Role of PSMA PET Imaging in mCRPC

EP: 1.Polling Questions: Advanced Prostate Cancer

EP: 2.Patient Case #1: Treatment Selection in mCNPC

EP: 3.Role of Conventional Imaging vs PSMA PET in mCNPC

EP: 4.Treatment Options for High-Volume mCNPC

EP: 5.Patient Case #2: Choosing Optimal Therapy in mCRPC

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EP: 6.Role of PSMA PET Imaging in mCRPC

EP: 7.Sequencing Therapy for mCRPC

EP: 8.Optimization of Genetic Testing for mCRPC

EP: 9.Recap: Recent Advances in the Treatment of Metastatic Prostate Cancer

Raoul S. Concepcion, MD, FACS: Lenny, a little bit different question for you. We had alluded to PET [positron emission tomography] molecular imaging, PET/CT scanning. We believe that the indication for PSMA [prostate-specific membrane antigen] is anyone for whom we’re worried about metastatic disease. Obviously, Axumin, or fluciclovine F18, scanning has been available, and that indication was for patients who have failed therapy. What are your thoughts, particularly in this patient because he’s obviously failed therapy? Comment if you will, on pluses and minuses of Axumin versus PSMA.

Leonard G. Gomella, MD, FACS: We have become virtually an exclusive PSMA shop. We’ve got it here at Thomas Jefferson University since early April. I will say it’s shocking me how it is changing our treatment of patients. I’ll give you one example. A person had a radical prostatectomy by me about 25 years ago, has had slowly rising PSA [prostate-specific antigen], going up and up, got up to about 2, 2.5 ng/mL. We put him on intermittent hormone therapy, then continuous hormone therapy. Then he started to manifest metastatic castration-resistant disease [mCRPC]. PSA went to 1.5 ng/mL. Standard imaging is negative. And PSMA shows he’s riddled with metastases. He’s absolutely riddled, completely asymptomatic. Oliver mentioned this, and I think my medical oncology colleagues, in ASCO [American Society of Clinical Oncology] there’s been a white paper that has come out saying be very careful how you use PSMA today, particularly in the context of a clinical trial. But it’s completely changing what we do.

Our only problem with PSMA however is, if it’s a straight Medicare patient here in Philadelphia, we have no problem. The minute we get involved in a supplement or anybody under the age of 65, the amount of time that we have to spend begging and peer-to-peer reviews and things like that make it very difficult. But there’s no question to your point that I think PSMA is basically going to knock Axumin and all of the others out of the water until we get the next generation of PSMA that comes down the line. It’s going to be revolutionary in how we understand prostate cancer.

Raoul S. Concepcion, MD, FACS: Are you getting it Lenny, are you routinely using it for staging, especially in high grade, high risk?

Leonard G. Gomella, MD, FACS: Yes. Any man who has a high risk. Again, our problem is that patient population that we’re considering for radical prostatectomy. High-volume disease like this gentleman was, under the age of 65, it’s very difficult for us to get it. And every once in a while, I’ll have a patient who wants to pay the $6500 out of pocket. They really feel that they want to have it. But yes, we’re using it for staging. We have a clinical trial that’s associated with some of the VISION study work where you have the PSMA and then a radical prostatectomy. We are big believers in a very short period of time of the power of PSMA redefining prostate cancer.

Raoul S. Concepcion, MD, FACS: Jason, do you have any issues in the Detroit area? Is PSMA available to you?

Jason M. Hafron, MD, CMO: It’s not widely available. We have similar experience as Leonard, but our hospitals are just getting it online. But I think Leonard said it best. It’s going to redefine prostate cancer. We’re going to be in places that we never imagined. It’s disruptive technology. I don’t see the future role for Axumin. As we get PSMA online, Medicare’s going to cover it in 2022. That’s going to be our go-to test for staging and for recurrence.

Raoul S. Concepcion, MD, FACS: For the viewers, it’s important to understand that there are different agents and different labels. There’s obviously Pylarify [piflufolastat]. Then you have Gallium PSMA, which is limited to UCLA [University of California, Los Angeles] and UCSF [University of California, San Francisco]. There are going to be a couple of other agents coming to the market. Some of these are renally cleared; some of these are hepatically cleared. There’s going to be a whole menu of PSMAs, and I would encourage the viewing audience to bone up on this if you will because as Lenny said, this is going to change the face, especially for the patients we consider high grade, high risk localized. These patients are going to be restratified.

In the last 10 minutes, because I want to give some time for comments; in the polling question, if the patient in case 2 had received prior docetaxel and progressed, what would your treatment of choice be? Would you switch over to an antigen receptor targeting agent, whether it’s ABI [abiraterone], enza [enzalutamide], or obviously because cabazitaxel is approved in patients who have failed or have not tolerated docetaxel, would you go to cabazitaxel, or other?

Raoul S. Concepcion, MD, FACS: Dan, if you had a patient who had received docetaxel and then progressed, where do you tend to go for your next line of therapy?

Daniel P. Petrylak, MD: If they’ve received docetaxel then progressed in hormone sensitive, I’ll go with a next-generation antiandrogen therapy as the first treatment. Then I will consider going on to cabazitaxel afterward. A lot of it will also depend upon the rapidity of the disease progression, what their molecular profiling is. Clearly, if it’s appropriate for them to receive a PARP inhibitor at some point, I would do so. The other thing we always have to look out for is microsatellite instability [MSI]. I’ve seen some very dramatic responses to pembrolizumab in patients with microsatellite instability. In fact, I’ve got a CR [complete response] right now in a patient who had been on both doce [docetaxel] and cabazitaxel. That’s another molecular marker we’ve got to be sensitive to.

Raoul S. Concepcion, MD, FACS: Oliver?

Oliver Sartor, MD: Dan nailed it. We must remember these rare groups of patients who have either MSI-high, mismatch repair, or high tumor mutational burden [TMB]. Some of these PD-1 inhibitors, and pembrolizumab in particular; I mention it by name because it’s FDA approved in that setting, high MSI, TMB, or mismatch repair deficient. Some of the responses will knock your socks off. I’ve got one guy who is in complete remission, off hormonal therapy, still in complete remission. And he’d already failed abiraterone and docetaxel. You can’t miss it because it can make a huge difference in the lives of patients. The genetic testing is not going to benefit the majority of patients, but for the rare patients, it can make a huge difference in their lives.

Raoul S. Concepcion, MD, FACS: You and Dan both bring up a great point, that for a while there we just fixated on individual biomolecular markers, looking at precision medicine and trying to determine the next line of therapy. And again, what you’re both saying is that as these patients progress through first, second, third lines of therapies, we must be cognizant of what molecular testing can be done, whether it’s homologous recombination, mismatch repair, like you said Oliver, MSI, CDK12, because these are actionable mutations. And again, we have multiple drugs. We have drugs in different categories, whether it’s PARP inhibitors, whether it’s immunotherapies, checkpoint inhibitors, and there are going to probably be more and more over the next few years.

Transcript Edited for Clarity