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Zach Klaassen: Hi, I'm Dr. Zach Klaassen. I'm a urologic oncologist at the Georgia Cancer Center, and I'm pleased to be joined for this UroToday discussion on nonmetastatic CRPC with Dr. Zach Reardon, who is a urologist at The Urology Associates in Mobile, Alabama. Zach, thanks so much for joining us today and for your time.

Zach Reardon: Yeah, absolutely, Zach. Thanks for having me.

Zach Klaassen: So today, we're discussing nonmetastatic CRPC, and when you think about this from your clinical perspective and the patients you're seeing in the clinic, how common is this? How many patients are you seeing in a given month with nmCRPC?

Zach Reardon: Sure. So, with nonmetastatic castration-resistant prostate cancer, in my cohort of advanced prostate cancer patients, it isn't necessarily a huge portion. I think that's probably multifactorial, just given some shifts that we were experiencing in terms of imaging modalities, newer treatment indications, and some other things. But I think it's an important number. I think that even though it may not be a huge portion of patients, the early recognition and timely intervention for patients with nonmetastatic castration-resistant prostate cancer is crucial because this represents a fundamental shift in the biology and behavior of their malignancy, signaling a propensity for more rapid progression or adverse outcomes.

So, in my mind, the shift towards hormonal resistance, even if we don't document radiographic metastatic disease, is almost more significant and raises my level of concern more than someone who may present with hormone-naive disease and oligometastatic lesions.

Zach Klaassen: Yeah, absolutely. We know the landmark trials published in 2018, 2019, all phenomenal data, metastasis-free survival, overall survival benefit. When we look at the design, these were all based on conventional imaging and got these patients into the trial. So obviously, we've had the influx of PSMA PET over the last several years. How do you, A, handle the patients that come to you with a PSMA PET with maybe just a very small area that otherwise would be conventionally negative, and how do you counsel those patients? And do you routinely order PSMA PETs for these patients?

Zach Reardon: I guess I'll answer that maybe in a backwards fashion. Where we are, we are trying to adopt PSMA PETs, and I think we've had relatively good success getting those approved in the right patients. I think the question of how do we interpret clinical progression in the setting of newer imaging modalities when compared to studies that were designed around conventional imaging is an important and challenging question. Obviously, there's a constant improvement in technology that usually outpaces the data that's already been published. In my mind, what I try to do is use the best information that I have at hand. If a PSMA PET is positive or documents M1 disease, I err on the side of treating that patient as M1 because in my mind, that's probably going to have more inclusive treatment options available based on that M1 categorization. That's going to maybe give us a little bit more flexibility, a little bit more opportunity to potentially introduce an agent sooner.

We know where their disease pathway is heading at this point, and so I tend not to try to come up with a "fudge factor" for, "Well, this probably wouldn't have been positive on your bone scan." What I do is say, "This is the best information with the best imaging modality we have. We're going to categorize you as an M1 patient and likely treat you that way moving forward." And that being said, I think there are nuances with how we treat patients on an individual basis, taking into account.

Zach Klaassen: Yeah, absolutely. We were talking offline a bit about the size of your practice and advanced providers and nurse practitioners, etc. How do you incorporate them into maybe the follow-up of these patients? Because once they're rolling, these nmCRPC patients, they're pretty easy to manage in the sense of toxicity checks, PSA checks. How do you incorporate the APPs into this management?

Zach Reardon: Yeah, I think you hit the nail on the head that what I would say to folks who may be looking at starting an advanced prostate cancer clinic in their practice or incorporating that is you're absolutely right. Fortunately, these folks, especially the nonmetastatic castration-resistant folks, often feel really good. They're high-performing. Usually in pretty good shape. These aren't going to be folks who are going to take up an insane amount of your time in a clinic setting. It's very appropriate to have a mid-level follow these folks once they're established, so we've done a couple of those things that you talked about.

Usually what we do is we start a patient on a new agent. I like to see them back within a six to eight-week period just to make sure that they're doing okay. Once established, moving forward their med checks and PSA checks, we absolutely fold in APPs to help with that. We've also developed our men's bone health program to be heavily run by mid-levels, and I think that's a really good space for advanced practice providers to assist in an advanced prostate cancer clinic.

Zach Klaassen: Awesome. We touched a little bit on the three previous trials. If you line up these survival curves, they're all very similar, and so when we talk about selecting therapy, there are nuances to it, as we've talked about. Do you focus on PSA doubling time in general when you're looking for an agent? And is there a specific aspect of these agents that you're looking for when you're starting somebody? Maybe side effect profile, drug-drug interactions, etc.?

