Androgen Receptor Inhibition in CRPC
In a roundtable discussion with multiple participants, Alicia K. Morgans, MD, MPH, covers prostate-specific membrane antigen and Axumin testing in castration-resistant prostate cancer.
A 75-year-old man presented with intermittent right hip pain, but his physical exam was unremarkable and he had a an ECOG performance score of 1. Clinical work-up of the patient showed he had a PSA (prostate-specific antigen) of 32.6 ng/ mL and his trans rectal ultrasound guided biopsy Gleason score was 4+4 in the 4 grade group. He had a negative bone and abdominal/pelvic CT scan and was diagnosed with stage T2N0MO prostate cancer. External beam radiation therapy and androgen deprivation therapy (ADT) were initiated and planned for 18 months. Six months after initiation of therapy he had undetectable PSA, was asymptomatic, and his testosterone was at castrate level.
Six months after this, he complained of increasing hip pain and urinary frequency. He had a PSA level of 29.4 ng/mL and testosterone level of 10 ng/dL. Another bone scan showed evidence of 2 osteoblastic lesions in his right hip at 0.8 cm and 1.1 cm. An abdominal/pelvic CT scan showed a 2.1-cm left pelvic lymphadenopathy and he is now considered metastatic and castration resistant.
MARK KNAPP, MD: How is the PSMA significantly better than an Axumin scan or is it just slightly better?
ANEEL CHOWDHARY, MD: We have ordered a fair number of Axumin scans in Cleveland. I think many of them have been done. There are a number of times you have to do peer-to-peers on them. One of the areas where we use it is if you have more of a rapid PSA doubling time, your PSA velocity is a bit more rapid and you’re still concerned this may just be locally advanced disease and you’re trying to decide between whether it’s metastatic or you need to treat a locally advanced tumor. That’s where we use it quite a bit with our radiation oncology colleagues. That’s where we use it most that I’ve seen, trying to figure out if it’s more metastatic vs not. We’ve had quite a few of them approved, though, but on occasion, they can be denied.
ALICIA K. MORGANS, MD, MPH: If I’m going to do pelvic radiation, I just want to make sure that there’s not distant metastatic disease somewhere else before we start radiating the pelvis, because we won’t be able to affect disease that’s more distant with that radiation. But sometimes they’re denied, so I have a very similar experience. In terms of whether the PyL-PSMA is going to be better than fluciclovine, my understanding is there hasn’t been definitive head-to-head comparative trials that I am aware of. Though there are some series that do try to compare some of these different modalities like PyL-PSMA, which is one of the PSMA tracers, is more sensitive to identifying metastatic disease or for identifying metastatic disease than Axumin at a lower PSA. So even PSAs 0.2 to 0.5, and certainly in 0.5, it seems to be able to identify a reasonable percentage of patients who have positive metastatic disease. Whereas Axumin, I think, is described over 2 PSA or at least that was some of the initial reporting on its best sensitivity.
All of that being said, in this particular situation for this particular patient, I think the answer that you’re all giving is that there’s not necessarily a role for this particular type of imaging. That’s actually the right answer. Because right now, you have a patient with a rising PSA, and conventional imaging is negative. This is in the setting of castrate levels of testosterone. So, this patient meets the definition of nonmetastatic castration-resistant prostate cancer.
The reason that I wanted to make sure that we talked about this imaging is, it’s becoming more available. But the question at the end of the day is whether or not this imaging is going to change your treatment recommendation. Because we wouldn’t want to order a test without having a purpose behind that test.
CHOWDHARY: The question I have was that, a lot of times, if we’re worried that a lot of times when you have a patient who has lesions that are questionable that you’re going to biopsy or there are lesions that are questionable and you’re ordering an Axumin scan for it, would you start them on leuprorelin [Lupron] before doing the biopsy? Or do you wait until after the Axumin scan or the biopsy is done? I’m not even sure I fully know the answer but wanted to get your thoughts on that. Again, these questionable lesions, small lung lesions, you’re going to biopsy them, there could be stage IV prostate cancer. Do you wait on leuprorelin until you’ve done the scan or the biopsy? What are your thoughts on that? Because I’m always worried if it’s going to give you a false negative testing then.
MORGANS: I certainly have colleagues who have biopsied and then seen it’s not prostate cancer. More of the negatives and false positives are in lung lesions and sometimes there’s been a rib lesion or 2 that we have, just odd spaces for prostate cancer and then it turns out to not be prostate cancer. I think if the patient is asymptomatic and you can get the biopsy within a relatively short period of time, I don’t think you need to start necessarily. I think you have to think about the whole clinical context. If the patient is symptomatic, if the patient has disease elsewhere or if this looks like it’s a much more intensive metastatic disease state and the patient really needs palliation now, then you’re in a different situation if it’s 1 small questionable lesion and you really don’t know, is this prostate cancer or if this related to a new primary or some sort of inflammatory process?
In that case, I think I would probably hold back on my treatment, not because I think the biopsy is going to be negative or that the Axumin would necessarily be so effective, but because I wouldn’t want to overtreat the patient if I don’t know what’s going on in the lungs. That’s the purpose for my biopsy. I probably would even just biopsy instead of getting an Axumin. I really think an Axumin, these nuclear medicine tests, PSMA, are going to be potentially helpful for radiation to the pelvis in a biochemical-recurrent patient to ensure that we don’t have metastatic disease, or potentially for the use of stereotactic body radiation therapy. But in patients who are already on ADT, like this patient, there’s not a clear role for this type of imaging.
That’s not to say that people don’t use it. In Australia and Germany, they’re replacing all their scans with these PSMA tests, but in this case, this is another 1 of those red herrings.
We’re having a whole conversation about something just because it is coming down the pipeline and you’re going to see these in your practice. This may not be the point at which you might find it optimally useful.
EVAN LANG, MD: I’m sure that PSMA can be used or will be used very useful in the right setting. A lot of times, we have referrals from the urologists and [the patient’s] disease is very late stage. I suspect that we may not have many opportunities to use it. Probably it will be used more by urologists. We get a routine CT scan, bone scan and so I just want to point it out. We may not use that very often because, again, many times we have a referral to some at a very late stage.
MORGANS: We are all in different patterns with our referring doctors. We don’t get patients with prostate cancer until someone sends them to us, in most cases. Unless their diagnosis is wildly metastatic in the hospital, and we can see them there.