Balancing Aggressive Treatment and Quality of Life in Prostate Cancer Therapy

In the second part of this roundtable, Drs. Jacob Ark, John Finnie, Gautum Agarwal, Seth Strope, and David Bryan discuss the critical factors for identifying and managing progression in prostate cancer. The conversation covers both localized, low-volume disease and metastatic and castration-resistant stages. Key topics include the importance of risk stratification tools like PSA velocity and doubling time, the evolving role of precision medicine with ctDNA and germline testing, and balancing aggressive treatment with patient quality of life.

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Dr. Ark: To that, when you’re talking about risk factors for going on to not just castration-resistant, but metastatic disease, we’re talking localized space, low-volume, castration-sensitive, what are some of the factors that you’re looking for, testing for? And how is it changing maybe some of your treatment plans to help delay going on to disease progression of the two examples being you’re localized, how do you identify and prevent going to metastatic castrate-sensitive, you’re metastatic castrate-sensitive, how do you identify and help prevent moving on to castrate-resistant? And this is to anybody who is wanting to field the question.

Dr. Agarwal: Well-

Dr. Finnie: I think I’d like-

Dr. Agarwal: Yeah, you go ahead.

Dr. Finnie: I could say a few things, just what I’m thinking about. So, basically, it’s so important how old are they. Is this some 85-year-old guy, he’s going to be maybe doing active surveillance? Do you want to use a decipher score, or something like that? They can be so helpful to risk stratify somebody. Are they younger? Are they older? If somebody is localized and they look unfavorable to high-risk, they’re young, then you’re going to want to do more aggressive therapies, contrast that with somebody who is maybe 82 doing a lot more active surveillance. We know the older they get, these octogenarians were not really thinking radiation becomes more of a modality that we’re using in those types of patients.

So, for the localized patient in that setting, I do find it interesting. I still very briefly mention what is almost unheard of now, these days, I’ll just briefly mention about 20 seconds, say orchiectomy is the least expensive option. We don’t really recommend that at all, but I briefly mentioned it. If somebody said, “Is there something you can do? I never have to see you again,” I put that out there and I say, “It’s an NCCN guideline,” but I quickly say, “We’re not going to do that,” but help them understand the role of how testosterone, the whole mechanism, the pathway. And it also gets into all the things we’re going to talk about, the different orals, what’s out there now, they’re so potent, the various antigen receptor inhibitors versus the things hitting the adrenal biosynthesis pathway.

Dr. Ark: Right.

Dr. Bryan: That had to be the worst randomization trial ever, right? Orchiectomy versus ADT.

Dr. Finnie: Oh. Really low-yield in one arm. One arm just didn’t seem to accrue.

Dr. Ark: Hard to blind that one.

Dr. Agarwal: Exactly, exactly.

Dr. Strope: But I think that goes to the point though, too. A lot of times, patients already have an idea of what they want. There’s a lot of patients who go in and go, “I don’t want to be aggressive. This isn’t my concern,” almost to the point it’s like, “Well, then why were you checking your PSA?” So it’s interesting where patients fall on their own spectrum of what they want to do.

Dr. Ark: Yeah.

Dr. Agarwal: I agree with that 100%. Me and John talk about this all the time at conference. And I think that, yes, could you give somebody a combination of every possible drug that’s available upfront? And then you look at that science and then there’s scientists who come up with that, “This works.” But then when we’re facing the patient, you’re like… You have a person who’s vital at 55, vital, living his best life. And then you’re like, “I get it.” Upfront, you’re trading off your most vital years, 55 to 65. You’re trading that so you can be alive at 75 when life sucks.

Dr. Ark: Right.

Dr. Agarwal: I’m sure life is still okay at 75, but you know what I’m saying? It’s like a trade-off. And so it’s a constant battle between what is your goal as a patient, what do you want out of life, how much treatment do you want, because stuff still works at lesser severities.

And then the other point of it, I think, that’s really key is how do we determine what is actually happening in that patient’s cancer, because there’s two theories, right? You could say that, the minute the prostate cancer is found locally, they’ve already metastasized, right? There’s that theory of metastasis occurs at the origin of the actual cancer. And so you could do local treatment, but they’re going to have a recurrence. So, having markers besides PSA, like circulating tumor DNA, that says, at the time of their prostatectomy, before you do the surgery, their ctDNA was negative. So, you could have a chance for cure with just that treatment, or if they’re positive, maybe you have to be more aggressive with systemic therapy upfront. We’re seeing that with bladder cancer. And obviously, sometimes in kidney now, the data is coming. So that’ll be interesting how that plays out. But for me, PSA velocity, doubling time, density, all those things add to the armor of easy tests to figure out how much you should do.