The Role of Androgen Receptor Inhibitors in the Management of Advanced Prostate Cancer - Episode 7

PSA kinetics in advanced prostate cancer


In response to a presentation from AUA 2021, Dr. Julie N. Graff considers the role of PSA kinetics as prognostic markers in advanced prostate cancer.

Benjamin H. Lowentritt, MD, FACS: We’re getting a lot of information on the practical real-world experience from use of these agents. There were a couple of abstracts recently presented at the AUA [American Urological Association] 2021 Annual Meeting that recently happened virtually from Las Vegas [Nevada]. One of these was looking at PSA [prostate-specific antigen] kinetic data on the combined TITAN and SPARTAN studies. This was an apalutamide study.

I always think this is an understated necessity of how we look at these drugs. We’ve gotten so used to saying that PSA response isn’t everything and that survival is really important. But when you think about these patients, especially the patients with nmCRPC [nonmetastatic castration-resistant prostate cancer], their entire disease has lived in PSA. Maybe they were treated and then had their PSA rise. They never were proven metastatic. They were put on all these therapies. They failed those and are now going on a new therapy because their PSA is rising again. If we don’t show a profound PSA response, then patient compliance, adherence, and psychology are going to be big issues. We’ll have people coming off the drug earlier than the trial suggested because [they feel] they aren’t getting the response in their entire disease.

This is getting a little off-track as far as why for the patient. Do you have any thoughts on that, Julie? To me, PSA data are still critical, although we don’t want to overemphasize that.

Julie N. Graff, MD: I’m glad you’re bringing this up because, as you know, we have treatments that don’t decrease the PSA, like sipuleucel-T and radium-223. It’s funny because patients are wedded to their PSA. Then they go on other treatments, and you say, “Forget about it. Don’t worry about the PSA. That’s not the focus anymore.” And they’re like, “What?”

I hear you. First, this idea of PSA depth isn’t new. If you look at SWOG-9346, Dr Maha Hussain wrote a paper looking at the depth of PSA on castration alone and how that resulted in different survival times, where if you got it under 0.2 ng/mL, you did the best. That concept is coming back with apalutamide. It’s not mysterious that if you’re able to wipe out more of your disease, you’re going to live longer.

But when you’re sitting across from a patient whose PSA goes from 30 to 20, then to 18, but then 19 ng/mL, it’s not going to keep going down. It would be foolish to abandon it. I hear your statement that the patient might feel discouraged. Yes, he might. But as providers, we need to say, “We still think this is benefiting you on some level.” You might even look before starting the drug, and maybe the PSA was increasing very steeply and now it’s leveled off. Those are opportunities for clinical trials to ask what we can add to this to get more disease eradication.

In our clinical decision-making, we still think about the PSA, imaging, and how the patient is feeling when we change therapies. I’ve certainly seen some patients who were on enzalutamide for a month, abiraterone for a month, and chemotherapy for 3 cycles. It’s not a race to get through all these treatments. You have to milk them for everything they’re worth. I’d look at these kinetic data and say this is a great opportunity to do research. For these guys whose PSAs don’t get down to under 0.2 ng/mL, what do we need in addition to these AR [androgen receptor] antagonists to help that happen?

Transcript edited for clarity.