Prostate Cancer: Active Surveillance

[music] >> Hi everyone, thanks for having me. Uh I'll be going over active surveillance, what it is, what we consider. Uh we'll talk about kind of clinical risk stratification and treatment selection, what to consider when choosing active surveillance versus other treatment options, and then stepping out a little bit to how it's been used across the country, and then our experience here at UCSF. So, I'll go through all this uh quickly. Now, a big busy table on the left side, but basically when we talk about prostate cancer, we have to stratify or break it up into groups, low risk, high risk, intermediate risk. And that's not just based on your PSA or your Gleason score, but all those other factors. So, when we, the urologist, talk to you about low-risk disease, high-risk disease, we're taking into account all those things that we did, all the tests and the labs, and grouping you into different uh categories. This is the graph that we kind of refer to, or excuse me, the table, and this helps guide not only how we think about your disease, but what options may be available or most uh best tailored for you. And this is largely based overall on the aggressiveness of disease, and gives us an idea, not a crystal ball, but an idea of the risk of outcomes afterwards. And from this uh part of NCCN guidelines and other guidelines as well, is providing recommendations for treatment. Now, um each department has grown significantly since I first developed this slide, but across the disease spectrum, you can see how all of us work together in different parts of uh the prostate cancer continuum, ranging from low-risk to metastatic disease. And you see that when it comes to prostate cancer treatment, there are many different options. So, again, shared decision-making, that taking the time to get information, discuss the treatment options, the risk and benefits of all of those are important. One of those, the one that I'll highlight today, is active surveillance. And what really does that mean? Often times, patients will think of active surveillance, and they'll say, "Well, if I'm not doing anything, then what's happening to the cancer?" And it's not so much that we're just sitting there and watching the cancer. We're actively monitoring you. So, different than the other term, watchful waiting, which some people may have heard, where you sit and wait for symptoms to develop. We keep you on a very strict protocol, and it allows us to avoid or delay the costs, functional cost or impact, monetary impact, time impacts of treatment without compromising your chance of cure. So, it's not a so much as a forever treatment strategy for everyone, but it gives us an opportunity to fine-tune when you need treatment. And this is really compliant with guidelines, and based on the initial assessment being accurate or reasonable. So, we need to have a very clear understanding of the disease, what it looks like under the microscope, where it is within the prostate, and that helps us identify who would be a good candidate for active surveillance, um and who needs treatment right now. So, when it comes down to it, it's really about timing. Going back to the table a few slides ago, you can start to see all the different factors that we consider when we talk about low-risk disease, or whether or not you may be a good candidate for active surveillance. That includes the PSA, the PSA density, which is the PSA divided by the size of the prostate itself, giving us more clues about the potential behavior of the disease, the stage, where it's located within the prostate, the grade, what it looks like underneath a microscope. And you may have heard others talk about Gleason 3 + 3 as being that low-risk prostate cancer, and that's traditionally where active surveillance has been thought of as being the preferred management strategy. But both here and other places, we provided more information to understand that for patients who may even have some component of Gleason 3 plus 4 active surveillance may be a reasonable option for them depending on the volume and the subtype. Uh now we've been able to incorporate MRI as well as further genomics so the DNA of the tumor itself and its behavior as well as age, health, preferences and I'll always add this one of confidence in your provider so understanding and comfort with the team taking care of you. The key components of active surveillance are many. Looking at the PSA the blood test several times a year. Imaging of the prostate with MRI or ultrasound once a year. A biopsy after the initial biopsy so you have the first biopsy that gives you the diagnosis a confirmatory biopsy to make sure that nothing was missed with that small needle. And then after that regular biopsies at hopefully broader and broader wider intervals to make sure that there are not microscopic changes in the disease over time. But with each of these steps we can keep a close eye on the disease so there's no chance for broad dramatic changes in the cancer. We're seeing you so much we catch microscopic changes before they have a chance to become a big problem. And now we have more information and guidance and understanding of the genomic testing that we can do to further stratify you or classify you further help tailor the strategy for active surveillance. So it's not kind of a cookie cutter one size fits all approach but really tailoring it to you and the disease that we're managing. And this is what we've seen over time. Going back even to the early 2000s we've seen that active surveillance over the country over the broad area of the country has increased over time going back from 2015 and 2010. We see that across different counties even we see a broad difference It's kind of a busy slide, but just know that over time things have increased even when we look at individual counties across the United States. We went even further in a study led by Dr. Cooperberg from 2023, I believe, even looked within urology practices across the United States at men with low-risk disease using the Aqua registry, which is our quality registry of urology practices across the country. This provided another aspect to look at active surveillance and how it's being used by urologists across the country. We saw again a broad uptick or rapid uptick in the use of active surveillance aligned with more information, greater understanding of low-risk disease, and the safety of active surveillance itself. We saw that when you look at clinics themselves, you see a broad variation or difference in how often they're using active surveillance. That depends part on