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Neeraj Agarwal: Hi. My name is Dr. Neeraj Agarwal. I’m a professor of medicine and director of the Genitourinary Oncology program at the Huntsman Cancer Institute at the University of Utah.

Today, I’m very pleased to welcome Dr. Stacy Loeb, who is a professor in urology at New York University, and who presented these innovative data at the ASCO GU Symposium in 2025. So we’ll be talking to Dr. Loeb about this project first and these findings, and how does it imply to our practitioners not only in the US, but across the world. So welcome, Stacy.

Stacy Loeb: Great. Thank you so much for the opportunity to share our findings. This study was specifically about the barriers and facilitators to first-line treatment intensification in metastatic castration-sensitive prostate cancer. And here, we were specifically looking at a sub-analysis based on practice setting and intensification frequency.

So the objectives of this study, first and foremost, were just to identify any differences in barriers and facilitators to treatment intensification, first of all, between the academic and non-academic settings, but also between high and low intensifiers—that is, physicians who are using first-line treatment intensification for more than half of those patients, and then compared to those who are not. And then secondarily, we also wanted to prioritize these barriers and facilitators in order to actually identify potential resources to increase guideline-concordant treatment intensification.

So this is just a schematic of the study. And there were really two phases here. In phase 1, this was really a qualitative design where we conducted these double-blind, semi-structured interviews with US oncologists and urologists.

Now, the interviews were guided by the Theoretical Domains Framework, which is from implementation science. And the themes from the interviews were coded around this framework to really identify what are the barriers and facilitators to treatment intensification in practice.

Then the second phase was really quantitative. This actually involved a discrete choice experiment with more than 300 US oncologists and urologists. And the goal here was really to identify different sets of resources that they think would be most helpful in order to aid in treatment intensification in practice.

So in terms of this first part, the qualitative component, and really looking at the barriers and facilitators in different settings, you can see that the academic setting really had more facilitators than barriers, particularly anticipated regret over losing the best chance at improving survival if you did not do treatment intensification upfront—also, having good clinical support and comfort in managing treatment intensification—whereas in the non-academic setting, there were more barriers, including anticipated regret over side effects and negative quality of life impacts, the cost, and insufficient clinical support. But there were also some facilitators in non-academic settings if they had good administrative support, a habit of intensifying first line, or belief in the urologist’s role in treatment intensification.

We also looked at differences in these barriers and facilitators between the high and low intensifiers. Not surprisingly, high intensifiers mentioned fewer barriers and more facilitators, which likely explains how they came to this point. But still, some barriers, even for the high intensifiers, included cost and if urologists hung on to the patient too long, whereas the strongest facilitators were things like having good clinical support, anticipated regret over losing the best chance at improving survival, good clinical trial knowledge, tendency not to limit intensification based on age and performance status, and a habit of intensifying first line.

Now, for the low intensifiers, main barriers included knowledge gaps, a tendency to intensify second line, and use of treatment intensification first line only in severe disease, and numerous others, including their peer environment and insufficient support. But it was a facilitator if they felt that there was good collaboration between urologists and oncologists.

And lastly, we looked at what kinds of resources would be most helpful across all of these different settings, just in order to figure out what can we do about this because treatment intensification is not happening often enough. And what would provide the best support to these different physicians in different settings and with different practice patterns? And you can see here that across all these groups, decision support tools and databases of post-treatment options had the highest ratings, followed by summaries of clinical trial data.

So in conclusion, there were some differences in terms of barriers and facilitators between academic and non-academic physicians, and also between those who are and are not currently intensifying. But the good news is that we did identify some possible resources that could help. And in particular, these include decision support tools and databases of post-treatment options that could help any of these groups to improve guideline-concordant care.

Neeraj Agarwal: Thank you, Stacy, for such a wonderful presentation of the data. Just for our viewers, I’d like to give some background on why the study was taken. So would you like to just tell us why the study was done in this implementation science domain?

Stacy Loeb: For sure. So the thing is that just like we see a lot through clinical medicine, we have the guidelines. But then, unfortunately, we see a lot of guideline-discordant care or insufficient uptake of guideline-concordant care. And in this case, the guidelines do support upfront combination therapy or treatment intensification. And so therefore, it is critical to determine why this isn’t happening. What are the barriers and facilitators to doing this in real-world practice?

