Real-world experience and clinical trials have shown the utility of prostate-specific membrane antigen positron emission tomography (PSMA PET) in prostate cancer, from “newly diagnosed unfavorable intermediate-, high-, and very high-risk prostate cancer” to “biochemically recurrent disease” to “metastatic disease.” Neeraj Agarwal, MD, FASCO, provides insights into the current role of PSMA PET scans in the treatment of various stages of prostate cancer and the potential future role of this imaging technology in the prognostication of disease.

In prostate cancer, there are currently 3 situations in which we should be doing PSMA PET scans. The first is patients with newly diagnosed unfavorable intermediate-, high-, and very high-risk prostate cancer with a computed tomography (CT) or bone scan that does not show metastasis. These individuals may be getting ready for surgery, but their PSMA PET scans may show 2 or 3 lesions in distant bones. For these patients, instead of surgery, I may offer radiation therapy to the primary site and to these oligometastatic sites. So, in this setting, PSMA PET may redirect the plan from local surgery to systemic therapy with selected prostate- and metastasis-directed radiation therapy.

The second scenario involves patients who have received surgery/radiation therapy and are now experiencing biochemical recurrence. I want to order a PSMA PET scan in these cases to see if the prostate-specific antigen recurrence is happening because of regionally localized metastatic disease or distant metastatic disease. The presence of distant metastases on the PSMA PET scan may reduce the likelihood that salvage radiation alone will be appropriate, and I see a clear role of PSMA PET scans here in determining whether patients should get a combination of salvage and/or metastasis-directed therapy and/or systemic therapy.

In the third scenario, PSMA PET scans have a clear role in the metastatic castration-resistant prostate cancer (mCRPC) setting when there is a potential role for ¹⁷⁷Lu-PSMA-617 treatment. In this situation, it is pretty straightforward: all patients being considered for PSMA-targeted radioligand therapy should undergo PSMA PET to confirm eligibility.

So, there is currently a clear role for PSMA PET scans in 3 different stages of prostate cancer: (1) newly diagnosed unfavorable intermediate-, high-, and very high-risk prostate cancer with no evidence of metastasis on the conventional CT or bone scan; (2) biochemically recurrent prostate cancer; and (3) mCRPC. And this may continue to evolve as we continue to collect additional data in the hormone-sensitive prostate cancer setting.

Regarding the use of PSMA PET for prognostication, current evidence is insufficient to use standardized uptake value measurements alone for routine clinical decisions. Higher PSMA uptake may indicate greater PSMA expression and a higher likelihood of response to PSMA-targeted radioligand therapy, but it does not necessarily indicate more aggressive or widespread disease. Low or heterogeneous uptake may reflect reduced PSMA expression and, in the appropriate clinical context, may raise concern for tumor dedifferentiation or neuroendocrine transformation. However, validated guidelines for incorporating standardized uptake value and other quantitative PSMA PET measures into individual patient prognostication are not yet available.