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Active Surveillance for Prostate Cancer: A Tailored Approach

Author Olivia Reid covers Active Surveillance for Prostate Cancer: A Tailored Approach on BackTable Urology

Olivia Reid • May 26, 2024 • 96 hits

When prostate cancer is at low risk of progression, active surveillance is often the preferred management approach to avoid treatment side effects. Urologic oncologists Dr. Aditya Bagrodia and Dr. Ashley Ross walk through the evolving landscape of active surveillance for prostate cancer as advancing technology allows for more efficient prostate cancer monitoring. Dr. Ross emphasizes the pivotal role of genomic testing, such as Decipher, in stratifying patients for surveillance based on their risk profiles. The integration of genomics, alongside traditional metrics like PSA density and MRI findings, allows for a more comprehensive understanding of disease biology and progression risk. However, the absence of rigid guidelines for active surveillance necessitates individualized risk assessment and shared decision-making between patients and clinicians.

This article features excerpts from the BackTable Urology Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable Urology Brief

•Germline testing reveals inherited predispositions to prostate cancer, while genomic testing assesses the current state and trajectory of the cancer.

•High-volume Gleason grade group 1 disease or biopsy interpretation uncertainties warrant consideration for genomic testing, as genomic testing aids in bridging discrepancies and enhancing diagnostic confidence.

•Extended-spectrum surveillance requires a cautious approach, especially for higher volume grade group 1 disease and younger patients. This necessitates shared decision-making and individualized risk assessment protocols.

•There is a need for more research on active surveillance in prostate cancer to help streamline management decisions.

Active Surveillance for Prostate Cancer: A Tailored Approach

Table of Contents

(1) Deciphering Genomics: Practical Applications in Prostate Cancer Surveillance

(2) Tailoring Surveillance Strategies in Prostate Cancer

Deciphering Genomics: Practical Applications in Prostate Cancer Surveillance

The integration of genomic and germline testing has become increasingly pivotal in prostate cancer management, specifically for patients with intermediate or low-risk disease and considerable life expectancy. The key difference between these tests is that germline testing reveals inherited predispositions, while genomics testing shows the current state and potential progression of the cancer.

Key considerations in prostate cancer surveillance include factors like disease biology and extent; metrics such as PSA density and MRI findings are utilized most frequently. Dr. Ross underscores the importance of tools like Decipher, a genomic test with validated prognostic capabilities, in stratifying patients for surveillance. Notably, high-risk genomic profiles correlate with heightened progression risks, guiding informed decision-making regarding surveillance duration and the necessity for confirmatory biopsies.

[Dr. Aditya Bagrodia]
There's nothing long-winded about it. It's fantastic and it's thorough. I do think that probably to keep it somewhat digestible, we'll focus on or maybe our favorable intermediate risk and below cancers, and then we'll also focus on people with at least a 10 to 15-year life expectancy. Then, of course, there's going to be an extended spectrum, right? Your 82-year-old is at three heart attacks and a stroke and comes in with a grade group 5. Okay, fine, we'll watch you, but all right, fantastic. I love it. You started out with family history, germline testing. The numbers I have are 12% metastatic, 4% or 5% localized. I do think dialing in on that history, as you mentioned, is critical. One of the things that I actually find a bit confusing to patients sometimes is comparing and contrasting genomic testing and germline testing. Does that ever come up in your chats with patients?

[Dr. Ashley Ross]
Yes, it comes up all the time. What I explain to them is, well, and actually I should say more for that, it comes up with providers all the time too. Right now, the NCCN, when it looks at things that predict how the cancer is going to behave, it looks at prognostic tests. It gives a level-one certification of evidence for genomic tests, specifically, Decipher is the only one in that category. Then, it talks a little bit about Artera AI, which is a newer test that hasn't yet been validated outside of radiation patients, but that looks at the digital pathology. Then, it has a level 4 evidence, meaning there's just one study not corroborated about genetics, but that genetics that they're talking about, those studies are looking at not only things like BRCA, but we're seeing the emergence of polygenic risk signatures that can tell you what's your SNP signature that's going to tell you the individual beyond your family history, if what's going to happen in terms of developing a cancer.

