Targeting PSMA in Prostate Cancer Treatment - Episode 7
Dr Tanya Dorff presents the case of a 72-year-old man with metastatic hormone-sensitive prostate cancer.
Alicia Morgans, MD, MPH: Let's move on to case 2. Case 2 is another patient. This time we'll have you introduce that patient. Would you mind taking it away, Tanya?
Tanya Dorff, MD: This patient is a 72-year-old gentleman who presented with an initial prostate-specific antigen [PSA] of 47.5, with potential symptoms of nocturia and low back pain. A bone scan was done due to the high PSA level, [and the scan detected] 3 bone metastases in the spine and 2 bone metastases in the pelvis. Treatment was started with androgen deprivation therapy as well as up-front docetaxel. He had a good response. His PSA dropped down to 0.3. However, 22 months later, the PSA began to rise again, and there was a progression of his disease noted, so he's now metastatic castrate-resistant and enzalutamide is initiated.
Alicia Morgans, MD, MPH: Now, Ulka, from your perspective, what do you think about the way the treatments have progressed to this point?
Ulka Vaishampayan, MD: I think the treatment done so far is perfectly appropriate. Given the PEACE1 trial data, as well as ARASENS, I think something to consider—especially in patients with high-volume disease and patients with up-front de novo metastatic disease—is to have a discussion about triplet therapy, where you do an androgen receptor inhibitor in addition to docetaxel and ADT [androgen deprivation therapy]. That is definitely a new finding in the field that can improve overall survival. I think so far the treatment plan is perfectly appropriate and it is now time to look at other treatment options.
Alicia Morgans, MD, MPH: Thank you for bringing up the triplet. I think that's really such a new aspect of our treatment paradigm, but for patients who are fit for chemotherapy—and we're proceeding with that—it seems like it's really such a low burden—as long as there's not an issue with financials and copays—to just do the simultaneous treatment with the AR [androgen receptor]-targeted agent and then that maintenance phase.
From your perspective, Tanya, particularly if you were to do a treatment that was a triplet, but even in this sort of sequenced approach that has been done for this patient, what kind of patterns of progression do you commonly see for patients who develop a metastatic CRPC [castration-resistant prostate cancer]?
Tanya Dorff, MD: I think it's very variable. Patients often ask me that question, and I sort of walk them through that. One common scenario is just a slowly rising PSA that can rise for many months or even years before there is a radiographic change or, certainly, before symptoms. In those kinds of patients, one thing to think about is sipuleucel-T. Although it was studied a long time ago—before we had all this up-front intensification—so of course this kind of a patient wouldn't have been represented, but I think there's still enough real-world evidence of ongoing utility in a patient who is asymptomatic or minimally symptomatic and has a sort of slower progression. Of course, we know that using it earlier is better than using it later. Sipuleucel-T is one thing I think about in those slow progressors. Another approach could be if there's just 1 area that's becoming more active, especially if it's symptomatic, giving radiation, and seeing how that impacts the PSA. I use that primarily in patients on 1 of the AR-targeted agents as a way of extending the duration, because you sometimes find that the resistant clones are really located in 1 or 2 areas and not the whole body and there's ongoing good disease control. Of course, in the registrational trials for those agents, we did not react to PSA alone. Treatment was only changed when there was radiographic progression. Occasionally, there is more rampant progression, and in those cases, you have to move more quickly. You have to think about a biopsy to see if there's neuroendocrine differentiation, but I think the majority is going to be a little bit more on that slow side.
Alicia Morgans, MD, MPH: I agree and I hope that it's a large majority, though. We don't always get what we wish for but thank you for walking us through that. Please continue through this patient’s case.
Tanya Dorff, MD: In this case, it was about 10 months later that the patient started to have some new shoulder pain, and the PSA was rising.
Alicia Morgans, MD, MPH: Given that, Ulka, what testing and imaging would you order at this point?
Ulka Vaishampayan, MD: This is a patient who's had docetaxel as well as an androgen receptor inhibitor. I think it is time to consider lutetium-PSMA [prostate-specific membrane antigen], and probably, given the PSA progression, I would look at doing a PSMA-PET [positron emission tomography] scan in this patient.
Alicia Morgans, MD, MPH: Jump right in, Phil.
Phillip J. Koo, MD: This is where I think it's so important to talk about what Ulka was talking about earlier about communication because I think nuclear medicine can really be a strong partner and friend as these cases come up. I think in patients who are nearly castration-resistant, oftentimes conventional imaging is your friend and it is the standard of care. But clearly, if your referring physician is thinking about PSMA and they know that lutetium-177-PSMA is something they're thinking about, you could use it as a tool to diagnose disease and see where they are. Then you'll also have it on board in case you do want to proceed with lutetium-177-PSMA. I think there are multiple benefits you can get with this test but it's really about making sure you're on board with all the team members and doing it efficiently as well.
Alicia Morgans, MD, MPH: Thank you for that because I think that we generally tend to restage using conventional imaging, but you absolutely need a PSMA PET scan if your goal is to use lutetium. If you're thinking about the options for this patient, Ulka, lutetium and beyond, what are you thinking about? What testing do you need to do? I think we heard some mention of biopsy as well. What are you thinking about?
Ulka Vaishampayan, MD: I think it is a time also to look at the genomic characteristics of the tumor so both next-generation sequencing, if possible, or even liquid biopsy testing would be critical to do at this point. In addition, you need germline testing also, because both of these could define some therapeutic options that you are not aware of at this time for the patient. It would be good to know because then you can sequence the patient accordingly and discuss each of these treatment options with the patient and make a sort of shared decision about which way to proceed first.
Transcript edited for clarity.