Prostate-Specific Membrane Antigen and its Relevance as a Target in Prostate Cancer Imaging and Treatment


A focused discussion on prostate-specific membrane antigen (PSMA) as a target for imaging and treatment for patients with prostate cancer.


David Albala, MD:I want to take a deeper dive into the PSMA [prostate-specific membrane antigen]–targeted imaging. People who are listening to this recording probably have varying understandings of this technology. Ashley, what’s prostate-specific membrane antigen, or PSMA? How does it express? Does it depend on the prostate cancer stage or risk group? Give us a review of PSMA, what it is, why you think it’s important, and why it’s driving the future for us.

Ashley Ross, MD, PhD:PSMA stands for prostate-specific membrane antigen. It’s a protein that’s expressed in prostate cancer at about 100 to 1000 times the amount of transcript as it is in noncancerous prostate tissue or in some other tissues in the body. It’s expressed in other areas, like salivary glands, but in prostate cancer it’s overexpressed. As a transmembrane protein, it’s put onto the cell surface more frequently in prostate cancer. That gives it its specificity for prostate cancer.

When you look across prostate cancer grades, it appears to be more expressed in higher-grade prostate cancer that’s hormone sensitive than lower-grade prostate cancer. Specifically, low-grade prostate cancer—3+3=6, Gleason score 1—seems to have less expression. But it goes up with risk. It’s obvious to most of the audience that as your disease burning goes up—if you have higher PSA [prostate-specific antigen], higher amount of disease—then you’re going to see more areas of the PET [positron emission tomography] scan light up. Correlations between expression of the tissue level and the SUV [standardized uptake value], or your skin brightness, are more nuanced. The brightness risk depends on the expression of the cell, the number of cells in that area, and some of technical things that I think only Gary understands. That’s the rationale. It’s specific for prostate cancer. It’s overexpressed in prostate cancer. It’s a very good handle for these different tracers. It continues to be overexpressed in castration-resistant prostate cancer until you get a real dedifferentiated phenotype late in the game, when the cancers will sometimes lose the expression of PSMA.

David Albala, MD:Gary, maybe you could give us an idea of what types of patients PSMA is indicated for. There are 2 groups of patients who can undergo this imaging that are approved by the FDA. Could you review those for us?

Gary Ulaner, MD, PhD, FACNM:I might expand on that to go to 3 or even 4. The first 2 that you’re referring to are newly diagnosed patients with prostate cancer, who are considered in the unfavorable intermediate, high-risk, and very high-risk [categories]. For these patients, the identification of unsuspected nodal and distant metastases can change surgical planning or move you to an entirely different modality of therapy. An incredibly important application for PSMA PET is making sure you know up front where the disease is and where it isn’t and making sure patients get the best therapies in the first line.

The second group is patients who are postprostatectomy and radiation therapy, who have biochemical recurrence and whose elevated PSA has been defined. For those patients, we’ve traditionally used CT and bone scan to evaluate for the site of recurrence or, more recently, something like fluciclovine. PSMA PET has demonstrated the strongest sensitivity for identifying sites of recurrence and allowing us to design the most directed therapies to maximize effectiveness and minimize adverse effects from therapies. Those are the 2 that you wanted me to comment on.

Let me throw in at least 1 more: any patient being considered for PSMA-targeted therapy needs to undergo PSMA-targeted imaging. Therapy targets that PSMA molecule. If PSMA-targeted imaging doesn’t demonstrate avid disease, then the therapy isn’t going to be effective. This is a way of classifying patients according to their likelihood of responding to PSMA-targeted therapy. I consider it essential before any PSMA-targeted therapy and PSMA-targeted imaging study is performed.

There’s possibly 1 additional category, as defined by the Society of Nuclear Medicine and Molecular Imaging Appropriate Use Criteria: patients with castration-resistant prostate cancer who are thought to be M0. In these patients, PSMA imaging may classify them as M1. This can greatly change how patients are managed. I would choose 4 groups of patients—initial diagnosis, high-risk, biochemical recurrence, prior to any PSMA-targeted therapy—and then consider M0 castration-resistant prostate cancer.

Transcript edited for clarity.

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