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Neal Shore: Well, hi, everybody, and welcome to our program today. It's a series of different topics and different speakers. The project is called Interdisciplinary Management for Patients with Prostate Cancer. Super pleased to have my good friend and colleague, Paul Sieber. Paul has been a longstanding researcher and educator and expert as a uro-oncologist in prostate cancer. And there are so many new things that have happened along the way, and he's going to address today the risk stratification for patients who still have hormone-sensitive or castration-sensitive disease and how much the world has changed since he and I finished our training. Paul, please go ahead.

Paul Sieber: Yeah, so my task today is to talk about the world, I guess, as I see it these days, Neal, and how it's changed in the many decades since we finished, and what a multidisciplinary approach is necessary just in managing prostate cancer patients in general, but certainly the advanced prostate cancer patient, all the challenges that he brings when he walks in the door, and what it's like in 2024. So if you look today at what we see walking in the door, clearly across the country, everyone's seeing more advanced cancer presentation. And I think that's probably a tribute to the lack of screening from USPSTF guidelines, which at least in my locale has made a big change in terms of high-grade disease and metastatic disease presentation, which leads to the first thing that comes out the door these days is genomics and how it's taking off.

Just a few years ago, we started, introduced the idea of adding genomics to an assessment of a patient walking in the door, and pretty much it was centered specifically on the patient with metastatic disease. And now we're moving to earlier and earlier in the disease to think about a genomics profile to assess what you're going to do. And so even intermediate patients are frequently being screened, and now we're even moving forward to low-risk patients being screened. So it's a big change just from the fact that genomics is readily available and the cost has come down. And then when you move on, just thinking about if you're going to even treat a patient, the idea of dual therapy treatments and triple therapy treatments and involving medical oncology, trying to have an opinion about what you're going to do with that really advanced patient when he walks in the door, whether he is going to have treatment for metastatic disease or even high-risk localized disease.

And then the latest hot topic is sitting down and saying, "Hey, maybe we're doing something bad from the standpoint of cardiovascular morbidity and two steps forward to treat his prostate cancer and one step backward, or one giant step backward because we didn't address his potential cardiovascular risks when we're adding our therapies." So even the man who walks in the door these days who doesn't have metastatic disease, so you're thinking, "I can manage this on my own," well, I think the first step for most of these guys is they have to think about a genomics profile to at least aid somewhat, not only in future management but maybe even risk stratification going forward. And that may not be something that you're familiar with. So first, you're going to have to think about, "Do I have to extend my reach to talk to somebody who has expertise in genomics in my area, or at least someone across the country I can reach out to get advice about if I've done a genomic profile, how do I interpret what I've got here in terms of this information?"

And the next thing that comes up, especially when you look at the NCCN guidelines these days, is life expectancy. When you come to various points along the curve, whether the man has a five-year or 10- or 15-year life expectancy, to come up with a treatment plan. So that is not such a simple task, and it may require you reaching out to your primary care physician, or he or she may not also feel comfortable trying to opine about what's the status of this patient. And probably the next most likely thing is probably reaching out to his cardiologist if he has cardiac problems because cardiology is a big deal in terms of the risks of drugs we're giving them or even understanding what's going forward. And I think today as well, we're used to the old-fashioned, "Hey, we also need to involve a radiation oncologist because that's something even back 30 years ago, does this man warrant surgery or does he warrant radiation?

I think that conversation has been there for a long time, but as much as these days we're looking at primary treatment, we're also thinking about people even with metastatic disease to involve not only our potential medical oncologists but our radiation oncologist as well because a lot of people who are coming in with high-risk disease are going to require an opinion about what to do with more aggressive potential dual therapy for radiation therapy alone. And I think now it's even easier when the metastatic patient says, "Everybody universally needs genomics." And I think if you can't understand that going back again, who in your area can help you interpret what the genomics means, and it's becoming more and more complex. They say BRCA abnormalities are changing at the rate of one new one a week, basically, to add to the pool of what's BRCA positive, just to look at that specific abnormality, which is the commonest homologous replication repair defect we see in patients with prostate cancer.

And I think life expectancy's a bigger and bigger deal because, again, when we look at these people with metastatic disease, they're living a longer time, but even understanding what the expectations are in terms of how long they're going to live with their other disease problems and how you get cardiology involved to say, "Hey, we may be increasing that risk." I think medical oncology now we may look at, "Hey, maybe this patient is ideal for dual therapy, but you still need an opinion about maybe we need to consider triple therapy." And I think that's certainly something that's widely underused these days. I think the whole idea of radiation oncology for just localized disease is now passé because we're thinking about radiation oncology from the start, particularly with those patients with oligometastatic disease. So I think there's a host of people that are now suddenly part of this team.

So what I think about prostate cancer today and someone walking in the door and think about the little vacuum of me operating by myself 30 years ago or maybe involving my radiation oncologist, I'm thinking these days, "Gee, I probably need more input from someone who's managed the patient, whether it's his primary care physician or many times maybe fallen into cardiology." I need my radiation oncologist for many aspects of the disease, not just treating localized disease. I think medical oncology has more to offer these days in terms of multiple options that you may not be familiar with or not comfortable managing, so they have a new role to play. Genomics means you need to have some type of genetics expert out there. I think the biggest deal for urologists these days is who's going to be the captain of your ship? Because there are multiple people that are going to be on that team.

