Testing for PSMA in Community Settings

Scott T. Tagawa, MD, MS, FACP: Bringing PSMA [prostate-specific membrane antigen] PET [positron emission tomography] into the community has some major advantages and some implications. One implication is the interpretation of imaging. Fortunately, the signal-to-noise ratio of PSMA PET lends itself to a relatively easy time of unwrapping it and learning how to interpret the images. One just needs to be aware of PSMA-expressing normal organs and the excretion of these small molecules via the urinary tract. Do not mistake ganglia, for instance, for lymph nodes.

In the setting of using PSMA PET imaging as a biomarker for advanced disease, unanswered questions are, “What is the optimal patient population for PSMA-targeted radionuclide therapy? Can we select [patients] by PSMA imaging? In the very heavily-pretreated patient population, do we absolutely need PSMA PET if there are no other treatment options and no clinical trials available?” With earlier disease settings, we can optimize a patient population for patient selection in terms of PSMA targeting. However, particularly when we are looking at combinations with AR [androgen receptor] or hormonal agents, we have to remember that PSMA PET is a moment in time, and PSMA expression may be modulated.

If PSMA expression goes up with [use of] an AR-targeted agent, and [it is] negative or low to begin with, what about when you add that in and then combine it with an agent that leads to upregulation of PSMA? That being said, the other implications for the community is to think about the timing of imaging because of the detectability rates of PSMA. Even if there is a lot of protein or mRNA [messenger RNA] per cell, there [may be] a response to an AR-targeted agent. So even though there is a higher level of PSMA [per cell], if we are scanning months later and there is a response, maybe the volume is too low to detect the PSMA.

I think that it is wonderful that we have both diagnostics and therapeutics available, or almost available, but we are going to need to really work out the differences. I think there is a lot of opportunity with PSMA PET besides the initial diagnosis or treatment-stratification implications. And can we measure response that we could not measure before on a bone scan and then replace CT [computerized tomography] bone scans and, possibly, replace radiographic progression-free survival with an earlier response end point in our phase 3 trial? That is not for today, but I am hopeful that PSMA PET is built into all of our prospective phase 3 trials, even those that are not PSMA-targeted. There is an opportunity to look at responses via PSMA PET that we have not had before.

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