A roundtable discussion, moderated by Michael Morris, MD, discussed the current landscape of radioligand therapy in prostate cancer, including recent trial highlights presented at ESMO 2023. Dr. Morris was joined by Tanya Dorff, MD; Evan Yu, MD; and Rana McKay, MD.
In the next segment of the roundtable series, the panel discusses recommended frequency of scans for patients receiving radioligand therapy, PSA response, and whether to give a full 6 doses of this treatment.
Dr. Morris: I think that there is a whole lot of ambiguity in terms of following these patients. We’ve talked a lot about how to select patients now, but we don’t really know should we be getting or can we even get serial PSMA PETs as some investigators in other countries have the benefit of doing? Whether we should be getting standard scans on these patients? When should treatment be terminated if it looks like they’re not responding. Why don’t we start with Evan. How do you manage that at your center?
Dr. Yu: Yeah, it’s a really good question, and the truth of the matter is what we do, I’m not 100% sure it’s the right thing to do, but we are doing serial imaging with PSMA PET, and about once every 6 weeks, and we’re learning a lot from that. However, I think we need to take some caution is that PSMA PET treatment response has not been established as the end-all, be-all yet. Traditionally, we’ve used progression on CT and bone scans as per the Prostate Cancer Working Group criteria, at least in clinical trials, and I personally have some reservations about seeing maybe some SUV [standardized uptake values] increase or a new lesion by PSMA PET and saying, “This isn’t working, let’s take you off.”
I think it may also depend upon the therapy you’re using. In this instance, we’re talking about lutetium 617 PSMA, but there are people that are applying serial PSMA PET imaging scans to abiraterone, enzalutamide, docetaxel, and we have clinical trials that we’re doing that and we’re hoping to learn more from that. I would say that in our early experience, it doesn’t always correlate perfectly with what’s happening with PSA [prostate specific antigen], and what’s happening on CT and bone scans. I guess I would urge some caution at this point in time, even though we’re doing it, we’re learning and we’re eventually going to publish results, but I think we don’t exactly know whether that’s the right thing to do, to do PSMA PET treatment response following.
Dr. Morris: No question. We’re all learning and trying to figure out that ideal algorithm and build up the data to know what follow-up is looking like. But Tanya, is there a kind of a patient that you would say that you can clearly identify as progressing, and you would stop treatment after a certain amount of, let’s say, symptomatic PSA-based or imaging-based data would suggest progression. How long do you give that until? Is that after 1 dose, 2 doses, 3 doses? Is there any advice that you would have in terms of when it’s time to move on to another therapy as opposed to just push through and give all 6 doses?
Dr. Dorff: As oncologists, I think we’re used to dealing with sometimes conflicting data from a patient and have to make these complex decisions about is the treatment working and how long do I keep going? I would not typically stop after just 1 dose unless the patient is clearly just deteriorating so much clinically that whether it’s disease or toxicity, it’s just not going to happen. With chemotherapy, we know PSA can go up before it goes down. With this treatment, I’ve found some of my patients, PSA does go up before it goes down, so I would try not to stop just for PSA changes, but really I look at the patient, if the patient’s pain goes away after the first dose and their PSA is up, we’re treating the patient and not the numbers.
If there are discordances between what’s happening with the PSA, what’s happening with the patient, and I’m not certain, that’s definitely where I use imaging, so I try to add that as an adjudication, so to speak. If it’s clear, if PSA is going down and the patient is getting better, then I’ll delay the repeat imaging and just try to work off those clinical parameters.
But I think it becomes pretty clear, just as we’ve learned with chemotherapy, when a patient is just not benefiting. They’re having more pain, their numbers aren’t looking good, they’re getting weaker and worse, and then it’s time to move on. Sometimes it’s more challenging.
Dr. Morris: Generally, how many doses do you try and make that adjudication on? Like you said, I won’t make that decision on 1 dose, but will you do it at 2, will you do it at 3, or you take it case by case? How do you handle that?