Regardless, for your actual question, providers are getting confused in there too, but for the patient, what I tell them is your genetics is what you inherited from mom and dad. It drove their predisposition to developing this cancer, and more so, in some cases, the cancer itself can be driven by that genetic abnormality. Genomics is better said as a test looking at what your cell is doing. What's it doing in terms of what genes are turned on? What's driving it? I don't go this deep with the patients. They usually accept that and we go to the next step, but sometimes when patients are really confused and they say, just explain it to me even more simpler, I tell them that, look, your body DNA is like the Library of Congress. You're not allowed to check out any books from the Library of Congress. It has all the information in the Library of Congress and that's your DNA, but the DNA is all the knowledge. Then, what your cell is doing when it wants to do something, it goes to the Library of Congress and it starts Xeroxing pages, like the instructions of what to do, and it takes that away. Those Xerox copies are your RNA. If I want to know what the cell's doing, I can look at the RNA. What are they Xeroxing from the Library of Congress?

If the patient still looks confused and they're like, well, I still don't get it, and I'm feeling a little bit punchy, I'll say, hey, have you seen that movie Seven? They say, oh yes, that's a great thriller. I'm like, okay, how did they catch the killer? How did they know it was him? They were like, oh, they looked and saw, what books did he check out of the library? I was like, great. The books they checked out of the library in that case was the RNA, the whole library is the DNA. We want to know, are your cells killers? Did they check out the wrong books from the library, or are they not? I got to feel pretty punchy to have the discussion derail to that point. Usually, I'm just telling them that genomics is looking at what the cancer, your cancer specifically, is doing right now. Or what its biological potential is. Not like, what did mom and dad give you that then caused this seed of cancer to develop?

[Dr. Aditya Bagrodia]
I like that, and I might have to start using the Library and the Seven analogies. Those totally resonate.

[Dr. Ashley Ross]
I love it.

[Dr. Aditya Bagrodia]
Germline testing, genomic testing, which we'll talk about, there's the MRI, there's the cores, there's a core involvement, the pattern for the variants, PSA density, which I'm sure is also something that you're factoring in. There's a ton of information that we have. One practical question, especially for the folks coming in from the outside with their biopsy in the community, not MRI, and let's say you get an MRI, nothing overly offensive, does surveillance for you start at that time of initial biopsy, or do you like confirmatory biopsies? Or is it case by case?

[Dr. Ashley Ross]
It's a great distinction you're making because even in the literature, for those that go through the literature, sometimes you're looking at literature where they're talking about a "surveillance series," but it's actually studying the period of time where you're qualifying that man for surveillance. A lot of times, just to your point, I'm telling the gentleman, like, we want to figure out, are you actually qualified for surveillance?

Let's say the guy comes in and has anything but very low-risk prostate cancer. Very low-risk prostate cancer, I know the AOA is getting away from that definition a little bit, but the NCCN definition of very low-risk prostate cancer, which just, if there's trainees and residents on, or just as a refresher, was originally developed to find out what would be the pathological correlates on a sextant biopsy that would equal like half a centimeter or so of low-grade disease. To reach those criteria, you had to have, of a sextant, less than 3 cores involved, less than 50% of a core, all Gleason grade group 1. We know a lot about those guys. We have more than 20 plus years of information on those guys. All that information says it's safe to follow them and that information came even before MRI was used in practice, right? Those guys also, from the beginning of your talk, and I think you were setting us up for this, I almost never diagnosed that in my practice because I use my MRIs and stuff. An MRI, again, for the group, is not to, it is to get the best biopsy you can get when you do a biopsy, but more so as a public health issue is to eliminate doing a lot of unnecessary biopsies, right?

Those guys almost never exist, but let's say everybody else, let's take our guy with like three or more cores of Gleason grade group 1, or our guys with 3, 4, 7 disease, grade group 2, I'm telling them, first, I need to qualify you for surveillance. The evidence says that we can watch this. If they had not gotten an MRI, I usually do an MRI about six months after their initial biopsy, sometimes earlier if I really think something is wrong, but I want to survey them, so sometimes three months. In less than three months, I will find a lot of artifacts, so six months is usually my goal. Sometimes three months is early. Then I do a fusion biopsy to qualify them for surveillance.

Let's make it easy on us and pretend the guy came in and they've already had the MRI, they've already had the biopsy, and now we have their biopsy results, and then we're going to talk about qualifying them for surveillance. The reality is that surveillance should be offered to basically everybody with favorable intermediate-risk disease and less. It definitely should be offered, but as I said before, what the patient wants to know is where are they going to be on these curves. Are they going to be on the curve that's flat that they never need treatment their whole life?

