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Alicia Morgans: Hi and welcome to UroToday and our online medical education program Beyond Androgen Blockade to New Pathways and Novel Treatments in Metastatic Hormone-Sensitive Prostate Cancer and Metastatic Castration-Resistant Prostate Cancer. My name is Alicia Morgans, and I have the honor to moderate today's discussion following a presentation by Dr. Robert Dreicer. The topic is multidisciplinary approach in the treatment of metastatic prostate cancer. Thank you so much, Dr. Dreicer.

Robert Dreicer: Thank you, Dr. Morgans. My appreciation for the opportunity to chat. So let's kick this off by thinking about where we've come. It reflects on how old I'm getting then. 23 years ago, the good Dr. Howard Scher and colleagues from Memorial Sloan Kettering first published what was called the Clinical States Model of Prostate Cancer. And just to remind us that when we think about interdisciplinary care, back in the day, prostate cancer was managed by our urologic colleagues with some radiation oncology help.

Medical oncologists tended to get involved as the disease became frankly castrate resistant. We obviously used older terms then. But to give you a sense of the complexity of the disease, this is a modern version of the clinical states model. You can think about this in a lot of different ways. But the reality is is that as we understand the disease biology, as PSA and its clinical state became important, the complexity of management increased.

And one of the things that's a repeated theme in advanced prostate cancer management is that unlike breast cancer or colorectal cancer or lung cancer where sequential therapeutics were built upon prior studies, we don't have that in advanced prostate cancer. There are a lot of approaches and there are a lot of evidence supported ways to treat the disease, but there's almost no comparative data. So one of the things that become very important is to understand that there's not always a right way to do things.

There may be better ways to do things, so you have to keep that in mind. So one of the things about prostate cancer that's very unique is that advanced disease is managed by a very wide spectrum of clinicians. We have colleagues in the community who practice both urology or medical oncology. There are large urology group practices, many of which have advanced prostate cancer clinics, manned and womened by experts in the disease who basically take care of patients all the way through the disease.
If you're a medical oncologist in a community near a large urology group practice, you may not see a lot of advanced prostate cancer. And alternatively, if you're not, you see more. And then certainly there are academic urologic medical oncologists and some of our radiation oncologists obviously have involvement in advanced disease. We know that local disease symptoms is a very common problem throughout the disease continuum. No matter who's managing a patient, local disease symptoms, which requires urologic expertise, is almost always going to be an issue and need intervention.

Androgen deprivation therapy intensification, the really groundbreaking changes that started more than a decade ago with the CHAARTED study and then subsequent multiple studies leading to a really dramatic improvement in survival. Remember, in metastatic castrate-resistant disease, the median improvement in survival from all of our approved drugs is two to five months. Here with intensification, you move the needle sometimes in years. This slide adopted from the good Dr. Fizazi looks at de novo high volume patients and shows you sequential improvement in outcomes.

So a really important moving the needle exercise in patient outcomes. However, the next slide will show us some complexity. So this is just one in a sense real life version of what happens in the real world. This work by Dr. Freedland and colleagues from the VA, right? So economic issues are not the issue because it's for all comers. Look at the bottom bullet point. ADT plus intensification happened in... Two-thirds of the patients are not getting treated. And there are other real world examples of this.

And one of the things that people ask all the time is, okay, let's say... What's wrong with this picture? We have a therapy data-driven level one evidence that improves survival by years and most people don't get it. So why is that. And there's lots of different reasons some people can't get it. But when you're talking about two-thirds or more of people who don't get it, there's got to be another reason. And one of the reasons likely is that because of the heterogeneity of the practitioners involved and the level of involvement in terms of experience will vary from clinician to clinician.

Where interdisciplinary care, tumor boards, conversations about disease management will frequently overcome some of this, the absence is also a problem. Next generation imaging, probably not next generation anymore. PSMA PET/CT is a standard of care. It's approved in the assessment of biochemical failure, high risk patients with localized disease, and obviously to, in a sense, qualify a patient to receive Lutetium 617. And over time, this will become broadly used throughout the disease construct.

We all recognize that when you start using more sensitive imaging, what you find is disease sometimes that you didn't expect. And one of the things that many of my colleagues have written about and thought about is when you find things earlier than you should or maybe than you used to do, you do more to patients or less, right? The disease is worse than I thought. Oh, I'm going to change what I do. Or, oh, I see more, so I'm going to do more. And we don't know what the right answers are because the prospective evidence to support what we do is not yet there.

This is another reason that interdisciplinary discussions are absolutely critical because we don't know what the right answer is, so we need to develop a consensus. One other aspect of managing this disease is the role of genetic testing. We know that 15, 20% of patients will have some potentially actionable DNA damage repair mutation or other findings that impact on therapeutics, MSI high status, tumor mutational burden, et cetera.

We also recognize that genetic testing happens in a very small subsets of patients, despite the fact that every society guideline, all of our urologic colleagues, all of the medical oncology societies clearly indicate the need for at least germline testing at the setting of metastatic disease and increasingly the role of somatic testing. We also recognize it's not happening. So just to try to begin to put this in perspective, lots of different clinicians involved in care.

Historically, our radiation oncology colleagues and our urologic colleagues have had very close interdisciplinary relationships which continue to this day. It's a little bit more complex when you start adding medical oncology into the group. Because you have a variety of different clinicians involved and there's not level one evidence for sequence, what happens is if you only have certain things in your toolbox, you're only going to discuss certain things.

And one of the things about this disease, castrate resistant metastatic prostate cancer, castrate sensitive metastatic prostate cancer are incurable diseases for which therapy can improve survival, and our goals of care are improve survival, maintain quality of life. When you don't have level one sequence evidence and you don't use all the tools in the toolbox, likely we are causing some patients to probably have, if not substandard care, not optimal care.

