Melanie Cole, MS (Host): Prostate MRI is reshaping biopsy decisions and cancer detection. Welcome to Better Edge, a Northwestern Medicine podcast for physicians. I'm Melanie Cole. And today, we are highlighting improving prostate cancer detection with prostate MRI. Joining me is Dr. Hiten Patel. He's an Assistant Professor of Urology at Northwestern Medicine.

Dr. Patel, thank you so much for joining us today. So, how has pre-biopsy prostate MRI changed detection and biopsy triage in your clinic over the last, say, five years or so?

Dr. Hiten Patel: Yeah. Thanks for having me on. And I think this is a very important topic in urology and prostate cancer in general. So, prostate MRI has really completely changed how we detect prostate cancer. We use prostate MRI to now often determine if someone needs a biopsy at all to detect prostate cancer. And it also impacts how we do the biopsy. [00:01:00] So, two things, I'll touch on those two points.

So with Ashley Ross, who's one of my senior partners in urology and the urology and data analytics team, we actually created a risk calculator, the NMRI risk calculator that can give a more precise estimate of risk. And it's available online and also in our electronic medical records. And so, when that calculator and MRI suggests that there's about a 10 or 15% or less risk of having a clinically significant prostate cancer, that usually is my threshold to say, "Hey, maybe you don't need one," or we can continue PSA screening without having to jump to that test.

And the second way that prostate MRI can change how we perform detection is that we can target lesions that the scan identifies on biopsy. So, that reduces the risk that we miss something significant on the biopsy. So, we used to do a template biopsy of different areas, but now we say, "Hey, there's a lesion here. Let me direct a needle to that area. And that makes it less likely we might miss it on biopsy." And then, so that's how it's really changed my practice of detection care. You know, there's other areas that it's changed a [00:02:00] little bit too. So, we can monitor changes on MRI. So, just because we didn't do a biopsy now doesn't mean we can't repeat an MRI later if someone has changes or if they're on active surveillance for low risk cancer.

And then, some other nuances, how we study and improve prostate MRI, we can get into as needed, but there are studies on do we need to use contrast or not on the MRI? Is it biparametric good enough compared to multiparametric? And then, there's some issues around false positive or negative scans. So, this are areas where PSMA PET tracers or AI or artificial intelligence applied to MRI may help us in the future. And so, not what we're using a hundred percent yet in clinical practice, but things where we still have exciting places to go.

Host: So, can you expand just a bit on where that PSMA PET scan fits into this algorithm?

Dr. Hiten Patel: Yeah. So, MRI's pretty good by itself. I mean, it's much better than transrectal ultrasound was by itself. But there are still some areas where radiologists may say, "Hey, that spot looks intermediate or looks equivocal. We're not that sure that it's really prostate [00:03:00] cancer." And we think there's some opportunity there to say, "Well, if we incorporate other decision factors, one of them could be PSMA PET, which is right now used for staging for higher risk prostate cancers. But there's data now coming out if we combine MRI with PET. And Dr. Ted Schaeffer has a study, a trial, that we've published data on now for higher risk patients, can that really help us find these lesions and say, "Okay, that area really is more suspicious"? Because the PET tracer also lights up in that area they weren't sure about on MRI. And vice versa, maybe the MRI didn't show a spot, but that PET tracer's picking up some activity, does that mean that there's some prostate cancer there? So, PET may help us also direct biopsies to important areas, similar to how we've learned from MRI in the last 10 years.

Melanie Cole, MS: It's such an exciting time in your field, Dr. Patel. So, give us an analysis of VA data that you led. What did the VA data show about MRI use over time and which operational levers really were more reliably and raise that [00:04:00] adoption for use?

Dr. Hiten Patel: In the Veterans' Health Administration-- so, I have a part-time appointment at the Jesse Brown VA and a partnership between Northwestern as one of the academic affiliates for the VA. We, as part of a DoD grant, evaluated administrative data across all VAs. And it's in a recent publication that we actually did find that overall uptake in prostate MRI was very steadily increasing since 2016. And so, a lot of seminal trials came out around that time in 2017. And it rose essentially from nothing to about 40% in recent years or last year. And so, this increase over time paralleled or actually was maybe even slightly better than use from data sources like Medicare and other health insurances. So if anything, the VA's doing as good or potentially slightly better. But forty percent is, you know, obviously not near a hundred percent. And the question is, where should it be?

