Read the Full Video Transcript

Neeraj Agarwal: Hi. My name is Dr. Neeraj Agarwal, and I'm here today with Dr. Martin Schoen from the St. Louis VA hospital and Dr. Bruce Montgomery from the Puget Sound VA hospital. Here we are going to talk about the exciting study on treatments and outcomes of patients with metastatic hormone-sensitive prostate cancer in the VA hospital. Marty, would you like to tell us about the study you and Bruce both have conducted? And congratulations, by the way, on this study.

Martin Schoen: Great. Thank you very much, Dr. Agarwal. Yes, I'd like to discuss the outcomes and the treatments of metastatic hormone-sensitive prostate cancer in US veterans. Well, thank you very much for giving me the opportunity to discuss our work. I'm Dr. Martin Schoen at the St. Louis VA Medical Center, and I'm accompanied by Dr. Bruce Montgomery from the VA Puget Sound. We're going to be talking about treatment and outcomes of metastatic hormone-sensitive cancer in US veterans.

And we're going to talk a little bit about how veterans are treated, what is the survival in a veteran population as well as a US population, what is the change in combination therapy that has occurred over time in the VA, as well as has it affected overall survival, especially with combination therapy versus ADT monotherapy? And lastly, we will look at the comparison of combination therapies and overall survival. I would like to highlight that all of the patients that we discuss are de novo metastatic hormone-sensitive prostate cancer, or metastatic mHSPC.

So to give an overall view of the US veterans compared to other patients with metastatic hormone-sensitive prostate cancer, we compared the overall survival for the last 20 years using VA data compared to SEER, which is the Surveillance, Epidemiology, and End Results database that consists of patients across the US. And we highlight that across all groups of patients, from patients that are in their 50s and 60s, as well as 70s and 80s, that survival has been improving in the last 20 years, and it's likely because of some of the new therapies.

And when we look at the comparison between SEER and the VA, we also see that the survival of patients treated within the VA, which is the light blue dots, is higher or longer at every time point, and at every age group, than the patients that are in the SEER registry. And it's most dramatic in our youngest patients, or patients less than 70, where we can see that survival has improved from approximately 30 months in 2000 to 2004, up into the 40 to 50 months in—sorry, 2015 to 2019.

And this is likely due to some of the changes in treatments that have occurred over the last 20 years. And we decided to focus on patients treated within the VA in the last 10 years to document how the new treatments have been able to be implemented in the VA. So we looked at patients with de novo metastatic hormone-sensitive prostate cancer and described their treatments within four months of their initial ADT. As you can see, in 2013, almost all patients were treated with ADT monotherapy. But over time, from 2014 to 2016, the use of docetaxel increased and hit almost 20% in 2016.

And then when we get to 2017, this is when the new RP agents, or androgen receptor pathway inhibitors, began to be used in metastatic hormone-sensitive disease. And in the orange bars, you can see that has increased since 2017, and in 2023, which is the most recent data that we have available, almost 60% of patients are receiving an RP and another 10% of patients received docetaxel. So that combination therapy is given in approximately 70% of patients within the VA.

And what are the outcomes of this? Well, we see that during this period of time, the outcomes have—we already know that their survival is improving. But we wanted to compare the different treatments, whether it's ADT monotherapy, which is the traditional treatment, to the combination therapy. And we see that combination therapy is associated with a longer survival in this real-world population. The monotherapy arm had a survival of about 32.9 months, and the combination arm was 40 months with RP and 38 months with docetaxel.

I would like to highlight that the age of the population was different between these groups. The ADT monotherapy patients were older, approximately 75 years old. The patients receiving RP were about 73 years old, and the docetaxel patients were the youngest with a mean age of 66. But it does highlight that the improvements from the clinical trials seem to be translating to longer survival in the real world.

And the last thing that I wanted to highlight is there's always been a question about the volume of disease, or really the amount of cancer that a patient has, and there are ways to measure the amount of cancer based on the Charted criteria. And what we look at on the left is that we took patients that all had high volume, high Charted criteria. So this is a sub-population of the entire group, approximately 1,000 patients. And we see that overall, the patients have a survival of about 32 to 33 months. And in these patients who received combination therapy, either docetaxel combinations or RP combinations, there was no difference in overall survival between each type of doublet combination.

You can see on the right-hand figure this is the low-volume patients, which have a much longer survival and better prognosis. The overall survival was 64 to 67 months with either docetaxel or RP as well. There was no association with survival between the docetaxel or RP arms in the low-volume group, but they did have a much longer time until death.

