top of page

BackTable / Urology / Article

The Modern Role of Genomics & Imaging in Prostate Cancer Diagnosis & Treatment

Author Olivia Reid covers The Modern Role of Genomics & Imaging in Prostate Cancer Diagnosis & Treatment on BackTable Urology

Olivia Reid • May 26, 2024 • 91 hits

Advancements in genomics and imaging are revolutionizing the diagnosis and management of prostate cancer by minimizing overdiagnosis and tailoring treatments to individual patients. Urologic oncologists Dr. Aditya Bagrodia and Dr. Ashley Ross discuss genomic tests and imaging techniques that can distinguish between benign conditions and significant cancers; this helps to minimize unnecessary biopsies and reduce patient anxiety.

For patients with confirmed prostate cancer, comprehensive evaluations encompassing genetic factors, advanced imaging techniques, and detailed pathological assessments guide treatment decisions, with genomic classifiers playing a crucial role in determining the most appropriate management strategy. These approaches enhance diagnostic accuracy, streamline treatment processes, and improve patient outcomes by aligning care strategies with the cancer’s biological behavior.

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

•Incorporating advanced genomic tests and imaging methods optimizes prostate cancer diagnosis by minimizing unnecessary biopsies. These tests help to stratify risk and allow for more accurate identification of candidates for active surveillance versus those requiring immediate intervention.

•MRI-guided biopsies, complemented by biomarkers like the Prostate Health Index (phi), enhance diagnostic precision and reduce the overdiagnosis of low-risk cancers.

•Thorough evaluation post-biopsy encompasses review of genetic factors, staging via MRI and prostate-specific membrane antigen (PSMA) PET, the use of Decipher, and detailed pathological examination to guide treatment decisions.

•Genomic testing offers superior accuracy over traditional Gleason grading in predicting disease behavior and metastasis risk.

The Modern Role of Genomics & Imaging in Prostate Cancer Diagnosis & Treatment

Table of Contents

(1) Differentiating Between Benign & Malignant Prostate Cancer

(2) How Diagnostic Tools Inform Treatment in Prostate Cancer

(3) The Practical Applications of Genomic Classifiers in Prostate Cancer Care

Differentiating Between Benign & Malignant Prostate Cancer

Current guidelines recommend moving beyond the traditional PSA test to incorporate interim biomarkers like the Prostate Health Index (phi), followed by MRI to enhance diagnostic accuracy. These steps help distinguish between benign disease and clinically significant prostate cancer. Implementing MRI-guided biopsies can decrease the detection of low-risk cancers that often lead to overtreatment. However, the practical challenges of MRI, including cost, patient discomfort, and variable quality, necessitate standardized certification for radiologists and centers. Transitioning to bi-parametric MRI could streamline the process, making it more accessible and efficient.

[Dr. Aditya Bagrodia]
I think when we talk about surveillance, it's hard not to make it a little bit of a PSA screening talk in diagnostics, but when patients are coming in, let's just say, elevated PSA referral, in your ideal world, what transpires between an elevated PSA and say, for instance, a biopsy?

[Dr. Ashley Ross]
That's actually a great point and a great starting point. I think that where this dovetails in, as you were kind of leading to, is we're trying to avoid the diagnosis of what would have been classified as NCCN, very low-risk prostate cancer, or let's just say, small amounts of low-grade prostate cancer. In many ways, we're trying to avoid that entirely. That's a disease that obviously should only be surveyed as a management option, but it'd be better just not to diagnose this and not to give patients anxiety over it.

How do you avoid that? The AOA just came out with their new guideline statement, and they maybe weren't firm enough. I mean, honestly, in every situation possible, you should be doing something else between the PSA and a biopsy, and that something else should eventually lead you to an MRI prior to the biopsy, as long as the gentleman doesn't have some contraindication, like a pacemaker that's not compatible.