The ProtecT study, other series have suggested that for low-risk disease, that might be up to 50% of the patients. Of favorable intermediate-risk disease, that might be up to 25% of the patients, depending on age and other factors. Are they going to be on the disease curve where it's going to take them a while to progress, but we're looking at like three years or more of surveillance before we have to think about progression, and that might be a win for the patient of good sexual function, et cetera, and progression will be slow enough that we can treat them to cure. Or are they going to be on the curve where within one year or a couple of years, half of them or more are going to have progression to something we really don't want, with 4+3=7 disease, T3b disease, disease that is going to be less curable?

In this regard, the person who comes in, and we're trying to figure out what's what, and I should tell you, we don't absolutely know, because, in the surveillance trials that have gone on, they've had faults in two ways. One way, we were just understanding surveillance since the '90s till now in the PSA era, and we were scared about following cancers. Even if they got a little bit worse, people were coming off surveillance. That was one problem, so we really don't know, you know, when to do what. Then the other problem was, in other series, they were allowed to progress on surveillance in a way that at least, this side of the pond or in the US, I would find sort of unacceptable, like lifelong ADT or something from a guy who was curable is not a win for me. Particularly as we extend surveillance into my guys, there's no age cutoff for me.

Even if you're 40 or 50, you can be on surveillance in my practice, but as I extend it out, I want to know, well, what's our goal? I break down the risk factors into risk factors dealing with disease biology and risk factors that deal with disease extent. The disease extent risk factors, in my mind, I give them like one point or yellow flags. Those are things like PSA density, which is a measure of disease volume, PI-RADS-5, which is a measure of disease volume like I mentioned before, 1.5 centimeters or EPE, number of cores involved. Those are all one point. Then, the two-point things are things that have to do with your disease biology because these are things that give you metastatic potential, like incurability potential. Those things are, we mentioned intraductal cancers, cribriform can be more aggressive, if the guy was a known BRCA2 mutated guy, but then importantly, then one of the topics today is their genomics. Specifically, Decipher is the most validated, like I mentioned, NCCN gives it level-one evidence backing its ability to be prognostic for metastatic progression. Most of us around the US are using Decipher as our genomic test of choice.

Listen to the Full Podcast

Use of Genomics for Active Surveillance with Dr. Ashley Ross on the BackTable Urology Podcast)
Ep 107 Use of Genomics for Active Surveillance with Dr. Ashley Ross
00:00 / 01:04

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Tailoring Surveillance Strategies in Prostate Cancer

With no current black-and-white guidelines dictating where the line between continued surveillance and treatment initiation is drawn, the significance of shared decision-making and individualized risk assessment becomes paramount in guiding prostate cancer surveillance protocols. For low-volume, low-risk patients, a general framework involves periodic PSA monitoring, rectal exams, and selective MRI confirmatory biopsies. However, this approach cannot be applied to all low-risk patients, highlighting the need for ongoing research to refine risk assessment criteria.

In patients with high-risk features like PI-RADS 5 lesions or with Gleason grade group 2 scores, extended-spectrum surveillance may lead to unfavorable outcomes due to the more aggressive nature of these disease paths. Thus, the integration of clinical intuition with shared patient-clinician decision-making ensures appropriate interventions that are tailored to unique patient risk profiles.

[Dr. Aditya Bagrodia]
They're so comprehensive, Ashley, that I don't even feel like interrupting, but just a couple of thoughts. Early on, when I started out as an independent practitioner, 2016, surveillance, of course, had been here, but extended spectrum surveillance, higher volume grade group 1, younger patients were still a little bit dicey. I mean, I was paranoid. I didn't want somebody to go from curable to uncurable under my watch. I still feel that way.

I mean, you talked about your three trajectories. Trajectory A, which is rapid progression. I feel like we're able to identify those patients, or we certainly need to make an effort to identify those patients. Then the other two trajectories are, it's a flip of a coin, protect 15-year data, out 15 years, 50-70% chance of requiring treatment, which is, it's kind of a hard concept for me to convey to a patient is that we're starting out on surveillance, but there's a really good chance that you may not end up on surveillance. Even going back to what you were mentioning about qualifying patients, I've gone from algorithmic reflex biopsies at X, Y, and Z intervals, to also engaging in shared decision-making. That's going to take in all of the factors that you'd mentioned, the density, the core involvement, the MRI. If there's EPE and it's grade group 2, I'm nervous, but some of those, and biopsy tolerance. If the person is like, that was the most miserable experience of my entire life, that actually counts a little bit to me. I actually will start bringing in some of the things like genomic classifiers in those basically non, very low-risk patients, which I think it's a bit of a disservice that that's gone because it was like, okay, you're good to go, rock and roll, barring anything catastrophic, you're going to be fine, but for my higher volume grade group 1, younger patients, or favorable intermediate risk, even trying to decide what our schedule of PSAs and MRIs and biopsies is going to be, I find it useful sometimes to have some information. Any comments on that?