So in summary, the veterans with de novo metastatic hormone-sensitive prostate cancer have equivalent or longer survival than the general US population, and survival is improving across all groups in the United States. We also know that combination therapy for metastatic hormone-sensitive prostate cancer is being adopted by the VA, and in 2023, it was used in approximately 70% of our patients. And then we also know that combination therapy is associated with a longer survival based on our data, and it's also provided more commonly to younger patients.

And then the last thing is we did not see any differences in overall survival based on the type of combination therapy that was provided, either an RP-based combination or docetaxel. Thank you so much for allowing us to discuss this work, using the Veterans data to understand real-world treatment and outcomes in metastatic hormone-sensitive prostate cancer.

Neeraj Agarwal: These are great data indeed. And congratulations again to both of you. Let me ask a question for Dr. Montgomery. So Bruce, it is great that survival outcomes appear to be longer in prostate cancer patients in the VA hospital, especially in the younger veterans. Any thoughts on why this is occurring in the VA hospital?

Bruce Montgomery: Yeah, great. Thanks for the question. Again, thanks to you and UroToday for giving us the opportunity to present today. So I think a couple of things are worthwhile emphasizing in addition to your question. So one of them is this real-world evidence, which is becoming very popular out there in the community, is really important, particularly for an integrated health care system like the VA. So we are the largest integrated health care system in the United States. We can implement changes depending on how we're doing. And these data tell us how we're practicing.

So that, for example, if we see there's a deficit—for example, if we were not giving combination therapy in the kind of frequency that we would like to be seeing it—we should be changing the approach. Education of providers, education of patients, etc. The other thing is it helps us to figure out whether our patients are responding in a way that clinical trial patients do, for example. I mean, those are patients who, in many cases, are excellent performance status. Generally, they are just in a better position to benefit than real-world patients, let's just say.

So I think from the standpoint of your question, which is why do the VA patients seem to be doing better, particularly in the younger age group, I think the VA is an equal-access system. There are no financial constraints about access to medications depending on socioeconomic class or whatever. And as I think we know, when patients aren't at the age of having access to Medicare, your ability to pay for medications in particular can be problematic outside of a system where they're being provided equally to everyone.

So I would say that some of that may be playing a role in the better outcomes that we're seeing. I would also say that the VA system is pretty good in terms of uptake of the kind of approaches that we've been discussing for reasons that Dr. Schoen has pointed out to me on multiple occasions. And that is, part of it is we're all associated with academic medical centers where the expectations are higher. Secondly, as part of that, we're all educating the next generation of physicians, and we want to be representing well, shall we say, and providing care that is in line with level 1 evidence. And so I think it would be very hard for me to say exactly what's going on there, but those would be my thoughts about why the patients in the VA are doing better.

Neeraj Agarwal: Thank you, Bruce. These are indeed wonderful data. Marty, can you discuss how this information is different or similar to others?

Martin Schoen: Yes, definitely. The data that we collected or started with was using the VA Central Cancer Registry. So all of the patients had to be in our cancer registry, which means they were enrolled in the VA and had a diagnosis and staging within the VA. And so therefore, we know their stage with really good reliability. And that is different than some other methods that may use things like ICD codes or other data sources. By using the registry, that really does increase our reliability.

As well, we also use a narrow window compared to sometimes it's other use that would be similar to a clinical trial. So most of the clinical trials, such as Charted or Latitude, would only allow 90 to 120 days before starting that second agent. And so we mirrored that window in our analysis. And so therefore, we feel that we have a very robust method of both detecting the metastatic disease as well as the treatments.

Neeraj Agarwal: So the adoption of the combination therapy in the VA, even during the COVID-19 pandemic, is impressive. Any thoughts—and I know Bruce did discuss some of this—but any thoughts on how the VA has been so successful?

Martin Schoen: I think that it's because we really have a team approach to both learning as well as delivery of care. As mentioned, we are commonly affiliated with academic medical centers where we have experts in the field, but we also have our clinical pharmacists available, as well as other team members from nuclear medicine and radiation oncology that are integrated into our care patterns. And I think that sort of multidisciplinary care, as well as the latest science, really helps us to be able to implement our new therapies a little faster.

As well, we do have pathways that are created by the oncology program that is across the entire nation, where it gives us guidelines and guidance in what treatments should be standard in specific situations. So I think all of that structure really helps us to implement and disseminate the treatments at a faster pace.