At my institution, we have access to the Prostate Health Index. Not everybody has that, but as a biomarker, I tend to like it. It has a much better sensitivity and specificity than PSA alone, and it's dirt cheap, so it's really of low cost. If you don't have that, there's a bunch of other tests on the market that can help sort of determine, is this PSA due to a large prostate inflammation, or is it really prostate cancer-related? Now, you may or may not take that step of this interim biomarker. For me, like I said, Prostate Health Index, under 27, I don't do anything else. I just watch the guy. You know, you could use percent-free. Percent-free over 25 is a good sign. However, that only captures a small fraction of the population. Other people use things like MIPS or 4K score or other tests out there, including exome and DX, but then I think that you want to do a MRI.

Now, MRI is where there's really, like quite frankly, level one evidence that it's going to help us, and it's going to help us by reducing biopsies by over 30%, maybe even up to 50%, and if we do a biopsy, it's going to help us with its positive predictive value and targeting. In my shop, I tend to do all my biopsies with MRI guidance. Essentially, ideally, the patient would have an elevated PSA, maybe an interim test, but then go to an MRI. If the MRI is clean, PI-RADS 1 or 2, defer a biopsy. There's a lot of people with a PI-RADS 3 score that could defer the biopsy. Then some PI-RADS 3, most of your PI-RADS 4 and 5, because remember, we should only be PSA testing people who we think need it, like 10-year survival, et cetera, you're going to want to do a biopsy to figure out what's going on.

I think that that, to your point, sorry to be long-winded, you're going to limit the detection of clinically insignificant disease, and you're not going to miss clinically significant disease or just miss a small fraction of the men that might have clinically significant disease that you'll probably pick up the next year as you follow them.

[Dr. Aditya Bagrodia]
That's perfect. I think it's going to get increasingly more interesting and complex as some of these secondary prostate cancer screening tests and their results, which maybe led to an MRI and a diagnosis of an indolent prostate cancer, may factor into all of the bits of information, which of course, we're going to cover here extensively as we think about surveillance, surveillance regimens, and counselings for the likelihood of coming off of surveillance. I think bottom line, ideal world, PSA, MRI, MRI ultrasound fusion biopsy, whether that's transperineal, transrectal, cognitive, or actual fusion, in-bore, that's kind of the best case scenario, and I would agree.

[Dr. Ashley Ross]
I should note, there's one thing, you know, people have asked me, what's the limitation? What's keeping us from that? I think that there's a few major things, and I know it's not the topic of this podcast, but since we have a listening audience, and something that I think I have to double down on myself, now that I really see the problem: MRIs have a few problems in prostate land. They can be expensive. They can be hard on the patient because they're about an hour if you do with contrast. There can be access issues, and again, with contrast, that makes it an hour. Then finally, there can be quality issues, where the quality MRI is not good enough for a fusion, the quality of the read or the MRI sequences itself is not good enough for an adequate interpretation, or the reader is not qualified.

I think this year, I always try to have at least one or two missions in my back pockets, something I want to push forward. I think this year, one of those missions is really lobbying, whichever way we can, right now, it's a grassroots thing through your BackTable urology, that the AUA get together with the American College of Radiology, and say, you know what, we need a way to certify readers, certify centers, to do prostate MRIs, so we can have some consistency. Then the second part is, I think we really need to move towards bi-parametric MRI like Europe has done for screening. That means drop the contrast. That way, there's no nurse needed in the MRI suite. Some places require radiologists there when you have the contrast from contrast reactions. No nurse, 10-minute scan, easy in, easy out, increases the capacity thus by about fivefold. I know that's off topic, but I think that that's one of the things that we should all be thinking about in our head is, do we really need to be doing triphasic multi-parametric MRI?

[Dr. Aditya Bagrodia]
I think everything you mentioned, and on top of that, I'm not young, and I'm not old, but for practices that may be a little bit more mature, getting an MRI for a PSA, interpreting that, having the infrastructure to actually act on that is not a foregone conclusion. Now you're taking a bread-and-butter urologic diagnosis, like an elevated PSA, and you're referring that out. I don't mean to sound like people have nefarious interests there, it's just adoption of a new technology. You and I might not think of it that way, but it could be for the other dude, just like doing Haifu or robots, et cetera. I guess we talked about the ideal, and then there's going to be a very real patient who comes in with a 12-core biopsy and they've got some type of prostate cancer.

