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Ashley Ross: Hi, and thank you everyone for joining us. I'm Dr. Ashley Ross. I'm an Associate Professor of Urology here at Northwestern Feinberg School of Medicine. I'm accompanied today by two experts in prostate cancer, Dr. Preston Sprenkle, who's an Associate Professor at Yale. Also, the Director of Urological Oncology Fellowship at Yale and Urological Oncology Research there. And Dr. Randy Vince, who's an Assistant Professor at Case Western, where he also specializes in urological oncology. Both of them have a lot of experience in the topic we're going to be speaking about today, which is active surveillance and risk stratification during active surveillance for prostate cancer among men. Dr. Sprenkle. Dr. Vince, thank you for joining us.

Randy Vince: It's a pleasure to be here.

Ashley Ross: I think that we can start off maybe, Dr. Sprenkle, with defining what is active surveillance. I know that it should be a routine part of all of our practices, but it'd be nice to kind of understand what is it as a modality.

Preston Sprenkle: Sure, yeah. I think it's important to distinguish active surveillance from watchful waiting. A lot of patients, and even I think physicians, can mix those up, but active surveillance isn't active monitoring. And so it is taking close tabs on someone's prostate cancer. We typically use this for men with favorable risk prostate cancer, so low or favorable, intermediate. I'm sure we'll talk about that some more, but it is a process of periodic PSA testing and periodic prostate biopsies. The interval of those seems to vary. There are different protocols. I can tell you at our institution, we do PSA testing every six months and repeat. We do MRI fusion biopsies, and we'll do those at least once a year initially, with a potential to space those out if people risk-stratify into a lower, very low risk of progression on some of our interval testing.

Ashley Ross: So as you're mentioning, the idea is that the cancer is not quite aggressive enough to need treatment or warrant treatment now. It may reach that point in the future. We want to figure out how do we monitor it so that we can still intervene with curative intent, so that they don't have metastatic progression, for example, or death from prostate cancer, but they're sparing the morbidity when they can. And in that line, Dr. Vince, how do you counsel your patients on what a win is on surveillance? Is it one year on surveillance is a win, three, five? How do you counsel them towards that?

Randy Vince: Yeah, that's a great question, Dr. Ross. So I think for me, I tell patients any amount of time where we can spare you treatment-related side effects and not have any disease progression, it's a win. Apparently in this situation nationwide, where PSA testing has gone down since the Preventative Services Task Force recommendation, because we were over-treating so many people, and so to me, I tell patients all the time, if we can spare your treatment-related side effects and still be able to intervene if necessary, then that's a win. And most patients, when you talk to them about the treatment-related side effects of definitive therapy, whether it's radiation or prostatectomy, they say, I'm all in. If you're telling me that you can intervene if my disease progresses and still have curative intent like you said, but you spare me additional time of not having to deal with the treatment-related side effects, I'm willing to do it.

Ashley Ross: Now, obviously the worry is that there's going to be some patients where if they have a fast progression, you might miss it, or there may be patients that have inevitable progression within a year or so, and then they wonder, well, the disease did get a little bit worse. It's not incurable, but I might have more sexual side effects now than later. We'll talk a lot about risk stratification, but before we get into that, Dr. Sprenkle, how do you counsel your patients about what is your expectation and what do you want for them to enter surveillance? And what are patients that you would tell them you really are not a surveillance candidate? How do you go about that discussion?

Preston Sprenkle: So I think you alluded to risk stratification. That's key. That's the biologic rationale for surveillance is based on risk stratification. I think there are some patients who have a tremendous amount of anxiety about having a prostate cancer diagnosis. I honestly spend a lot of time with those guys, trying to convince them that their risk is not as significant as they think it is. And there's a lot of data, I'm a data person, not all patients can hear data and listen to it, and it's an emotional decision. So most of those folks, I'll say, "Listen, think about it. Let's talk about this again." But I think we have really good data now that observing cancer for a period of time is very, very safe, especially in low risk disease.