Dr. Dorff: If it’s a slam dunk that the patient is benefiting, as I said, I’ll delay the imaging until after the third or fourth cycle and then really decide how many more to give at that point. But I try to give at least 2, and then if it’s not clear based on the labs and how the patient’s looking, that’s where I would do the scan and use that to help make that decision.
Dr. Morris: Let’s flip the situation on the other side of that coin. Rana, let’s say I have a patient who is doing really well after, let’s say, 2 doses. PSA is now no measurable amount. Let’s say you order a PSMA scan, you don’t see any disease. Are you going to go ahead and push through and give the subsequent doses, or are you going to hold off? What’s your approach to this? There’s no right or wrong answer here. We don’t know, but I think that perhaps the audience will be encountering these issues and would appreciate your own pearls of wisdom on this.
Dr. McKay: Yeah, absolutely. I think we just have to be really cautious with this therapy. For those patients that are experiencing a dramatic PSA decline with dramatic symptom improvement and they’re reaching that PSA 50 pretty early on, I don’t think it’s unreasonable to hold, monitor them for a period of time, let their marrow recover, and not necessarily just continue to blast away with all the remaining 4 cycles. There is a precedent for doing that now with some data that we’ve seen recently presented about adaptive-based dosing of lutetium. I think that it logically makes sense, but I think you also need to, in talking with the patient initially as they’re starting therapy, setting expectations, because I think if patients have the expectation that they are going to absolutely be receiving the therapy every 6 weeks and then some things shift, they’re like, “Why did that shift?”
I think having that conversation upfront to say, we’re going to start you on this therapy. We’re going to monitor your clinical symptoms, your laboratory values, PSA, blood counts, alkaline phosphate, and your imaging, and based off of those 3 parameters, we’re going to decide whether you get more or less therapy or we stop. I think going in with that notion than the patient is aware that, “Okay, we’re going to see how it goes, and based on these things we’re going to adjust.” I think that is something that could potentially be applied.
Dr. Morris: I think this is something that medical oncologists in particular have to do some education on, because when we give chemotherapy with diminishing tumor burden, the dose of exposure of any individual cancer cell is the same. If you give a dose of docetaxel, whether you have a lot of disease or a little disease, you have the same AUC [area under the curve], and the cancer is receiving the same amount of chemotherapy. But with radioligand therapy, the less disease that you have, the less of a dose your tumor is going to receive, because you need to target, and it’s all about the dose of radiation. We have to begin to think about new treatment paradigms, and keeping your powder dry, perhaps, and saving your subsequent doses for a later period. This is completely investigational, and we’re now beginning to see some trials with adaptive dosing schedules. We’re going to talk about 1 of those a little later in this discussion, but I think as a field, we need to appreciate this is not chemotherapy.
Now, what some centers do in order to estimate whether the patient is still receiving a good dose is do a dosimetry scan after injection. We do that, so we’ll inject and then run the patient through a scanner and see what the amount of drug that the tumor is now absorbing. Is that something that your centers do as well, Tanya?
Dr. Dorff: Yeah, our nuclear medicine physicians, not in every case, but I feel like in certain cases they want that SPECT scan. I think that’s what you’re talking about to see where the dose of drug is going.
Dr. Morris: Yup. Evan, how about in your center?
Dr. Yu: Yes, the answer is yes. Absolutely.
Dr. Morris: Rana, yours too?
Dr. McKay: Same as well, unless there’s a patient factor where they don’t want to come in the next day and do the additional scan.
Dr. Morris: I recognize that all 4 of us come from institutions in which that is feasible, and it’s certainly not necessarily common practice, and in the community might not be an available option. But it’s another data point in making a decision as to whether to keep going or to abandon treatment. Even on the progression side, like the patient that you were talking about, Tanya, if you do that scan and you see actually the patient’s progressing and the tumor is not taking up drug, that’s certainly a reason to move on to something else.
Indeed, we will see patients progress with PSMA avid disease and patients progress without PSMA avid disease, and you need to make that distinction in terms of thinking about whether to press on or what treatment to get next.