And so, I think this use in the early period of the paradigm is essentially based on provider acceptance. So as we're becoming more comfortable using it, are we willing to change how these prostate biopsies are performed for decades by urologists? [00:05:00] And how comfortable are we at looking at MRIs and performing these targeted biopsies, which is a different skill that didn't exist 10 years ago?

And so, guidelines are now acknowledging prostate MRI and recommending it more often. And so, with the data that's increased, I think that's going to help. And obviously, it's helped a lot to get to even 40% now, but for more urologists to be able to accept and say, "Hey, This is part of my practice," and having data that shows it improves detection and outcomes for patients.

Melanie Cole, MS: So then, Doctor, as prostate MRI use has increased over time for veterans, some disparities still remain. And despite overall growth, what patterns or gaps in the VA data surprised you the most? And based on those, what are the implications for clinical practice at the VA and non-VA settings?

Dr. Hiten Patel: Yeah. So honestly, overall uptake has been very steady, and I hope it continues to do so. But part of our research is how to make that better and how to make that more equal. And so, our analysis so far found that the slower uptake was actually seen in patients in rural settings. And so, these are settings [00:06:00] where it may be-- And we have to do more research to figure it out-- is it that they just don't have access to MRI or is it the providers locally aren't used to using it? And so, I feel like there are a lot of more imaging centers-- and quality. So, our question is going to be, are the barriers-- which may vary by site-- is it because the provider's not accessing it? Or there's some issues on just even having an MRI scanner available? And the last thing could be radiologists with experience reading MRIs. These are things that if you were trained before the last 10 years, these are patterns and things on the MRI that were not taught or not picked up. And so, there may be some extra training that's needs to be done on both the urology and radiology side. So, that's one part is that rural veterans seem to have less access or, at least, have less use right now. But it's not as bad as it could be. And I think, you know, it's hopefully going to keep getting better as we work on it.

And the second part is that I think is more concerning is that Black veterans have a little bit lower use of prostate MRI. They're still increasing over time. But what was concerning is that they presented with higher PSAs than other veterans. And so, even though Black men or veterans were getting [00:07:00] prostate MRI, at a slightly lower rate, they had higher PSAs, which means their risk was potentially a little higher. And we know Black men in the United States have higher risk of prostate cancer in general. And so, the next goals would be to see if there are some regional or center-based, which sites-- actually, I target opportunities to address the slower uptake and make it more equal.

Host: So, do you have some strategies that you'd recommend to overcome some of these challenges quickly instead of it taking like a long time? Do you have some practical strategies that could help with some of these obstacles?

Dr. Hiten Patel: So, some strategies of how to overcome this, and I think This is the most practical part is to find out where the gap is. So first, I think you do need access to urologic care. And so, having a urologist who gets trained in how to perform targeted biopsy and know how to use an MRI, I think that's key because if you don't have that, then there's no point in doing the MRI to begin with. So, I think that's the first part. And I think urologists are getting better at that. So if you're a urologist who's interested in doing that, I think that's the place to start.

And then, second is the partnerships with [00:08:00] radiology. So, it depends on how your practice model works. At Northwestern, it's a little easier that we have radiologists we work with directly. They're part of the same center. But in private practices, maybe that they're working with reimaging centers that are a little separate. They may not know the radiologist. It's hard to communicate. So, I think establishing some communication with radiology to say, "Hey, this is what we need. We're going to send our patient's here to get these MRIs." We need to be able to get that information in an accurate way and to then be able to use it. So, I think setting up how to do targeted biopsies in the clinic, and then using the information the prostate MRI gives you by working with radiology is going to be very helpful to make sure you trust what it's showing, and then how to actually get that into your clinic.

