Practice Patterns of Active Surveillance in Prostate Cancer - Matt Cooperberg

March 14, 2019

Alicia Morgans and Matt Cooperberg discuss the current state of contemporary active surveillance and efforts to standardize strategies nationwide. This conversation also includes discussion on informed decision making and practice patterns of active surveillance and how to tailor based on biology and genetics


Matthew Cooperberg, MD, MPH, FACS, Associate Professor, Department of Urology, UCSF Helen Diller Family Chair in Urology, the University of California, San Francisco

Alicia Morgans, MD, MPH Associate Professor of Medicine in the Division of Hematology/Oncology at the Northwestern University Feinberg School of Medicine in Chicago, Illinois.
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Alicia Morgans: Hi, I'm delighted to have here with me today, Dr. Matt Cooperberg, a urologist at UCSF. Thank you so much for coming to talk with me today.

Matt Cooperberg: Pleasure.

Alicia Morgans: You know, one of your passions and interests both in research and in clinical practice, is active surveillance. And you've really been a trailblazer in that arena. And I would love to hear your thoughts on where things stand now, in contemporary active surveillance. What's the data? Where are we going? Are we ever going to be able to standardize this process, to really widely distribute the practice across the country?

Matt Cooperberg: Sure. 2018, 2019 has really been, I think a great news phase when it comes to, how we're managing prostate cancer in general. And I think for active surveillance, specifically. I think after years of practice patterns not being well aligned with tumor risk, we're finally seeing movement toward a much more appropriate risk adapted management paradigm. Where more and more low risk prostate cancer, which kills almost nobody ever, is being managed with active surveillance. And high risk diseases being managed more aggressively with surgery, often combined with radiation therapy. Reflecting a whole host of studies which have come out in the last few years.

You know, active surveillance has been seen as an academic endeavor until really the current decade. And even though some of our centers have been really pushing this concept for 20 years. It's really just in the last few years we've seen things changing. And after many years of pervasive over treatment, we're finally seeing, I think the message getting across in broader community practice, that the preferred management strategy for low risk prostate cancer is active surveillance. And that really should be full stop. We're not quite there yet, but we're really seeing multiple lines of evidence that we are getting there.

So, we had a study at a couple of years ago from the National Capture Registry, showing rates of surveillance up to about 40% by 2013. That was echoed in a large study out of Michigan, where they've got pretty much every practice, every urology practice in the state contributing patients. They were up to about 50% across the state. I've heard rumors are now over 60.

The National AQUA Registry, which the AUA has been running since 2014, also rates around 50%. And most recently it was a paper out from this new SEER Active Surveillance database out of Harvard, which confirms the same findings. And you know, the paperwork made this big splash because, it was in JAMA, but at the end of the day it was really just confirming the same findings that we are up to about 50% across the country. Which is a lot of progress in the right direction. We should be at 80%, which is where Sweden is. But it really is rapid progress in the right direction.

This is 50% of low risk disease. This is not focusing in on the so called very low risk population, or really trying to sub-stratify low risk disease based on MRI, based on biomarkers or any of those other refinements. And those things do have their place. But at the end of the day, we know from trials like PIVOT, that low risk disease by the old school D’Amico classification really does not progress, and kills very, very few men with minimal management.

And now we have guidelines both from ASCO's endorsement of Clinical Care Ontario, and this joint AUA/ASTRO/SUO guideline. Both of which now say pretty clearly that surveillance should be standard of care for low risk disease.

Alicia Morgans: Absolutely. You know, I think this is fascinating because, it's actually driven by several factors though, right? So, it's the physician's comfort with active surveillance and that's something that, it sounds like the education has been getting across, right? Because these rates are picking up.

But there's a lot of this whole decision making of active surveillance. It actually is driven by patients too. And we were talking just a few minutes ago about how that message needs to be clear to patients. That active surveillance is actually an active process. It's not, "You have cancer, but you don't need to do anything. I'll see you in 10 years." It's an active engagement of the patient with the provider, over time to make sure that if there is more aggressive disease over time, that would be detected.

So, can you tell us a little bit about that, and how you maximize that partnership in your clinical practice?

Matt Cooperberg: Yeah, absolutely. I think what's driving the trends is actually mixed. I think it's partly a better physician education, and more specific guidelines that are endorsing surveillance more clearly.

Alicia Morgans: Yes.

Matt Cooperberg: And it's also, I think the word getting out into the street. It was not that many years ago that, I would see men who've had five different consultations, with five different urologists and radiation oncologists. All of whom are lining them up for treatment next week, and I'm talking to them about surveillance and you know kind of had this, "What do you mean you're not going to treat my cancer?" Sort of reaction.