And then implementation science is really focused on what we can do now to address these barriers. And so that’s where this study came in—what are the problems? Why is this not happening? Why aren’t people following the guidelines? And what resources could we put out there that could help to improve guideline-concordant care for this patient population?

Neeraj Agarwal: There seems to be a big disconnect between the clinical trial results from big phase III trials, which almost immediately get FDA approved and then incorporated into guidelines, but then we don’t see the data being applied to real-world patients out there.

So many patients are not getting—well, let’s say many patients are not getting these novel agents, which are really no longer novel. For example, docetaxel chemotherapy was approved in 2014 based on the CHAARTED study, and treatment intensification with docetaxel was present in only 10% of patients with metastatic hormone-sensitive prostate cancer across multiple studies reported.

Abiraterone was approved in 2017. Apalutamide and enzalutamide were approved in 2019. And in studies reported in 2022, to the best of my knowledge, the last studies reported in 2022 and ’23 showed less than 50% of our patients with mHSPC getting these therapies.

And that’s why you are trying to figure out why these physicians who are using these therapies versus not using these therapies in a majority of their patients—what are the basic differences? And what can be done to alleviate those issues so that they can apply this level 1 evidence to all patients? Is that a correct summary, Stacy?

Stacy Loeb: Yeah, absolutely. This is a common problem. But it is really serious. If the data are there and the evidence is not being used, then we really need to understand why and what can we do to make this better.

Neeraj Agarwal: So looking at both phase I and phase II of the IMPLEMENT study, what is the most important roadblock, if you will, which is experienced by, obviously, both sides—academic, non-academic; high intensifiers, low intensifiers? Only difference is it is more of an issue in the non-academic setting and among low intensifiers. But I think knowledge gap, lack of awareness of the data, seems to be standing out among all those factors. Could you please elaborate on that?

Stacy Loeb: Well, I think it’s challenging. There is just so much new data coming out all the time. And it’s great news for the field and for our patients that there are so many more options available today than in past decades. So we are able to extend life in more ways than we previously had.

So while all of this is amazing news, it is very difficult to keep up. And so that is why things like decision support tools or clinical trial summaries really came out in this analysis as tools that could be helpful for use in daily clinical practice.

Neeraj Agarwal: I found one of the factors quite intriguing—when many physicians want to keep the first-line therapy to be used in the castration-resistant setting because they are afraid they will not have anything to use in the CRPC setting, when multiple phase III trials have already shown a huge difference in median overall survival based on when a given ARPI is used in the hormone-sensitive setting versus the CRPC setting. We are talking about a 30% to 40% reduction in risk of death. And still, many of our colleagues are keeping these for later use. And I personally think this is lack of awareness of the evidence out there.

So what do you suggest, going beyond this abstract? What would you suggest we should be doing as a community, other than these videos, for example, to make our colleagues aware? They are very busy clinicians or surgeons, right? They may not have time to go to ASCO or ASCO GU or many other meetings, which take a substantial amount of time, effort, and energy to attend. What can we do to address this knowledge gap among our peers in the community?

Stacy Loeb: First of all, congratulations to you and UroToday for your efforts in addressing this because I definitely think that videos like this and platforms like UroToday are really essential. This is where practicing physicians are looking for quick snippets and hearing from key opinion leaders like yourself on just how important this is. And that this really improves survival for patients is just so important.

There are some initiatives going on in the patient space, too, with more discussions about this among patient support groups. And informed patients can ask their treating physicians about combination therapy or treatment intensification approaches.

So I do think that really a multi-pronged approach—this study that we’re talking about today was really focused on the physician side of things and some of the tools that could help practicing clinicians. But definitely, the patients and their families are another important component. And I do think there are definitely options on that front as well.

Neeraj Agarwal: Those are great points. So Stacy, thank you so much for taking the time today to talk about the IMPLEMENT study, the data, and the potential implications for our patients. I think I really like the last statement you made—empowering our patients, in addition to providing or sharing the knowledge with our colleagues out there, are equally important factors.

So patients ought to be able to ask, “What are the options for me? And what should I be using to benefit myself the most?” And I think the more patients are aware of the data, the more likely they are going to be receiving this level 1 evidence care. So thank you very much.

Stacy Loeb: Thank you so much for having me.