Melanie Cole, MS: Those are all really workable solutions, Dr. Patel. When MRI targeted and systemic biopsy grades are discordant, then tell us your management algorithm given the intermediate risk signal. Do you have a recent case that illustrates this approach? Tell us about that.

Dr. Hiten Patel: We have a recent [00:09:00] publication. We didn't lead it, but we were one of 27 centers that participated. And there was some data from several centers that was put together in a publication that showed that if you had a grade on the systematic part of the biopsy, the template part that is not related to the MRI and compare that to what you found on the targeted biopsy on the MRI, the risk of the cancer is actually kind of in between the two. If they both show the same thing, then now we know exactly what we're dealing with. Sometimes the targeted biopsy finds something the systematic biopsy missed or undergraded, And what we found is that the risk is a little lower than what the targeted biopsy shows, which is reasonable. It's still a clinically significant prostate cancer if it's Grade Group 2 or higher. But in those cases, we're a little more comfortable with considering active surveillance for these patients, where you say, "Okay, we did find Grade Group 2, a clinically significant prostate cancer, but we have a little bit more comfort of watching those men on surveillance similar to how we do for Grade Group 1 or lower risk prostate cancer."

So even though grade 2 is not low risk, these men when they're discordant-- you know, I had a patient that targeted biopsy show that [00:10:00] they had a Grade Group 2 prostate cancer, the systematic biopsy actually was either negative or low risk in some areas. And so, that man, we followed on active surveillance. And that would be an option that, I think, five, ten years ago we would not have offered this person.

And similarly, I've had another patient that I shared with Dr. Ross that had a targeted biopsy showing a significant cancer, a systematic biopsy that showed actually no cancer at all. And we were more comfortable considering that maybe they should consider focal therapy as an option opposed to treating the whole prostate. And so, I think these are places where men would've either had to more strongly think of radical surgery or radiation therapy that now when you have some discordance and the targeted biopsy and systematic biopsy, I think that gives me a little bit more of a confidence that, "Hey, the cancer really is localized in that targeted biopsy area," and we can offer maybe a broader management approach.

Host: That's so interesting. So, thinking about lesion characteristics, how do they guide decisions on repeat sampling, confirmatory testing, treatment intensity? [00:11:00] As you were speaking about active surveillance, and what would dictate that, how do those lesion characteristics guide those decisions?

Dr. Hiten Patel: The important characteristics of radiologist gives us on the lesion is exactly where it's located. Is this something that we can reach easily? If I missed it on biopsies, is it because I just couldn't target that area with a needle correctly? And that would induce me to say, "Hey, we, maybe we need a repeat sampling or a different approach of how to get to that spot on the next attempt if the PSA keeps rising."

But the main thing the radiologist is going to say is, "How big is that spot?" Is it one centimeter, two centimeters in size? And what is the BI-RADS score? This is a score that classifies risk. And 1 and 2 basically mean that it's a negative MRI. There's no highly suspicious areas. A 3 is equivocal. And 4s and 5s are high or very high-risk of cancer being present.

So, if I have a man who had a BI-RADS 4 or 5 lesion, and it was negative, we still need to pay a little bit more careful attention to it, especially if their PSAs rising. If it's a BI-RADS 3 and it's negative, patients often ask [00:12:00] me, "Well, why do I have a spot on my MRI? If you're going to do a biopsy and show that there's no cancer, why would it be there?" And that is an artifact of imaging and it's an equivocal spot. But those, I'm more likely to trust and say, "Hey, that's unlikely a prostate cancer. We don't need repeat sampling." And of course, if the PSA is going up, we can reevaluate. But those I'm a little bit more trusting of.

So, BI-RADS is one characteristic. Lesion size is the other that I think is very helpful. And then, same thing for treatment intensity. If someone had a BI-RADS 3 lesion with significant prostate cancer, but it's a small volume, they may be offered active surveillance. Whereas if it's a BI-RADS 5 lesion, and they have a higher risk prostate cancer Grade Group 2 or higher, I'd be more likely to treat whether it's radical therapy or considering other options.