[Dr. Ashley Ross]
Right.

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

Earn CME

BackTable CMEfy button

Stay Up To Date

Follow:

Subscribe:

Sign Up:

How Diagnostic Tools Inform Treatment in Prostate Cancer

When a patient presents with a biopsy-confirmed prostate cancer, a thorough and nuanced evaluation is crucial for guiding management decisions. The evaluation focuses on understanding the etiology, staging, aggressiveness, and potential treatment pathways. Genetic factors, such as DNA damage repair protein abnormalities, play a significant role, especially in high-risk cases. Accurate staging relies on MRI and PSMA PET scans to assess both local and distant disease. Detailed pathological examination, including core length and involvement assessment, informs the disease extent. The Gleason grade, particularly the percentage of pattern 4 and the presence of cribriform or intraductal variants, further stratifies the patient’s long-term risk. Genomic testing, such as Decipher, provides additional insights into the cancer’s biology, helping to tailor treatment or surveillance strategies.

[Dr. Aditya Bagrodia]
We'll probably talk a little bit about both of those scenarios and next steps and so on and so forth, but maybe starting with the patient that comes in from the outside, who's got a biopsy demonstrating prostate cancer. Talk to us a little bit, like using a fine tooth comb, every bit of information that you're gleaning at that point and everything that you're going to be obtaining to help make your management decisions.

[Dr. Ashley Ross]
Usually, I'll kind of frame it from the way I talk to the patient, and that fills in what the rest of it is. The patient who comes in with prostate cancer into your office, wants to know four things: Why did they get prostate cancer? How much is in their body, the stage? How aggressive is what they have, and what are we going to do?

The first thing I tell them is why they got this prostate cancer. I tell them most likely it's because they're male and they got a little bit older. Those are the two biggest risk factors. There can be a genetic component, and that obviously depends on the aggressiveness of the prostate cancer for high-risk disease or metastatic disease. We're looking at 5% to 10% will have some kind of, like, DNA damage repair protein abnormality, and sometimes people who have localized disease have a strong family history. I'll put male, increased age, and then I'll put genetics, and I'll ask them a little bit. Do you have a strong family history of breast, ovarian, pancreatic cancer, or prostate cancer in the family? I'm trying to tease out, obviously, BRCA2 is the big component, and also see if they're a candidate for germline testing. We can get into that a little bit later.

The second question is, okay, now you want to know how much is in your body, and that's the stage. I talk to the patient a little bit about nowadays, we think about the stage both like we always used to, are you clinically localized or are you metastatic, but also we think about, well, what's the bulk of the disease in your prostate? This comes back to our MRI discussion. If you are a practitioner who's getting an MRI first, you've got some idea of local regional staging when the person comes in. If you haven't done the MRI first, then I think that that's important to understand local regional staging. Even if today's topic is on surveillance, even if we're thinking about surveying a person, that comes into play. For the audience, probably familiar, but PI-RADS 5 lesions, for example, in the definition, it has to be 1.5 centimeters in size, or the radiologist has to think there's definitive extraprostatic extension. There was a nice paper by Lenny Marx's group at UCLA that looked at PI-RADS 5 lesions and surveying them. He found that half of them would come off surveillance within two years with 4+3=7 disease. Then also focal therapy, which you might get into today, also is contingent upon that if you're adopting that in your practice. So I'll say, okay, we want to understand your stage distantly and locally. Distantly, if the person has unfavorable intermediate-risk prostate cancer or above, we're looking in their chart to see, well, did they do some kind of staging workup for distant disease? Myself, I would use, again, I'm kind of privileged, I'm at a large center, and I've only really practiced at large centers or in metropolitan areas, but a PET PSMA is now my standard for the unfavorable intermediate-risk prostate cancer and above. They get their local imaging with their MRI and their distant staging is PET PSMA. If they haven't had that, have they had a bone scan and CT? I'm talking to the patient about that and I'm also bringing up the PET PSMA at that time too if they have unfavorable intermediate-risk disease and above.