[Dr. Ashley Ross]
Yes, I think two things. One is, if you do see them, just like you mentioned, I'll just tell you what I'm doing for my low-volume, low-risk patients. For everybody, I'm doing a PSA every six months and a rectal exam every year, and so I'm seeing them in the clinic at least once a year and just touching base with them. My low volume, low-risk patients, as you mentioned, what I'm doing for them is I'm telling them if everything else looks hunky dory, no doubling of the PSA, no new clinical exam findings, then I'm telling them at two years, I want to get an MRI confirmatory and do a biopsy. If that still shows small volume, low-risk disease, then that is the last biopsy you're ever going to have on surveillance because we found your disease by accident and we're going to treat you like someone who's just getting prostate cancer screening with the exception of we're going to do your PSA twice a year instead of once a year. I completely agree with you on that.

For my other low-risk guys, I think we just don't know. I'm trying to put together a trial and it's just taking me a little bit longer to get it right, which can give us a framework so we can understand for the people who are into research, what are the different coefficients of these risk factors, but I agree, shared decision-making around do we need to do the biopsy or not. To your point, in real-world practice, it's based on a lot of factors. Is your MRI clean? Like when you get it again, is there disease you can't see? Is a PSA density looking like it's 0.1 or not? Did you start out with just a few cores of Gleason grade group 1 disease? Is the patient getting older? As you get more data, one of my mentors, Dr. Carter was working a lot on this. Obviously, the patient's risk changes every year that you confirm stability of disease, or every multiple years you confirm stability of the risk changes, so I completely agree with you. I do think, even though you can skim the people off the top pretty well, because like you said, you're not old, you're not young, you're sort of top of your game, mid-career guy, some people, as surveillance gets more accepted, it's important to tell some of the patients, this isn't for you. Like you mentioned, the PI-RADS 5, 3+4=7 disease guy, you're going to get burned. The PI-RADS 5 Gleason grade group 2 Decipher high-risk guy, you're going to get burned hard. I can just tell you, that patient is going to be unhappy with you. You're going to have to do surgery plus radiation the next year, or you'll have to do radiation plus ADT the next year. Just for the audience, there are some things that you just, if you have multiple, it's like soccer, sorry for all the analogies. You got, multiple yellow cards or some red cards, you got to get that guy out of the game.

The other people, like you said, our job now as investigators at academic places, but certainly, for people in private practice, they take all the information together. That low genomics risk guy, I remember ProtecT was evaluating people, I think every four years or something like that, and maybe a little bit loose, but I think there's something to be learned there. Take all your factors together and have shared decision-making with the patient. If the biopsy was uncomfortable, try to find out from them, where was that discomfort. Most of mine are transperineal biopsies I do in the clinic, but some people just feel better just going to the OR. That's a little bit of a bigger run for a short slide, but some people need it. You're definitely right, your threshold, being in practice longer builds your intuition. You can have that intuition and you can definitely share decisions with the patient, but never, this is a hard thing, but you never want to hold back too much. Like if you feel in your gut, this guy really needs a biopsy, sometimes the patient's kind of talking me out of it. I know that it's a shared decision, but you actually can see what's going to happen to them sometimes better than they can see, right? That's why we did residency.

Podcast Contributors

Dr. Ashley Ross discusses Use of Genomics for Active Surveillance on the BackTable 107 Podcast

Dr. Ashley Ross

Dr. Ashley Ross is an associate professor of urology and clinical director of the Polsky Urological Oncology Center at Northwestern Feinberg School of Medicine.

Dr. Aditya Bagrodia discusses Use of Genomics for Active Surveillance on the BackTable 107 Podcast

Dr. Aditya Bagrodia

Dr. Aditya Bagrodia is an associate professor of urology and genitourinary oncology team leader at UC San Diego Health in California and adjunct professor of urology at UT Southwestern.

Cite This Podcast

BackTable, LLC (Producer). (2023, July 19). Ep. 107 – Use of Genomics for Active Surveillance [Audio podcast]. Retrieved from https://www.backtable.com

Disclaimer: The Materials available on BackTable.com are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.

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