Targeting PSMA in Prostate Cancer Treatment - Episode 3

Case 1: Metastatic Castrate-Resistant Prostate Cancer

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Dr Ulka Vaishampayan presents the case of a 67-year-old man with metastatic castration-resistant prostate cancer.

Alicia Morgans, MD, MPH: Why don’t you present for us the first case, if you would?

Ulka Vaishampayan, MD: This is a case of a 67-year-old man who presented first to his primary care physician with reduced urinary flow. He had some hematuria and pain in the left hip. His past medical history is significant for hypertension and well-controlled blood pressure with medication. His work-up shows a PSA [prostate-specific antigen] level of 7.4 ng/mL. Prostate biopsy shows a Gleason aid 4+4 prostate adenocarcinoma. A bone scan was done, and that showed a lesion in the left pelvis, as well as the left lower lobe of the lung. His performance status is 0. He’s otherwise fairly healthy and the treatment was started with androgen deprivation therapy as well as abiraterone. The patient responds to treatment, and his PSA goes down to about 0.2 ng/mL.

Alicia Morgans, MD, MPH: Thank you. Phil, As a nuclear medicine physician, what are your thoughts on whether a PSMA [prostate-specific membrane antigen] PET [positron emission tomography] scan would be useful in this setting, where we have conventional imaging demonstrating radiographic evidence of metastatic disease?

Phillip J. Koo, MD: That’s a great question. It’s interesting because when we had these PET agents like choline or fluciclovine approved years ago, they were approved only for patients with biochemical recurrence. Then PSMA-11, when we had the Gallium 68, it was a groundbreaking day also, because there was also an approval for use in patients before definitive therapy. Then the NCCN [National Comprehensive Cancer Network] Guidelines also recommend this in patients who are unfavorable with intermediate-risk, high-risk, and very high-risk disease. Then you wonder about this type of patient. Could they have gotten a PSMA? Would it have been beneficial to get a PSMA PET agent in this patient? That’s 1 question. In this specific case, in a patient who already had conventional imaging with metastatic disease, what would the value of a PSMA PET scan be? I don’t think we know the answer. The only advice that I always give to referring physicians is to make sure before we get the test. We think through the possibilities, and we make sure the test is actionable.

Alicia Morgans, MD, MPH: I agree with that completely. Is this going to change our management? Why does it change our management? That’s an important series of questions to ask. Tanya, what do you think about the management of this patient? Would a PSMA PET scan have changed your decision-making for this patient?

Tanya Dorff, MD: If the metastases had been identified only on PSMA-PET, it would be a lot more of a gray area. We might be tempted to do metastasis-directed therapy, but there aren’t the kinds of robust prospective trials incorporating that with systemic therapy to know that we’re impacting outcomes. There are ongoing trials, like SWOG S1802, that are going to allow us to look at this question. But because it was seen on conventional imaging, that’s how we have for decades categorized patients as metastatic. Let’s say we saw 3 more areas of disease. I don’t know that the additional PSMA PET would have impacted management, but he’s getting appropriately some intensified systemic therapy.

There are a couple of questions about going another step or 2 further. For instance, the STAMPEDE trial showed that radiation in the prostate primary in the setting of low-volume disease was beneficial. The PEACE1 trial showed that adding radiation didn’t interact with the other systemic treatments and that abiraterone was still beneficial after using up-front docetaxel. We’re being asked to think about triplet therapy. Do we give this gentleman docetaxel as well as abiraterone? How does that interact with radiation in the prostate primary? There are more questions than answers in some ways, but it’s a lot to discuss with the patient. Not every patient is going to be a candidate for triplet therapy, but it has to at least be in our minds as we walk through a checklist of how to decide on the initial approach.

Alicia Morgans, MD, MPH: I agree. This was a patient with de novo metastatic disease, which was an entry criterion for the PEACE1 trial. We do look forward to seeing the ENZAMET data by volume to have some understanding of a broader population receiving the triplet therapy as well. Let’s go back to Ulka so she can tell us more about what happened with this patient after initial therapy.

Ulka Vaishampayan, MD: The patient had a PSA remission of nadir of 0.2 ng/mL. Now 13 months later, the same patient presents with a rising PSA up to 5.7 ng/mL. His PET CT shows enhancing lesions in the lung and ribs. At this point, the patient was initiated on docetaxel treatment, which was given for 6 cycles and was well tolerated. His PSA responded, and his nadir was 0.1 ng/mL. Fifteen months later, his PSA is beginning to rise and is 1.4 ng/mL at this point.

Alicia Morgans, MD, MPH: Dr Dorff, what would you do next? We have PSA progression with this patient, who has already had treatment with abiraterone and docetaxel.

Tanya Dorff, MD: He hasn’t technically met PSA progression criteria by the Prostate Cancer [Clinical Trials] Working Group, but I’m going to get imaging because we want to know how if this patient is progressing. Sometimes if there is oligoprogression, with just 1 active site of disease, there are some published experiences giving focal radiation. But I always look at the PSA, the patient and their symptoms, and the imaging before deciding what the next treatment might be. If this patient hasn’t had genomic testing and germline testing, that should be done at this point, particularly if it can be done from tissue. If it’s going to be a liquid genomic test, we might wait for a little more disease activity to get a better sample.

Transcript edited for clarity.