If they have favorable intermediate or low-risk disease, so the Gleason grade groups one and two, and then I'm talking to the patient about, well, what's the local stage in your prostate? I'm looking at the chart to see what did the other guy feel with their finger for their T-stage? I'm looking at the patient's records to look for that MRI and how much burden was there. I'm sort of looking at the pathology report too, to understand what's the volume of disease. If I'm really on my game when I'm looking at the pathology report, I'm not just looking at the number of cores involved, but I'm also looking at, if it's available, if they made measurements of the cores. Not just like you had a core and it was 40% involved with 3+4=7 disease with 10% pattern 4, but was that core 1.5 centimeters in length? Was that a fragmented core that was 3 millimeters in length? I think actually, a lot of our efforts right now, I know that everyone has high-in-the-sky stuff for digital pathology and that maybe it's going to be even prognostic and this or that. I think one of the early metrics we're going to get is some better idea of volume of disease and quantitative disease amount: benign versus cancerous. Regardless, that's what we're looking at for the stage, and what the patient wants to know, I know that's not the question for the audience, but the patient wants to know is, are they clinically localized where I'll then draw a little squiggly line to make equals curable, or are they metastatic where we're looking at containable?

Then the next question is, okay, if it's clinically localized, like most of our surveillance candidates, obviously, then the question is, well, how aggressive is it? There you're looking for the Gleason grade as the first metric, and you're telling the patient, well, what does it look like under the light microscope? The Gleason grade groups are nice to talk to the patients about. I usually draw 1 and 5 on both sides. 1 gets a smiley face, 5's a frowny face, and I show them where they are. Say the guy's a 2. Then for 2, I say that's in the old system, that's 3+4=7. 3 is the best. 4 is like some more aggressive stuff. What's the percentage of pattern 4? Should be looking at that. We're going to talk about surveillance. Over 20-25%, I think is a bad sign. Is there any pattern 4 variants? There's not a lot of research here, but the research we have says that cribriform pattern 4 might be a little bit more aggressive. Intraductal might be a worst candidate for surveillance, and intraductal might be associated with genetic predisposition for prostate cancer. Then I talk to the patient. I say everything to understand risk is what we're going to talk about a bit later, which is what are the blueprints of the cells looking like? What goes beyond what the cells look like under the microscope, which can be somewhat subjective and also can't really inform you fully of the biology. Can we look at the gene level with some kind of genomic testing? We'll get into that later. I tend to use Decipher in my practice, and that can stratify you more so.

Then finally comes the million-dollar question. What are we going to do? What we are going to do is based on the patient's health preferences and what we think the disease is going to do if treated or untreated. Usually, the first question there, which I think I'll stop and let you bridge into the next thing, is the question of do we need to treat or can we observe as our initial strategy? If we observe, what I tell the patient is we're going to be on, with the idea that your disease is going to be on one of three lines. We should picture an x-axis of time and a y-axis of getting worse. If we choose surveillance, all cancers, pretty much, are going to get worse. The question is if there's going to be a threshold of treatment. I usually draw a dotted line on the horizontal y-axis and say this is the threshold that everyone's going to agree you need to be treated. Your line could be a line that progresses with such a slow slope that you never need treatment. Or your line could be a line where you're going to need treatment in the next five years where we're going to see it coming and we're going to treat you without missing any opportunities. Or your line can be like a logarithmic takeoff line, in which case, one year from now or two, you're going to reclassify and reclassify in a way that we would have wished we had treated you earlier. The question is, how do we determine which one of those three lines, really kind of flat, gradual slope, or like logarithmic, are you on? It's really long-winded. I'm sorry for that Aditya, but that's where we are.

