance?

Zeyad Schwen, MD: It's a great question. Really, it's a matter of finding better ways to select the right candidates. Because without the imaging part, whether it's an MRI or a PSMA PET scan, we were putting a lot of men who required treatment on surveillance. And then, we would eventually catch that, "Oh, maybe this is more aggressive prostate cancer." But the earlier that we can get them to the necessary treatment, the better. So, it's really disqualifying patients who otherwise wouldn't be good candidates and getting them to the right therapies.

MRI has really been the main imaging modality for men who are being considered for active surveillance. But if there's a warning sign, we sometimes consider a PSMA PET scan. Of course, it's primarily used for higher risk cancers, but it's starting to make its way into the lower risks, in more localized disease. For example, if we are having trouble finding a possible cancer, if we're worried. The PSA, maybe it's rising at a concerning rate and the MRI and our biopsies aren't showing anything, sometimes we'll consider a PSMA PET scan to try to localize a lesion in the prostate that may be a good candidate for a biopsy or a fusion biopsy.

Dale Shepard, MD, PhD: We talked previously about risks of treatment, advantages to active surveillance. I guess if you're truly actively surveilling someone, you're going to catch things that progress. What would other risks be? What are the risks of someone saying, I've got cancer, no doubt, you probably have patients that'll say, "Seriously, you want me to just watch this? I have cancer." What are the risks?

Zeyad Schwen, MD: This is a very common, common issue. And it's very understandable. The C-word, cancer, it's a very emotional word. It's usually associated with a life-threatening condition. And with prostate cancer, at least low risk prostate cancer, this is not what they're typically thinking about cancer. So, it's hard to get patients to understand that this is not a life-threatening disease at this state.

And that's why, actually, it has led to a little bit of a debate within our field about whether we even consider or call low risk prostate cancer or Gleason 6 or Grade Group 1 prostate cancer at all. Just the word cancer has led to a lot of men being immediately jumping into a treatment that they don't necessarily need. And that's where overtreatment, the belief is that there's a lot of people jumping into treatments just because of that term. It's good to know that that debate is going on within our field for patients. I just tell them, "Listen, right now we call this cancer. There are some who don't think it should even be called cancer." But at the same time, sometimes when people think that they don't have cancer, then they don't need to watch it. So that could lead to some men maybe not going on the proper surveillance.

So really, our job is education. Our job is to help patients and provide them with resources to help patients understand that this is not the same life-threatening condition that you hear about. This is something that is, in some ways, a bit of a nuisance. Now that we know about it, we have to watch it very closely. But at the same time, it is something that needs to be watched closely to make sure it's not progressing and making sure that you're not harboring a more aggressive cancer that could be potentially life-threatening. But it's our job to help patients and really educate them. Once that education and reassurance happens, then I think that most people are comfortable with staying and being on surveillance.

But it could be associated with a lot of anxiety and a lot of worry. And that, from a quality-of-life standpoint also, can negatively impact their overall wellbeing.

But we try not to let people jump into treatment unless they absolutely are adamant about it and not wanting to stay on surveillance. We try not to let that be the main reason why we do a treatment.

Dale Shepard, MD, PhD: Makes sense. When we think about education, of course it's educating patients and then there's educating ourselves. Do you think that, in general, as providers, active surveillance is used often enough? Is it used too often, and people get away and come in with late-stage disease, being dismissive as you said? Or do you think it's about right?

Zeyad Schwen, MD: We have a lot of work to do. The active surveillance rates are rising, which is good, meaning more providers are routinely considering patients with low-risk cancer as candidates for active surveillance. But the variation in practice is very variable. Meaning, some providers, and they've done studies on this, aren't doing enough active surveillance. And as a result, the United States as a country lags a little bit behind in uptake of active surveillance. But it's rising. It's something that we have work to do on the provider side in terms of the old type of thinking that, "Oh, this is cancer. All cancer needs to be treated." Or some men who are younger were previously considered not good candidates for active surveillance because, "Oh, they're young. They have many years ahead of them. We don't want to miss the window of a cure." However, that's been debunked. So, a lot of times, it's offering surveillance to the right population. Previously, similarly to younger men, African Americans were not being considered good candidates for active surveillance because they commonly harbor more aggressive prostate cancer. But that's been also debunked.

A lot of these things just need to make their way into our field as providers. And we need to do a better job of considering all comers candidates for active surveillance, but maybe tailoring surveillance to their age or their risk.

So, active surveillance needs to be utilized more. The other thing that's underutilized is watchful waiting. Watchful waiting, as we discussed, is really transitioning people to an understanding that, "Well, you're not going to die from prostate cancer. You're probably going to die from natural causes." So older men, men who may have been on active surveillance for many years, but as they get older, the chances that they're going to die from prostate cancer goes down, maybe they have more medical issues that are probably going to be the bigger threat to their life. And so, maybe the equation changes as people age and as people are diagnosed later in life. And finding ways to improve their quality of life and understanding that maybe we don't have to be ultra-aggressive in trying to diagnose more aggressive disease, maybe we just do a more palliative approach and identifying those who just might be good candidates for watchful waiting.

Dale Shepard, MD, PhD: Which are particularly important as we have more and more and more therapies available to patients once they develop metastatic disease.

Zeyad Schwen, MD: Yeah, absolutely. And that's where a lot of the revolution in prostate cancer management has been, has been in the late stage and metastatic prostate cancer. While those treatments, they do have side effects, they do have risks, overall, they're well tolerated and a good option for men who may start to develop symptoms from metastatic prostate cancer. But yeah, it's for men who are younger, who have a longer life expectancy. We usually say 10 years or longer as what's a good life expectancy for someone who would be a good candidate for active surveillance. Because prostate cancer is not going to kill you in 10 years. It usually is life-threatening after it has a chance to spread, become metastatic. And even beyond that, you have many years because prostate cancer is slower moving. So, if your life expectancy is under 10 years, maybe surveillance isn't the right option for you.

Dale Shepard, MD, PhD: It sounds like there's a lot of room for improvement in some areas, education, risk assessment. Are there any other gaps that would make active surveillance maybe more prevalent, more effective?

Zeyad Schwen, MD: Yeah. I think that truly the revolutions in artificial intelligence and in our ability to take into account many variables at once will really help us improve active surveillance, improve people who would be good candidates for active surveillance, but also identifying triggers to decide to do a biopsy as well as when to pursue treatment. I think active surveillance will help urologists and other medical providers take into account the many different variables at once to help make better decisions. That's something that we are working to develop here at the Cleveland Clinic. A lot of tools that could potentially be helpful in helping make decisions about active surveillance as well as other prostate cancer management. So, there's more to come on than in the field as a whole. I think we could really use these powerful tools to help us improve patients' outcomes.

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

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

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

This concludes this episode of Cancer Advances. You'll find additional podcast episodes on our website, clevelandclinic.org/canceradvancespodcast. Subscribe to the podcast on iTunes, Google Play, Spotify, SoundCloud, or wherever you listen to podcasts. And don't forget, you can access real time updates from Cleveland Clinic's Cancer Center experts on our Consult QD website, at consultqd.clevelandclinic.org/cancer.

Thank you for listening. Please join us again soon.