I think when you start to say, "We're involving four or five people," I think hopefully the urologists will be that captain of the ship to say, "I have some idea of what's going across all these people's thought processes in terms of managing the patient." But someone has to put it together for the patient to say, "How am I going to manage that new patient walking in the door?" There's more decision-making than just, "Should I have this prostate surgically removed?" What other things need to come into play when you're trying to manage that patient? So that's kind of a quick run-through of why I think the multidisciplinary world of prostate cancer is dramatically different than it was 10 years ago. Your thoughts, Neal?

Neal Shore: Well, Paul, that was a great overview, and you captured so much. I mean, one of the key things I think you said, and when it comes to doing genomic profiling, is it's not if you're going to do it, it's when you are going to start doing it? Because it's been around, and it only continues to amplify what our treatment choices are for patients, and not just in the very advanced CRPC or even the mCSPC patients, sometimes even in high-risk localized patients, patients with, for example, as you said, a BRCA. So I know you've been doing testing for a long time. You do the germline, you do the somatic, you do tissue, you do liquid. And I still think we're dramatically under-utilizing genomic profiling. Your point, which is really where we want to go, is to move towards this precision-based therapy, really not just throw the kitchen sink at everybody, but have a better understanding of their lab parameters, their clinical parameters, their performance status, but now also molecular markers, such as genomic profiling.

And it gets complicated, to your point. I mean cardio-oncologic, neuro-oncologic, all the key disciplines in addition to med oncs and rad oncs and neuros, there are pharmacists and geneticists or genetic counselors and educators. But let me ask you this, Paul, when you talk about the captain of the ship, and there's no one size fits all model, right? And we talk about the heterogeneity of prostate cancer, there's heterogeneity as to how we practice medicine all over the world and certainly within the US, within every state. What are some models that you see that work well and some new things for people to be thinking about in the interdisciplinary way? Because we can't continue to have this old school thing where you just come and see me and if I'm a busy general urologist, I'm going to not offer you all these amazing advances that you've described.

Paul Sieber: Well, I think there are a couple of different ways to try to maybe skin that cat. I mean, I'll pick one thing. I'll pick medical oncology. Two things about medical oncology I found interesting. One is when I talk to key opinion leaders across the country, they all bemoan the fact that they never have genomics because they're missing the original biopsies and tissue. And I go, "Oh, my gosh. It starts with us, when the guy walks in the door." Because we tend to see the patient first. We have the tissue, we have done the biopsies, we've done the radical, we should get that ball rolling earlier in the game. But when it comes to dealing with medical oncology, a couple of models that I see that work well, my medical oncologist, I'm on the phone basically once a week, if not more, basically touching base about how we're going to manage patients, or patients that we share back and forth, and I think that discussion is critical.

I think another model that I've seen work well is when a urology group brings in their own medical oncologist. I mean, you really need that key person that you can reach out to and say, "I'm the guy." And I think that's one of the challenges when you say, "I'm referring a patient to oncology," it's a big darn hole when you send it to an entire group. I think people have to identify that there are 147 cancers in people. There's no one person that could be an expert. And certainly, in my locale, my oncology group that I use has one guy who I can reach out to who's really worked out well for me. Or I found another group down in Alabama that they have their own medical oncologists on board that are specialized in the topic because it's getting so complex, it's more than someone can handle, so I think that interaction's critical.

I would say the same with my radiation oncologist. I would say, I don't necessarily talk to him every week, but I probably talk to him every two weeks. And once again, in my radiation oncology group, it's that dedicated individual. So I think the whole process is becoming so complex, the idea that a urologist can manage all of this by himself in terms of prostate cancer and bladder cancer and kidney cancer and all the complexities, it's getting challenging. I think you have to think about "what can I handle?" I think the day of "I can dabble with this" is done. You need to either recognize, "I'm going to push this further, or I need to find someone in my group to help take over that I can talk to. The same way I've got to find a medical oncologist and a radiation oncologist who are more dedicated to the topic." Because it's just becoming more complex than you can handle.

Neal Shore: Yeah, fully agree. The complexity is great because it's offering us better personalized, precision-based care. And so we're offering patients better outcomes and better quality of life. And maybe we're also improving the health economic outcome systems. Using, for some models, an advanced practice provider, having virtual tumor boards, specializing in just prostate cancer or just bladder or just kidney cancer, working hand in glove, as you say, with interventional radiology colleagues. So you can get biopsies, get the tissue, get it sent early, make sure that it hasn't degraded. But then, of course, all these things that you've talked about, nutrition, exercise, cardio-oncologic issues, patients are demanding it. And if we don't offer this, I think then they'll say, "Well, thanks, Doctor, but I'm going to go to somebody who can offer it."

Paul Sieber: Well, I think you're spot on. In my location, one of the things that my medical oncologist has set up is a formal process with our physical therapy department to have specific people, again, dedicated to patients specifically on androgen deprivation therapy and set up a program for them separate from the typical hip fracture they're seeing or the typical spinal cord injury or something else that they're rehabbing. I mean, they are a unique set of people, and that specialization is absolutely critical.

Neal Shore: Well, Paul, I can't thank you enough. It's been a real great privilege for me to call you my friend and my colleague, and it's been great, you and I together on this journey over these decades, seeing one life-prolonging therapy of docetaxel in 2004, and now we have, I don't know, who knows, up to 14. And not to mention all the advances in genetic testing and other molecular markers and the multidisciplinary... People used to, we'd have internecine warfare. And I think now it's just all about doing what's in the best interest of patients and making our careers and our lives that much more fun and enjoyable in the pursuit of specialization of cancer care. So thank you so much for this program and thanks for everything that you've brought to the field.

Paul Sieber: Hey, great deal. Great chatting with you today. Thank you.