The Practical Applications of Genomic Classifiers in Prostate Cancer Care

Physicians must consider disease extent, aggressiveness, and appropriate treatment strategies when managing prostate cancer. Genomic classifiers like Decipher provide crucial, objective data to aid these decisions. For instance, genomic testing can confirm suitability for active surveillance for Gleason grade group 1 (low-risk) patients. A low-risk Decipher score supports continued surveillance with fewer biopsies, while a high-risk score necessitates more vigilant follow-up or treatment consideration. Furthermore, in unfavorable intermediate-risk cases, Decipher breaks risk down into categories of low, intermediate, or high. Low-risk results support surveillance, whereas intermediate or high-risk scores prompt earlier intervention. For Gleason grade group 2 or higher, genomic testing refines treatment strategies.

Streamlining the treatment process decreases both patient anxiety and the overtreatment of clinically insignificant cancers. Explaining genomic classifier results helps these patients understand the rationale behind surveillance and its quality of life benefits. Integrating genomic classifiers into clinical practice enhances decision-making, provides insights into the cancer's biological behavior, enables personalized treatment plans, and minimizes unnecessary interventions.

[Dr. Aditya Bagrodia]
You know, it's that exact scenario. Maybe we'll run through some common clinical scenarios to frame this a little bit, but just a couple of thoughts. I mean, absolutely. Sometimes it takes somebody, something additional to convey the aggressiveness of this and something objective that's not read by a pathologist or sampling error by a urologist, et cetera, like a genomic classifier can be useful. On the flip side, I have these highly educated, super healthy people in La Jolla that are like, "Doc, it's cancer. I want it out," and I'm trying to walk them off the ledge and saying, “hey, Mr. So-and-so, I understand your concerns and this is going to be a dynamic process for the first time you heard cancer, you're freaking out and you don't want to die, but over time, you're going to understand the quality of life implications, et cetera, but let's be deliberate. Let's get some additional information and maybe this will help ease some of your fears.” I've found that if I'm going to get a genomic classifier, that it's incredibly helpful to run through what the output is going to look like and actually run through what my thresholds are to do something. Otherwise, it becomes extremely abstract and confusing to try to sit with the man and say, here's your likelihood of metastasizing, dying, et cetera. Can you talk to us a little bit about how that works for you?

[Dr. Ashley Ross]
Honestly, as I mentioned, I use Decipher as my genomic classifier. I don't usually even show them the report. I mean, there's some rich information on there, but they just have to understand at a high level, you know? What I tell them is if they're Gleason grade group 1, I tell them that what we're looking for is really, you're a good candidate for surveillance. If that Decipher comes back low risk, I tell them it's going to come back low, intermediate, or high. If it comes back low risk, we know you should stay on surveillance and maybe we can actually space out your biopsies. If it comes back high risk, you're in this minority population and we have to really be hawkish if we're going to follow you. Most of my Gleason grade group 1 guys, I follow. I tell them that, look, you will likely progress, but I usually will follow them up to a year. For some of them, that's the guys that I actually take to radical: the rare people in my practice with Gleason grade group 1 or the Decipher high Gleason grade group 1, and usually, they have one other yellow flag. An intermediate risk, you know, is middle of the road. If I look at the Northwestern data and I look at what's the frequency of people I would never want to follow, the pathology at radical is 4, 3, 7, or T3b. For intermediate Decipher, then, I mean, low-intermediate than high, it goes from about 15% to 30% to 40%, so intermediate actually has some real risk. Regardless, I've already decided to myself, if this guy has a low-risk Decipher, and they're even up to Gleason grade group 2, favorable intermediate-risk disease, I'm going to tell them that surveillance is a really viable option. If they have low-risk cancer, like Gleason grade group 1, and the Decipher is low, then basically, you shouldn't do this with the data, but you can do this with the sort of talking head stuff, so I pull out whatever I need to do. Like, I tell them, look, you got low-grade disease. We found it so early, it probably doesn't want treatment, and I tell them one of two things. What I used to tell them is, look, I took an oath, and the oath was to do no harm. Me doing anything to you right now, when I have no idea if your cancer is ever going to get worse, is doing harm. I can guarantee you it's going to harm your sexual function in some way. Even my people who have "perfect erections," if I really drill down on it, that is it exactly like it was before surgery, they'll say, well, no, it's a little bit off or something like that, and I'll know it's a little bit of harm. Or even if something, God forbid, happens to them, it's a little bit of harm. I tell them I can't do it. It's against my Hippocratic Oath. Or now, Dr. Eganer, Kupferberg, and others have given us this debate about, is Gleason grade group 1 even cancer. I tell the guy, hey, guess what? There's this debate: should we even be calling this cancer or is it a precancerous lesion? Just to help them put some buzzwords in. They'll go home, if it's like you said, that educated La Jolla guy, they'll Google something, they'll get on that New York Times article, and they'll be like, oh, yeah, this isn't that bad. The reality too, if I explain to them the curves that we were talking about, if they're on that curve C, which is that they can go their whole life and never need treatment, there's no way that we want to pass up that opportunity.