Zach Reardon: Yeah, so I think obviously a more brisk doubling time is going to lead me more strongly to encourage someone to consider treatment. There are probably several things to take into account. The overall PSA value, so maybe what their prior nadir was based on what treatment they had I think is going to give us a sense of overall shift in their disease process, so that's something that I look at. But if I see someone with a PSA doubling time of less than 10 to 12 months, that's progressing truly above the nadir of wherever their post-treatment or prior PSA was, we're having a strong discussion about starting therapy. I think this is also a space where the utilization of newer imaging modalities comes into play and guides the discussion.

I think certainly performance status is a big thing that we evaluate. Not all patients are the same, just based on what their demographics might look like. So I'm sure you've seen it in your practice, we have guys in their mid-eighties, even nineties that come in and they're golfing and walking every day, and you're going to err on the side of being a little bit more aggressive with them. Someone who may have more limited physiological reserve or poor performance status, I think it's always good to establish a conversation upfront with the patient and family as far as goals of care, balancing cancer outcomes with quality of life and performance status. And I think that sets an important framework for the patient-doctor relationship moving forward and can help guide the discussions about how aggressive do we want to be moving forward.

Zach Klaassen: Yeah. I've often thought, and I say to my residents too, if you're looking to get into the advanced prostate cancer disease space as a urologist, a little outside of the radiation or surgery discussions, I think the M0 CRPC space is a great one to get into because we already have these patients. I'd love to hear your thoughts on that as somebody who's maybe thinking about branching out and moving into a little outside of maybe their usual strike zone.

Zach Reardon: Yeah, absolutely. I think we, as urologists, I think you touched on or alluded to this. We're truly the gatekeepers for this patient population. I think that a majority of urologists these days probably feel comfortable handling androgen deprivation therapy on their own. If not, somebody in their group is likely doing that. So we are going to be the first ones to identify this patient cohort. I think, again, it's encouraging that these folks are usually of pretty good health and performance status, at least from their prostate cancer standpoint. And then I think that the treatment options available in this space offer a nice balance of efficacy from a cancer survival standpoint or a cancer outcome standpoint with a side effect profile. So in terms of drug tolerance and toxicity, there tends not to be a whole lot of major issues.

Obviously, there are things that we're aware of we screen patients for. Prior to starting medications, we monitor for adverse effects. Moving forward, we can adjust doses, but I don't think that it's something that's insanely intense or time-consuming that it's going to be burdensome to a urologist. I think that it's something that's unique and rewarding, I think, that as urologists we can offer these patients, I think, really good comprehensive treatment in a space where maybe medical oncologists don't have as much time to spend with these folks because they're dealing with maybe more acute or sick cancer patients.

Zach Klaassen: Yeah, that's well said. I appreciate that. It's been a great discussion. Anything we haven't hit on you want to touch on? Maybe a couple of take-home messages for the UroToday listeners?

Zach Reardon: Yeah. We were talking about this offline before we got started. I've been doing advanced prostate cancer for our practice, I think, a little over five years now. It's something that I actively sought out coming out of training, but based on the structure of our group, I ended up being the right person or the most willing person. But it's ended up being something that's been fulfilling and rewarding for me. I've enjoyed it. I don't feel like it's detracted from the remainder of my practice. I think in telling folks who are looking at getting started with this, what I'd say is whenever possible, this is a good opportunity for us to convey a message of hope to patients and families when we get together. There's been a lot of developments over the last 10 to 15 years in advanced prostate cancer therapy, so we really can offer folks tremendous results in terms of disease mitigation while still maintaining a good quality of life.

I think that it's important that not one treatment regimen or protocol is going to apply uniformly to every patient, so it is important to take time and individually evaluate patients in terms of performance status, goals of care, and other types of things. Then I think this is a good opportunity for us to develop long-term relationships with patients, as opposed to someone who may come in with an acute surgical problem that we treat and then maybe pass along to the mid-levels. These are people that you're hopefully taking care of for long periods of time, and I think part of this is establishing those personal connections that allow for sustainability, are rewarding, and really make this, I think, a special space for us as medical providers.

Zach Klaassen: No, that's a great message, particularly for those folks that are either just starting their practice or finishing residency, finishing fellowship. I think that's extremely well said. Zach, thanks so much for your time and expertise. We really enjoyed the discussion today.

Zach Reardon: Absolutely. My pleasure, Zach. Thanks.

Zach Klaassen: Thanks.