Host: How should clinicians approach decision-making after a negative prostate MRI? And what role does PSA density play in guiding whether to defer or proceed with that biopsy? How are you counseling patients and even referring physicians in this [00:13:00] situation?

Dr. Hiten Patel: For most men with a negative prostate MRI, I'm fairly comfortable. We usually use prostate health Index and PSA density augments even before the MRI. And so if somebody had a low prostate health index or low PSA, density, we might consider, "Oh, do we need to work them up further?" But I think a prostate MRI for most men is going to help.

And then, the combination of saying, "Hey, you have a negative MRI and your PSA density is low, or your prostate health index is very low," I'm very comfortable watching those men because they have a low risk of having a significant prostate cancer and continuing PSA screening. Now if someone had a high PSA density, I think that's important to say we should keep a closer eye. But for most men with negative MRIs, I'm comfortable with research by Dr. Adam Murphy, our clinical cohort and his trials, we found that Black men, despite a negative prostate MRI, still have higher risk of clinically significant prostate cancer compared to Caucasian men or men of other races.

And so, I think that's important. If Black men, especially if they have any family history or need some more guidance on a real PSA density cutoff, it [00:14:00] should be lower for them than Caucasian men to say, "Hey, maybe we should still do a biopsy or we at least need to watch you more closely." And so, that's something we're trying to improve. We have some research on the AI side of saying for the patient's who have false negative MRIs, patient's who had negative MRI, we did a biopsy and still found cancer. Why is it negative? And so, with Lee Cooper and others who's in a digital pathology PhD lab, we're working on that to see can we figure out these characteristics and can we go back to the imaging, which is what Ulas Bagci, another AI in prostate cancer researcher does and can we feedback and say, "Well, was this a really a negative MRI or did the radiologist not see a lesion that was too small or looked similar to the background? Is there variation?" And so, I think these are tools that are going to come out that are going to help us. But for now, I use PSA density and prostate health index, as kind of my characteristics. And then, the patient factors, they have a family history, or they have African American ancestry that could increase their risk.

Host: Dr. Patel, this has been so informative and really interesting. This is such [00:15:00] an interesting topic and I'm excited to learn more as you develop more of these algorithms. So, what top three actions would you recommend urologists implement now to standardize MRI ordering, reporting, and follow through across VA and non-VA settings?

Dr. Hiten Patel: I guess number one would be working with radiology. And that's really feedback. And so if you get a prostate MRI result providing feedback, and I think Adam Murphy did this in our Jesse Brown VA, is to work with radiology and say, "Hey, these are cases where we had a high-risk lesion, but the biopsy was negative. Is there something that explains why we're we overcalling lesions?" And then, same thing with negative MRIs. "This is a negative result. But I still found cancer. Can we work with radiology to give that feedback, and improve the flow?" And so, that's one.

Second is, and it's not harder for urologists to control, but it's MRI availability and throughput. Different centers will have access to different MRI scanners, but working and trying to figure out, "Hey, if we start doing this on patients that weren't having it, the centers may just not have [00:16:00] the ability for throughput." And so, finding options for your patients of where they can get scans done and considering if you need contrast, it's faster scans if you do it without contrast. We have future research on using AI to decide should you even get contrast or not as an idea with Ulas Bagci that our prostate cancer score may focus on in the future. But that's part of it, is can we make use of the resources we have for MRIs?

And then third, which is on the urologist, is to implement targeted biopsy. Getting comfortable with looking at the MRI and whether your radiologist circles your lesion or not. And then, being able to direct the needle to perform a targeted biopsy. That's a skillset that I think is required now and is something that we have to learn ourselves.

Melanie Cole, MS: Great information, Dr. Patel. What a great guest you are as always. Thank you so much for joining us today. And to refer your patient or for more information, please visit our website at breakthroughsforphysicians.nm.org/urology to get connected with one of our providers. That concludes this episode of Better Edge, a Northwestern Medicine Podcast for physicians. I'm [00:17:00] Melanie Cole.