The introduction of more toxic regimens, even things like PARP inhibitors, which are sometimes challenging drugs, if you don't do genetic testing, well, you're not going to know whether or not a patient may be a candidate for a PARP. And if you're going to use a PARP and it's a toxic drug, would it not be better to use it earlier in the disease when the data was derived? So there are lots of these issues that speak to how much we talk to each other, being aware of therapeutic options.

And again, as you move next generation imaging, genetics, all of these things require competencies being able to remain state-of-the-art in terms of care, and it depends on how often you see the disease that leads to some level of clinical expertise. So very heterogeneous disease, very heterogeneous caregiver group. We've talked about the impact of next generation imaging. Remember, leftward movement, as we intensify, we basically change the kinds of next therapies that are required.

And if you don't intensify, basically you're looking at different groups of patients. You need to be able to recognize, right? There's not a standard sequence of therapy because when somebody gets to MCRPC, they may look very different if they've had intensified therapy or not. And I think I would just close by saying that the optimal management of patients with advanced prostate cancer is not specialty dependent, but it is expertise dependent. Appreciate the opportunity to spend a few minutes today. Thank you.

Alicia Morgans: Thank you so much for that presentation, Dr. Dreicer. What a wonderful way to put an extremely complex workflow into context. So thank you for that. As we're thinking about intensifying treatment, as we're moving therapies earlier and earlier in the disease state, multidisciplinary care is so critical. And you mentioned that we're really underutilizing the intensification strategies that we have. Do you have ideas about how we as a community can work together to improve on these deficiencies?

Robert Dreicer: Well, one of the things that I would point out not to be self-serving is is that exactly what we're doing here. I mean, continuing medical education is absolutely critical, right? I mean, it's the fusion of knowledge. And unfortunately today, our colleagues, wherever they are, a extremely busy. So education, letting people know what the data is. This is not a new problem. We're aware of other examples in urologic oncology, the lack of neoadjuvant therapy in muscle invasive bladder cancer.

There are lots of examples of good data not being taken up. But this is really, really good data. One of the other things that I think is critical is education of patients. If a patient understands that there may be more to it than just X, they ask their clinician, "Hey, doc, how about maybe getting somebody else's thought about this, or I want a team together."

So clinician education, which is a slow laborious process, but you take one doc at a time and try to improve his or her understanding of the disease state and really reminding patients that it is an interdisciplinary disease and patients will probably be better served if they've got a team working for them.

Alicia Morgans: I think that's a great message. And also just curious, you mentioned if we're going to intensify, we get more bang for our buck. We have a maybe better patient fitness if we do these treatment intensifications earlier on in the disease process. Can you speak a little bit more to that?

Robert Dreicer: Yeah. I mean, there's no question that... And I think the PARPs are a perfect example, right? I mean, we know that we have an agent that's approved in patients who progressed on an ARI. So if that patient has either gotten an ARI as their first treatment for MCRPC or got it as part of intensification and there's a BRCA2 mutation, PARPs are oral cytotoxics, right? They cause fatigue and myelosuppression. Our average patient is 68 to 70 years old, has some other medical problems.

Now, if we want the PARP to have the best chance of helping the patient, they've got to tolerate it. So using it as an end of the line therapy makes no sense. So the reality is if you know the evidence that led to drug approvals and you know the population that you're dealing with, using therapies at the most optimal time. It's not to say that using it later is wrong, but it may be more optimal to use it when people can tolerate it better. That's the kind of conversation that comes because most of our community urology colleagues don't give PARP inhibitors.

So the point is is that maybe if there was greater awareness or there was a team effort to say, hey, we know this patient has a mutation, there are therapies, and it may be better to use it somewhat earlier in the disease. So again, it's just effective communication, trying to come up with an optimal plan in the absence of being able to say, "This is what you do now. This is what you do later."

Alicia Morgans: That makes a lot of sense too. So I'm wondering, as you're thinking about side effects, and you mentioned some associated with PARPs, but of course, we have side effects associated with all of our systemic therapies, what is your strategy in terms of trying to proactively share those side effects with patients, with clinicians who are new to using these strategies so that they can feel more comfortable and confident trying these treatments?

Robert Dreicer: With patient education, as we all know, I mean, look, it starts with T suppression, right? Many of us spend a lot of time talking about the nuts and bolts of metabolic changes because they're so impactful on our patients. So patient education is absolutely critical and having patients know what they might have to expect. It's a little harder with some of our colleagues simply because in an individual basis, being able to communicate side effect profiles to clinicians is challenging.

And that's where education comes in. And frankly, even if it's... In today's world, you take one doc at a time. If you hopefully can bring some information that will enlighten him or her about maybe a therapy that they don't use very often or may be able to say, "I don't give this therapy, but my colleague does. This is what I've been told to expect," I mean, setting the stage.
Because you and I both know our urologic colleagues really have enormous trust from our patients and enlisting them in being able to provide support and education and preparation for our patients increases the chance that the patient is going to show up, get the consultation, actually hear about therapy options.

Alicia Morgans: Absolutely. I want to just thank you again for sharing your thoughts and your expertise. Any final comments before we close?

Robert Dreicer: I would just emphasize the last issue. I mean, again, historically, there's been a lot of give and take about a lot of stuff. There are a lot of our colleagues who are experts in managing advanced prostate cancer. Some of them are urologists. Some of them are medical oncologists. And the reality is that to me is not the issue. The issue is if you're going to... In a sense, if you break it, you own it. So I think our colleagues need to be brought up to speed if you're going to manage this disease state to do it optimally.

Alicia Morgans: Absolutely. Well, thank you again, and we really appreciate your time and your expertise today.

Robert Dreicer: Thanks for the opportunity.