Ashley Ross: So in regards to risk stratification, there's a couple of things that I think about, and I'm thinking about a recent paper that you had where you looked at different features of risk ratification, and sometimes when you have such a homogeneous group, it's hard to tease out who might be at danger. And so I know in your publication, you looked a little bit about genomics, and Dr. Vince, when you were in the MUSIC Registry, and I'm sure now in your practice, you used some advanced testing and obviously confirmation of the disease as well. Maybe I'll start with you, Dr. Vince, talk a little bit about how the MUSIC Registry, what that was, what they did on surveillance there, how they used advanced testing for disease risk in that situation, and then if you could, stay on that for a little bit and talk about what you're now doing in your practice at Case Western.

Randy Vince: Yeah, absolutely. So for those who might listen to this who are unfamiliar with MUSIC, it's really a quality improvement collaborative within the State of Michigan. And the efforts were to kind of standardize and make Michigan the leader for prostate cancer care. And so now, that collaborative has grown, and it's over 90% of the urologists within the State of Michigan are also within that collaborative. And so within establishing it, what it did was it established the infrastructure to prospectively collect data, all with the goal of improving patient outcomes. But when it comes to active surveillance specifically, they came up with what they titled the MUSIC Roadmap, which is a active surveillance pathway, and within that, they get confirmatory testing for anyone who is considering active surveillance. So that means with the confirmatory testing, either you're getting a repeat biopsy, a prostate MRI, or some type of genomic testing.

And so what we did was we looked at those men that underwent Decipher biopsy testing over the course of four years, and we specifically honed in on two groups of patients. One was those patients on active surveillance, like we're discussing here, and another was those patients undergoing definitive therapy. But specifically when we talk about active surveillance testing, among all of those men who underwent Decipher biopsy testing, what we found is that the median time spent on active surveillance was significantly shorter for those men with high risk Decipher scores. It was approximately 20 months shorter compared to those men with low or intermediate risk Decipher biopsy scores.

The other thing is that those men who were on active surveillance, whether you adjust for things like NCCN risk, age, percent of cores positive, what we found is that a higher Decipher risk score was also independently associated with progressing from active surveillance to treatment.

And so that was the study that we did that was published in I believe it's 2021. But in terms of how I incorporate it for my personal practice, typically, any person who has favorable intermediate risk disease, I'll get Decipher biopsy testing done. I don't use it as much for some of my low risk patients, because a lot of those patients that I place on active surveillance, I've found since coming to Case Western, they might only have one or two cores positive out of 12 or 16 cores. And so for that reason, I don't typically use Decipher testing to decide whether or not we're going to do active surveillance. But for those gentlemen who may have a few cores, a few extra cores of Gleason 6 and maybe a PSA that's approaching 10, then I'll start to consider it, and it'll be an informed decision-making process where I'll counsel the patient on the potential benefit of using Decipher biopsy. And based off of the information I give them, if they decide that this is something they want to proceed with, they'll let me know, and then that's how we'll do the testing.

Ashley Ross: Yeah. A couple of things about your study that I thought were interesting was one, sometimes you would think, "Well, if they got a Decipher test, which for the audience, you're probably very familiar, but it's a expression-based test looking at the mRNA, and it has a prognostic signature output. Some people could say, "Well, if they got the Decipher test, and they saw that it was high risk, maybe they would get scared and come off surveillance more," and that's why there was more progression to treatment. But even you showed in your paper that the people that had Decipher high risk that went to treatment, also had all the biochemical recurrences after treatment. So there were also the people that were not necessarily as curable by just one-stop shopping for that.

It's interesting, you were mentioning your population for, Dr. Sprenkle had a nice series that you had shown recently, and which I'm going to have you talk about a little bit, where everyone coming into the series had an MRI-informed biopsy. I think a better way of saying at least we're trying to have a full assessment of what is going on. You may have inherited some patients, Dr. Vincent, that came from an era where they had some non-targeted biopsies, and then you can catch some of these lower risk guys. Dr. Sprenkle, in your paper, you took a sub-cohort that had Decipher, and just take us through some of your findings there as well.