Neeraj Agarwal: Thank you for elaborating on that. Bruce, any comment on your collaboration with the PCF and how it could have impacted?

Bruce Montgomery: Yeah, thanks for the opportunity to talk about that. So for those of you out there that haven't heard about this before, the Prostate Cancer Foundation has entered into a collaboration and has been providing a great deal of research support for the VA, specifically in prostate cancer research now for the past five years. And as a result, this collaboration has resulted in the setting up of a network of VA centers focused primarily on things like sequencing precision. And I would say there are a number of publications about this that suggest that in the VA, we're actually doing somewhat better than the greater community in terms of providing the kind of germline and somatic sequencing that really informs a lot of precision care that we all want patients to have access to today.

But the idea being that the PCF collaboration and their investment in VA research has been really quite remarkable. It has led to a number of research studies; it's now led to the setup of a precision oncology network across all histologies in the VA. And so the VA–PCF collaboration, and particularly the PCF investment, has really led to a lot of things, not the least of which is Dr. Schoen's work that we discussed today, bringing in new investigators, bringing people to using VA, as we call it, real-world evidence or data.

And it is worth emphasizing that Dr. Schoen just sort of raced over that data about high volume versus low volume. But I think we all know that in a clinical trial you can extract that data sort of prospectively. When you're doing it out there in the big wide world, the amount of energy to extract that data is pretty remarkable. So the data that you saw presented is more granular than essentially anything you could get anywhere else outside of a clinical trial. So those are aspects of the VA–PCF collaboration, which is supporting Dr. Schoen as a PCF Young Investigator to do this sort of work, that has really been beneficial to the VA, and I think for veterans and care of prostate cancer in general.

Neeraj Agarwal: I'd like to hear that from Marty also. So Marty, this information presented is quite rich and unique. And how have you been able to acquire such wonderful data that can help inform clinical practice and maybe the design of future clinical trials?

Martin Schoen: Yeah, so I've been able to have wonderful mentors, including Dr. Montgomery, but then a network of people that I am able to collaborate with and then build upon prior resources. Several years ago, a prostate cancer data core was created as a result of a Prostate Cancer Foundation collaboration, allowing us to start with a number of patients that we have prostate cancer and that we have certain treatments. From there, we were able to build an even more robust database that gives us the exact timing of every treatment, as well as every imaging study that was performed.

And because the VA is a comprehensive network where we have all of the data available, we have the ability to look through every imaging study, from PSMA PET scans to nuclear medicine bone scans, and CT scans, and review those scans to be able to estimate what the volume of disease would be if it was done by a clinical trial. And that data, combined with things like PSA and comorbidities and other medicines, really gives us information about veterans that hopefully we will use to design new trials to be able to personalize the therapy. Patients that have wonderful responses—maybe we can possibly de-escalate or make that therapy intermittent. Or patients that maybe do not achieve the milestones that we would like, be able to offer them additional therapies that are going to be coming down the road in new clinical trials.

Neeraj Agarwal: And we are really hoping that the VA has set this example for all of us to follow in the real world out there, as we know that implementation of level 1 evidence has been quite slow in our real-world patients beyond the VA hospital. And there are multiple new trials which are coming up, they will be reporting next year or in the near future, and I'm really hoping that we will continue to set the example for all of us. Any last words, Bruce, Marty, for our audience?

Bruce Montgomery: Yeah. So I wanted to actually call out the fact that some of this work that we've been discussing really is informed by the work that you've been doing as well. You've been very good at telling us why people are not taking up combination therapies when they should be, which helps all of us to better inform how we practice out there in the big wide world. And I think just re-emphasizing that the VA does represent a resource for other investigators. We're always interested in collaboration. And so always think about the VA when you're thinking about big data.

Martin Schoen: Yes. No, I appreciate the opportunity to talk about our work. And I definitely thought, Dr. Agarwal, your work with the Libertas study and others have really helped us to advance our thoughts about the care of prostate cancer. And it's just wonderful to be able to have such a team approach where investigators from around the world, as well as academic centers, and then also in the VA, are able to get together and to use the latest science to really advance the care. And the advances that have happened in maybe the last five years are probably even much more than the prior decades before that, because of this ability to communicate, to be able to use the latest techniques, and be able to implement the best science that we have available. Thank you.

Neeraj Agarwal: Thank you to both of you for joining us today.