And I think we see less and less of that. At least in the practices that are drawing around academic cancer centers, and that sort of thing. Because I think the word is on the street. I think patient communities are much more aware of active surveillance, as a means of maintaining quality of life. And are much more aware of the fact that the risk of cancer progression is really very low.

But as you say, active surveillance is active. It is not synonymous with watchful waiting. And one of the important lessons from the PROTECT trial, is that active monitoring, which is what they called it, just PSA. So PSA surveillance in that study is not adequate. Is not going to catch the progressive tumors adequately enough, to get us to the same kind of a disease outcomes that we would expect to see with immediate treatment.

So, traditionally it's been a biopsy every year. We've been really interested in trying to tailor those regimens. I think a lot of practices have more or less de facto, been stretching out their interval to at least every two years. But we really want to get to the point where we can customize it beyond that. If you think about every 100 patients or so that come in with low risk disease, and look like they could be eligible for surveillance. If we think about gestalt numbers, and it's hard to pinpoint these down specifically, but you know, we think about half of those men will eventually get treated within the next five or so years.

But it's actually can get much more subtle and gradated than that. I mean, if you think about those hundred men. There's probably no more than five or 10, who really have under sampled aggressive biology, that we can pick up with an MRI or a biomarker, or something like that, who really should go straight to immediate treatment.

You've probably got about 40 or 50 who should be on the surveillance protocol, because sooner or later the cancer may progress and we need to catch that event. I then you've had a big pool who frankly could be on more of a watchful waiting paradigm, who we should think about this more like a colonoscopy and be able to say, "Go home, come back in five years. Don't worry about this in the interim”.

We have a paper actually from the Canary Consortium, which is nine major centers across North America that were presented, actually last year at this meeting for the first time. And we'll be submitted very soon. Showing that we can do exactly this, by looking at just the clinical information available in standard practice. Never mind what more we can do with imaging and biomarkers.

So I think this is going to be the future is not just selecting men for active surveillance, but trying to tailor surveillance based on everything we've learned about their biology.

But that is an area where the community does need to catch up. There was a great study, another great study for the MUSIC Registry in Michigan. Where they looked not just at the rate of active surveillance uptake, but the quality of surveillance. So, they just asked the question of men going onto surveillance, embarking on surveillance over the next 18 months, "How many get an adequate number of PSAs. And how many get at least one confirmatory test?" And they took a broad view of this saying either, biopsy or they would accept a genomic test or an MRI as a biopsy replacement. Which in and of itself is a pretty liberal view on things.

And the numbers were low. You know, there's something like 30% across the board. This is Amy Luckenbaugh’s paper. And it was really, I think a bit of a wake-up call that, "Okay, well the next quality measure we really need to go after, is quality of surveillance."

Alicia Morgans: Yes.

Matt Cooperberg: So, MUSIC has taken the lead on this and they've got four CMS approved quality measures now for active surveillance. And we've actually adopted those in AQUA as well. So, this is the National AUA Registry. We now have those same measures. Looking at uptake of surveillance, adequacy of assessments on surveillance, and rate of transition to active treatment among men who starts surveillance. These are really, I think, the multiple metrics by which we're going to start to evaluate surveillance quality now in a very serious way across the country.

So, one other important finding from the studies that I mentioned, both the MUSIC and the AQUA studies, looking at practice patterns, have still found pretty pervasive variation. So, even though the rates of surveillance across the board are in this 40 to 50% range, and rising pretty quickly. You still see a lot of variation from practice to practice, and from individual provider to provider.

So, the likelihood of getting active surveillance ranges from practice to practice, from about 25 to nearly 80%. And from individual provider ranges from zero to 100%. Meaning that your likelihood of getting offered surveillance ranges, really exceptionally widely depending on who you happen to see. And of course, that remains a major problem.

It's hardly unique to active surveillance. We see it everywhere in prostate, cancer management, urology, and frankly everywhere in medicine. But as we start to develop real quality measures, this is exactly the sort of variation that we hope to reduce.

Alicia Morgans: That's great. So, you know, really to raise the bar, we've got to have metrics in place that we can strive to meet. We have to measure them, find our gaps, meet the gaps, and continue the progress.

So, I commend you and the folks who are working on this. Really to standardize approaches to active surveillance that cannot just occur in a single center here or there. But can be really a disseminated across practices, across the country, to raise the bar. So, thank you so much for sharing your insights on this approach to treatment.

Matt Cooperberg: Always a pleasure.

Alicia Morgans: Thank you.

Matt Cooperberg: Thank you.