Preston Sprenkle: Sure. So we ended up in this cohort, we kind of sub-selected the favorable intermediate risk patients that we include in the paper to only include those with a small volume of pattern four in a single core. We have other patients on active surveillance with higher volume than that, but in this cohort, it was pretty quite favorable for the favorable intermediate, and then low risk patients, so Gleason 6. We did find that the Decipher scores, these are all gentlemen as you mentioned, who had had a MR fusion biopsy, were on active surveillance, and we looked at their genomic Decipher score and sort of what happened on subsequent biopsies. And we did find that the Decipher score sort of by a 0.1 or 10% increase was associated with an increased risk of progression. This held very true for men with low grades, so with Gleason 6 prostate cancer. And we defined progression as a grade increase, so going from grade one to grade two.

We did not find that the Decipher score significantly predicted progression in men who had grade two disease, which was kind of interesting, but by our definition of progression, that meant that they were going to grade three. And so there were not a lot of men, honestly, that were included in that. And almost all the men with grade two disease had a low genomic risk, because those are really the only people that I keep on surveillance. I don't keep people with a high genomic risk score on surveillance if they have intermediate grade disease.

Ashley Ross: Now, you were mentioning risk counts and having multiple features is more important than having one. So the very low risk guy with a high Decipher is very different than favorable intermediate risk and high Decipher.

Preston Sprenkle: I agree. I think to what you're saying, based on the Decipher risk categories, yes, we did see a stepwise increase in terms of the correlation of risk of progression in men, and there definitely was a more than 50% of men on surveillance with a high Decipher would progress.

Ashley Ross: Let's talk a little bit about something else here. So I think that we all like the risk stratification features we sort of agree on. I'm wondering a little bit about utilization of surveillance in your different areas. You've gone from being in Michigan and the MUSIC Consortium, you recently published a nice article talking about comparing that to SEER, looking at uptake of surveillance. Maybe talk a little bit about what you found there, Dr. Vince, and then talk also a little bit about what it's like at Case Western. What have we learned from that?

Randy Vince: Yeah, so for the article that you were mentioning, where we looked at the MUSIC population and we compared it SEER data, what we wanted to really look at was initially when we did the analysis, there was a higher percentage of patients with favorable disease. They were risk disease in MUSIC that were undergoing active surveillance compared to nationwide with SEER data. And that was just at one specific instance. But we said to ourselves, "Well, as MUSIC is a quality improvement collaborative, and we know that we should be offering active surveillance for men with favorable risk disease," from the inception of MUSIC, where were we when we first started with active surveillance within MUSIC compared to the SEER data? And then after we implemented these protocols, as well as value-based incentives for placing men with favorable risk prostate cancer on active surveillance, what was the trend compared to the rest of the nation?

And what we found is that after implementing these initiatives, that the rates of active surveillance use within this population went up substantially within MUSIC. However, there was kind of a slow drift nationwide. And so what it did was it allowed us to say that these types of initiatives and protocols could increase active surveillance utilization nationwide. When it comes down to what we do here at Case, and we're trying to work on this, it's not as standardized across the board as it was when I was at University of Michigan within the MUSIC collaborative. But that takes buy-in, and the system is set up a little bit differently, because we have over 25 hospitals within this one particular health system that I'm in now. And so while that's the push, it's not as standardized, but eventually it will get there.

Ashley Ross: And Dr. Sprenkle, what's happening at Yale? Just what Dr. Vince said, I find that at my institution it's like we're trying to get towards standardized in a protocol, and we think it's been increased surveillance like he did with MUSIC. How is it like at Yale, right now?

Preston Sprenkle: It is relatively standardized, and largely because within the health system there are a limited number of us that do the vast majority of the biopsies, and so we are kind of directing and then counseling the patients after their biopsy, "This is sort of what our protocol is." I think there's still a fair bit of variability. We are tracking the patients that we follow, which is self-fulfilling. But the ones that we lose and are being tracked elsewhere, we don't have as good a hold on what's happening there. So I think as an institution, we were pretty standardized in how we're following at the moment, but there's definitely some variability.

Ashley Ross: Well, I can't thank you guys enough. I know it's been quite a wide-reaching discussion, but I think it's going to help our audience quite a bit. Thank you both, Dr. Sprenkle and Dr. Vince, for your time today, but also your contributions to the literature and your championing of not just surveillance, but say precision care to optimize outcomes overall in quality of life for all of our men out there with prostate cancer. I really enjoyed talking to you both today.

Randy Vince: Great. Thanks a lot, Dr. Ross.

Preston Sprenkle: Thank you.