Optimizing Treatment Pathways in Non-Metastatic Castration-Resistant Prostate Cancer
David Morris, MD, FACS, and Benjamin Garmezy, MD, discuss treatment options, including ARPIs like enzalutamide and darolutamide, in nmCRPC, emphasizing the importance of personalized approaches for patient quality of life and outcome improvement.
Transcript:
Benjamin Garmezy, MD: Now, in the nonmetastatic CRPC [castration-resistant prostate cancer] setting, that’s where we don’t have any image finding of disease. This is a more unique setting because once again, this is a shrinking patient population with the advent of new imaging, but we still find patients in this population. I actually had one in my clinic this week. What do we do in this? We know that the addition of these drugs can also prevent and delay the recurrence of the visualization of disease, so that development of M1 metastatic disease, and some other very helpful other quality of life metrics, such as progression of pain, progression to time off chemotherapy, etc, in some of these very valid secondary end points that we think about in clinical trials, which also are very clinically meaningful for our men with disease, who are trying to stay on the golf course or continue jogging or continue working.
Their lives look better when their disease stays local because they’re not developing…something else that’s going to prevent them from doing what they want. In this space, we have, again, the receptor inhibitors like enzalutamide and darolutamide that can be very helpful in delaying that progression. The key here is given the way the trials are, we have some ARIs [androgen receptor inhibitors] that are preferred in one space and some ARIs that are preferred in another space. More recently, this study called the EMBARK trial has suggested that there may even be a subset of men whom we can give just an AR inhibitor alone to, this trial with enzalutamide. Perhaps there, even the toxicity of androgen deprivation therapy with long-standing hormonal blockade of the entire LHRH [luteinizing hormone-releasing hormone] system. I think that’s interesting; we’re going to see how the paradigm shifts in that sense. But of course, I still think most of these patients with this disease setting will either be on intermittent ADT [androgen deprivation therapy] or continuous ADT with the addition of an ARPI [androgen receptor pathway inhibitor], some variety. Dr Morris, do you agree with that stance, and any other nuances you have from the urology opinion?
David Morris, MD, FACS: No, I think consistently we’ve seen, no matter the data set, whether it’s medical oncology claims data or urology or overall commercial claims data, we do a pretty poor job across the US of intensifying that therapy in everyone. Still about half of people are getting just ADT monotherapy, potentially with the addition of first-generation antiandrogens. That’s the low-hanging fruit, is just intensifying the metastatic hormone sensitive patients up front. You mentioned we have almost every molecule available for our use in that setting. There’s maybe a little bit of nuance between them, but that’s for the individual clinician to decide what they’re most comfortable with in terms of managing and surveillance.
I think with nonmetastatic CRPC, you pointed out the great conundrum, which is all of those trials are on run with conventional imaging with men with rapidly rising PSAs [prostate-specific antigens]. In the modern-era US, those men are getting PSMA [prostate-specific membrane antigen] scans, and if you find something small on a PSMA scan, does that mean that you would have found something on a conventional imaging or not? That’s the giant gray area where we don’t know, and so I’ll often depend on some form of conventional imaging if the molecules that I’m most interested in are more on a nonmetastatic CRPC label vs this metastatic CRPC label. If it’s a small volume of disease seen on a PET imaging but conventional imaging is negative, I would use them like I would use somebody in the trial, which means that they would be a nonmetastatic CRPC patient and have those options available because it does present some different therapy options between enzalutamide, darolutamide, apalutamide in the nonmetastatic CRPC group vs the enzalutamide and abiraterone really just for the metastatic CRPC patient.
We typically will try to backtrack almost to use old-school imaging as was done in the clinical trials, and as the new trials accumulate data on PSMA PET and if it influences outcomes and decisions, I think we’ll begin to incorporate that more. It’s not wrong to use the PSMA PET image and label somebody according to that; it’s just that we don’t have as much clinical trial data to direct us and when to switch from one therapy to the next, so we find that a bit more challenging. But I do agree with you that the big step is just going from monotherapy ADT to combination therapy, the nuance between which combination you use. You can worry about that after you’ve gotten very good at identifying disease and recognizing who needs to intensify.
I do think that consensus between you and me and our practices, a lot of those patients are probably in my clinic to start, and then I’m involving you if it’s somebody who I feel like we need to intensify on top of or they need to hear a second opinion that fits with what I’ve already presented to them.
Benjamin Garmezy, MD: Right, the key is, in the metastatic setting, when do we add in chemotherapy, right? If they’re on ADT plus an ARPI, sometimes we add in 6 cycles of chemotherapy in our various high-risk patients to hopefully delay their transition to your castration resistance.
Transcript is AI-generated and edited for readability.
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