A prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan is a new type of nuclear medicine procedure for men with prostate cancer. PSMA PET scans are currently most commonly used in two different clinical scenarios; (1) in men with newly diagnosed prostate cancer who are at risk for metastatic disease, and (2) men who have previously been treated for their prostate cancer with curative intent (e.g. with surgery and/or radiation) and now have suspected persistent or recurrent disease based on a rising prostate specific antigen (PSA) level in their blood.
In 2020 and 2021, the United States Food and Drug Administration approved two different PSMA PET agents, 68Ga-PSMA-11 (now commercially available as TLX591-CDx, trade name Illuccix®) and 18F-DCFPyL (commercially available as piflufolastat F 18, trade name Pylarify®). These agents are very similar chemically and both offer highly sensitive detection of sites of prostate cancer. Both agents are approved for the same two clinical scenarios as outlined above. Although there may be subtle differences between the two agents, there have not been any clinical trials demonstrating any substantive difference between them when they are used clinically according to the prescribing information in the package inserts.
For both 68Ga-PSMA-11 and 18F-DCFPyL, multi-center prospective trials have demonstrated the utility of those PET radiotracers for finding small sites of disease that cannot be detected with other imaging modalities and can have a significant impact on the selection of treatment options for men with prostate cancer.
For men with newly diagnosed prostate cancer, PSMA PET has a moderate sensitivity but very high specificity for identifying lymph nodes in the pelvis that harbor prostate cancer; this means that an abnormal lymph node on the scan is almost certainly prostate cancer and the urologist or radiation oncologist can adjust their planned therapy accordingly. This also means that a substantial number of men will have scans that do not show abnormal lymph nodes, even though prostate cancer is present in the nodes. For such men, there may still be important prognostic information in the scan. Further, in a small number of men with newly diagnosed disease, unsuspected distant metastases (i.e. foci of disease outside of the pelvis) will be found on the PSMA PET scan. This is uncommon, but will often have a profound affect on the chosen therapy.
For men with persistent or recurrent disease, PSMA PET appears to be the most sensitive modality available for identifying sites of disease. In men with very low PSA values, slow PSA rises, and lower grade-group/Gleason scores at initial diagnosis, there may be reduced detection efficiency of the scan. Nonetheless, both positive scans and negative scans can impact decision-making and therapeutic options for men with persistent or recurrent disease.
Ultimately, despite the promise of PSMA, there may be scenarios in which it is less effective at finding sites of disease than other modalities. For some men, other types of PET scans (18F-fluciclovine or Axumin®, or 11C-choline) or traditional bone scintigraphy, computed tomography, and/or magnetic resonance imaging may be the imaging methods of choice.
Figure 1. 68Ga-PSMA-11 PET images of three different patients, demonstrating pelvic bone metastases (left), pelvic and retroperitoneal lymph node metastases (middle), and diffuse bony metastases (right).
For more information see the following:
Appropriate Use Criteria: Prostate-Specific Membrane Antigen (PSMA) PET Imaging
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Video: Primary Author Dr. Hossein Jadvar discusses AUC development process
Information from pioneers in the field, Dr. Baum and his team in Bad Berka, Germany.
A look at the use of PSMA agents in prostate cancer management:
A discussion between a radiologist, a medical oncologist, and a urologist on how PSMA scans influence patient management: