Part 1: Germline Testing and Molecular Imaging in CRPC

Alicia K. Morgans, MD, MPH (Moderator)

Associate Professor of Medicine

Feinberg School of Medicine

Northwestern University

Chicago, IL

CASE SUMMARY

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 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.

DISCUSSION QUESTIONS

• Is there a role for hereditary germline testing in this patient?
• What is the role of molecular imaging (fluciclovine/Axumin, PSMA, choline)?

ALICIA K. MORGANS, MD, MPH: There’s not a therapeutic implication at this time, but because of the patients’ high-risk features on his pathology, the guidelines now say that high-risk localized disease also should be included. However, I’m a medical oncologist, so I don’t see most of these patients. The urol­ogists are the ones who are doing the testing. I just wanted to raise the point that we should keep our eyes on [treat­ment guidelines], because it’s not for the treatment of this patient, himself, or any of those patients with local­ized disease. It is because the rate of germline mutation is expected to be over 10% potentially and may have implica­tions for family. But it doesn’t impact his treatment right now, is my understanding from the guidelines.

MOHAN NUTHAKKI, MD: The guidelines also recommend not only germline testing, but also molecular testing of the tissue in patients with high-risk nonmetastatic disease. So I don’t know. Also, in germline testing, they do the whole germline for [7 or so] genes or just the prostate panel?

MORGANS: I can tell you what I do, but the guidelines are not as clear necessarily. We do a prostate cancer–specific germline testing. We use a particular brand that we happen to have in our clinic. We use invites; you can use whatever you want, but that’s what we have been doing. They’re not always clear, to your point; they recommend additional testing as well. There’s not a treatment implication right now for this patient in terms of somatic testing, but you’re right, they do say that.

ANEEL CHOWDHARY, MD: We order the germline testing. But we are doing the NGS [next-generation sequencing] panel, as well. The reason for that is, I am a proponent of getting the NGS testing done early on. He does have locally advanced disease. At some point, just looking at the treatment paradigm [the patient is] pursuing, as he’s going to need more systemic therapy in the future. Aside from germ­line testing, you do want to know what the HRD genetic profile is, what is homologous recombination deficiency genetic—if there are any genetic mutations in that group of genes. Because even that informs us for treatment down the road, so I would do both germline testing and the NGS panel.

MORGANS: I just think it’s phenomenal that there’s such a transition, because that’s typically what we would do, too.…I just wanted to comment that, I think I was in one of these discussions a year ago and people hadn’t yet adopted all these things in their practice. So it’s exciting to see and to hear this debate and to hear this conver­sation about something that really was almost absent a year or 2 years ago from our conversation.

What are your thoughts on things like fluciclovine [Axumin] or Axumin scans or PyL-PSMA scans? Are you ordering those? Are you using those in this biochemical recurrent setting if you have negative imaging? Are you not? What are your thoughts? Because I think this is also a complex thing to integrate into our practice algorithm.

NUTHAKKI: I think they’re not available everywhere. They’re only available in 2 or 3 centers. Nobody has any experience. At MD Anderson, a couple of weeks ago, at a prostate tumor board, the president was saying that he had seen the scans from India; they were so beautiful. But he didn’t see anything at MD Anderson, even. So I don’t know where they’re available.

MORGANS: What’s interesting and important for all of us to recognize is that PyL-PSMA was just approved by the FDA.¹ So even though it’s not something we can order today, we should expect we’re going to be ordering it soon. As long as our centers and programs and nuclear medicine doctors put together the algorithm to get the marker or the tracer into our practice. Because Medicare is going to start covering it, presumably, and other insurers, as well, because it was just approved. At least, that’s my expec­tation…Does anyone have a conversation with their team about how we integrate these into practice?

TAREK SABAGH, MD: I haven’t and I’m not sure when those are avail­able, [and if those] will be done after a negative bone scan and a CT scan. Then you do that PSMA or would it come first? What are the indications?

MORGANS: I think that’s the part that’s still a little bit nebulous. I believe it is in restaging and it’s in the biochemical-recurrent state. So I think this might be an area where we could use this PyL-PSMA agent, Axumin or fluciclovine, that is approved in this setting. It’s already out there. Are you guys using Axumin scans at all?

ELAINE BEED, MD: I’m in a rural hospital; we’re in a kind of a desert but there’s big places all around. If I needed something, I could send people there, but again, these are old guys, most of the patients I see. They wouldn’t want to go [to a bigger center farther away], so we don’t have those right now. If there’s something we need, I can ask our guys and I’m sure they’d be only too happy to put them in, espe­cially if it gets paid for.

MORGANS: That’s true. That helps everybody, I think. But I’d love to hear, is anybody routinely using an Axumin scan in this biochemical-recurrent setting? I’m not saying you should, or you shouldn’t. This partic­ular patient refused radiation. Sometimes I’ve used it to make sure that the patient’s not metastatic if we’re going to do pelvic radiation to make sure there’s not more widespread disease.

ARUN KUMAR, MD: Recently I did order Axumin in 1 patient. But it was denied because that patient never received any previous therapy. Some retroperitoneal adenopathy and patient was planning to go for surgery but [they said no to non-surgical treatment]. I was trying to rule out any occult metastatic disease, but it was denied.

MORGANS: I have a feeling that’s not uncommon. Certainly, ours are denied sometimes, too. Sometimes we keep pursuing and sometimes we let them go. Anybody else with experience, either with getting it done or with a denial that they want to mention?

MARK KNAPP, MD: I had a patient recently denied on that same scan.

_Reference:

_{1. FDA approves second PSMA-targeted PET imaging drug for men with prostate cancer. News release. May 27, 2021. Accessed August 4, 2021. https://bit.ly/2TU7vhY}