the disease that they're seeing, the patients and their preferences, and the providers' preferences. But we're seeing an increase over time. And now we can even look down at the practitioner, people like me, in our ourselves, to see how often these patients are being managed with active surveillance versus surgery or radiation or some other treatment. The key thing here is that over time we see an increase in the use of active surveillance, which we've seen both in CAPTURE, our larger national registries, as well as in the Aqua registry. And things that we would expect are also driving the use of active surveillance, the age, the race, the PSA values themselves. Now, again, over time we've done less and less overtreatment of low-risk disease. So, for low-risk cancers, that first step, that initial treatment being active surveillance, is what our guidelines now recommend as that first step. So, it does warrant discussion with your providers to see if that's a good option for you Um, time of diagnosis. And what we can [clears throat] see as well as for each kind of a interesting graph here, but for each clinic in each provider, we're still seeing variations. So, this really hones in on the idea that every provider and every clinic may have a different pattern of active surveillance use. And that's where it's very good to ask questions about, am I candidate for active surveillance? Why not or why would this be a good option? What's their experience and what are they're seeing in their own practice? And what we see is when you start to take into account all the other factors that play into this other than just the biopsy Gleason 3 + 3, we see again that year of diagnosis, age, race, and PSA value are things that are associated with the chance of active surveillance versus other treatments. Now, our experience here within UCSF, thankfully we've, um, been able to track our outcomes in our own experience and we've seen that over time by the time we get out to 3, 5, 7 years, then nearly half the patients remain on active surveillance over that long duration. So, that doesn't mean that we've missed a window of cure, but we've avoided the potential cost, those side effects of treatment to maybe a time where it's much more, uh, needed. We've avoided over-treatment, avoided the risk of impacts to erections or urine control, um, earlier. And we see that survival outcomes maintain, uh, very high rates. Overall survival, cancer specific survival, as well as metastasis free survival within these cohorts are all well above 96%. When we look at our cohort specifically of the last 1,450 men, again, driving home the fact that active surveillance is a safe option and management strategy for those carefully selected patients, we see that overall survival, cancer specific survival, as well as metastasis free survival are all high uh going out to 77 months, so closer to 6 years, 6 and 1/2 years. Now, our outcomes within UCSF, if we look specifically at those patients with grade group 1, which is Gleason 3 + 3 disease, uh this is work done by uh Kevin Shi, our incoming fellow and our current resident, um when we monitor these patients over time, as expected, some of them will have changes under a microscope. And that's what we see in terms of upgrade, meaning a change in the Gleason score over time on subsequent biopsies. As expected, starting out with very low-risk disease or low-risk disease, you have a higher chance of change over time, so it's not surprising that we see uh rates of upgrade as we follow these patients out to 10 years, but very low rates of metastasis. And this really points to active surveillance being a good strategy, but there are being key factors associated with that transition from active surveillance to some definitive treatment, surgery, radiation, for example. And a lot of that is driven by the change in what we see in the biopsy, a change from grade group 1, that Gleason 3 + 3, to something higher, 3 + 4, 4 + 3, going on the same pattern. And that's really a shift from that low-risk disease or favorable intermediate disease now to unfavorable intermediate disease, and that's when you'll have that discussion of, "Okay, maybe it's time now for us to consider definitive treatment." We looked further at grade group 2 disease, so those who have a biopsy showing Gleason 3 + 4. And we saw that again, age, percentage of positive cores, and PSA density were all factors that help us understand who may be at greater risk of needing to transition from active surveillance to treatment. Other things that we use to understand in burden of disease, MRI, changes in MRIs over time, or genomic testing, testing the DNA of the tumor itself, were not things that were immediately associated with our changes in our outcomes. And what we saw is that when patients had Gleason 3 + 4, grade group 2, but were without the aggressive subtypes, expansile cribriform, intraductal carcinoma, these aggressive patterns under a microscope, that their outcomes were more favorable than those who had those more aggressive forms. Obviously, in this group compared to those who had Gleason 3 + 3, we saw higher rates of progression and higher rates of treatment, but maintained low rates low rates of metastasis over time. Big picture, what we see when we look at this specific subgroup of patients is a risk of disease progression for those who have a higher PSA density, one of those factors we talked about early on in terms of things to consider for active surveillance, MRI findings, as well as progression on biopsy as being factors really associated with again transitioning from active surveillance to definitive treatment with one of those options I discussed before. What we see over time is in this case either volume changes or Gleason grade changes. So, the biopsy findings themselves can potentially drive that shift again from that favorable intermediate disease eligible for active surveillance to now unfavorable intermediate risk disease, a disease that may require definitive treatment. Overall, active surveillance remains the preferred strategy for patients with Gleason 3 + 3 and those who have been carefully selected and accurately assessed at diagnosis. It's a clinical protocol of close monitoring rather than kind of leave it and forget it for those with favorable disease and portends favorable outcomes long term. And we see that nationally its use has continued to increase and we continue to refine the process to identify who may be eligible. So, I wanted to thank a large group of people. Hopefully there are uh uh captured everyone here. Thank you. >> [music] [music]