On the flip side, if I really see those warning flags there, then I'm telling them we have to maybe have to do treatment. In some ways, like I said, for that low-grade disease guy, it can be on the other end where you just know the patient's going to be in a bad shape. To your point, I think that pulling out your cards, this genomics really helping us, and it's not just that they're more objective, they are, it's, you know, actually, in almost every study, they are superior to the Gleason grade, which makes sense, right? You're looking at the phenotype from Gleason, even if you have Epstein reading it, he's looking at the phenotype, the genomics is looking at the molecular biology, and particularly Decipher that started out with the genome-wide signature, and then drilled down into what really is driving metastasis or bad potential. It makes sense. The reason that you're against genomics, not you, I mean, one might be against genomics, is this idea of cost. Is there a cost to the patient, cost of the system? If it can help you collapse decisional uncertainty, make it such that your first move is your best move, you're actually going to save the patient costs, save the system cost, and save the patient's life in some instances.

Again, a compound answer, but I agree that genomics helps you on the bookends, on two sides, it helps you de-intensify and understand cadence of surveillance, meaning how often you're following, and intensify. One other thing I should say, which is I've heard some providers say, well, I know what to do, and I don't need the genomics to help me. If we're talking about special tools, genomics, MRI, other stuff, they're like, I know what to do, I don't need the genomics, it's a rare case I don't know what to do. That is like, I won't say any French, but that's a bunch of hooey, right? For me, the approach I take is, I want to get all the information I can on you and your cancer so we can make our best decision. I don't know unless I get the information, I don't know. Now, I'm a little bit on the side of I think, in my practice, like I said, I like to collapse decisional uncertainty, so I sometimes will be an over-tester. For example, PET PSMA, I know it's not the conversation, but for staging, I use PET PSMA on my unfavorable risk, intermediate risk and high risk, and above. Because I want to know if I'm going to go in for that surgery, is it going to be curative or not? Some of my colleagues say, look, I'm going to do surgery on this guy no matter what. I don't need to stage him with something that's going to show me that they're not curable by surgery. I guess so, but for me, I'd rather give the guy a realistic expectation of what's going to happen to him before I make the decision but everyone varies in these ways. Actually, this comes up to like, there's no standard in how we qualify people for surveillance, how we do the surveillance, what takes someone off surveillance. Actually, like I mentioned, for the trials, I think that it's, again, just to plug myself, I'm really trying to put together something for a trial that we can do nationally, where one of the key elements is that we're going to have a committee decide if someone's really progressed on surveillance or not so that the patient can understand it's not just them and their provider.

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.

backtable-earn-free-cme.jpg
backtable-plus-vi-cta.jpg

Podcasts

Use of Genomics for Active Surveillance with Dr. Ashley Ross on the BackTable Urology Podcast)

Articles

Topics

Get in touch!

We want to hear from you. Let us know if you’re interested in partnering with BackTable as a Podcast guest, a sponsor, or as a member of the BackTable Team.

Select which show(s) you would like to subscribe to:

Thanks! Message sent.

bottom of page