Originally published 1/2/2021
A PSMA PET/CT scan (or simply PSMA PET) like the one described below that incorporates the radioisotope Gallium-68, is the most sensitive method to detect metastatic prostate cancer (mPCa). PSMA PET has thus quickly gained wide use, including evaluating how well a patient’s mPCa is responding to therapy. It is not known, however, if such use varies from one center to another, despite international guidelines. This sets up difficulty collecting apples-to-apples data for evaluating PSMA PET/CT findings in this context. In an effort to avoid variance, the European Association of Urology (EAU) and the European Association of Nuclear Medicine (EANM) recruited a panel of international PCa experts in nuclear medicine, radiology, and urology to establish consensus statements.i Here are a few examples from their published paper of what the experts agree upon:
- PSMA PET can be used before and after any local and systemic treatment in mPCa patients.
- If treatment response is to be monitored using PSMA PET, a baseline PSMA PET should be done prior to initiating treatment.
- In evaluating response to treatment, PSMA PET should be used only if a change of disease management is expected from the results, e.g., don’t use PSMA PET if a patient’s PSA shows favorable treatment response, or if all available treatments were used and there are no more options.
- PSMA PET/CT can be used before and after any local and systemic treatment in patients with metastatic disease, including lymph node involvement.
- If androgen deprivation therapy is to be the clinical management, wait at least 3 months after initiating therapy to avoid PSMA PET detection of a misleading “flare phenomenon.”
- Patients who should be classified as responders to their treatment include those with stable disease, partial response, and complete response on PSMA PET.
- Non-responders are those with disease progression on PSMA PET.
It is the hope and intention of the panel that their guidelines will help create consistent and high-quality standards in performing and reporting PSMA PET/CT scans.
Have you heard about Gallium-68 PSMA-11? It sounds space-age, as if astronomers have assigned this name to a newly discovered star—or maybe it’s a 68-arm droid on The Mandalorian? Nice guess, but no. It’s an imaging breakthrough that’s like a galactic leap in detecting early prostate cancer metastasis.
The big picture news is a highly sensitive type of scan called PSMA (Prostate Specific Membrane Antigen) PET (Positron Emission Tomography). To understand PSMA PET, let’s look at each of the two components before we add in Gallium-68.
Prostate Specific Membrane Antigen is a kind of identification tag on the outer surface, or membrane, of prostate cells. However, when normal prostate cells mutate into prostate cancer (PCa), each cancer cell has 100-1000 times greater expression (presence) of PSMA. It’s as if PCa cells carry their own “here I am” label—if only researchers could figure out how to read it inside the body.
As the term ‘positron emission” suggests, some type of radioactivity is involved in PET scans, which are a specialized type of CT scans that rely on a class of radiopharmaceuticals called radiotracers. Radiotracers are molecules composed of radioactive isotopes (atoms that emit excess energy in the form of short-lived alpha, beta and gamma rays) bonded with a substance that PSMA will “take up” or adhere to. When such a radiotracer is administered by IV, it circulates in the patient’s body until it reaches sites in the body outside the prostate where PCa cells are clustered. These sites are called metastatic PCa. There, the PSMA on the surface of the cancer cells take up the radiotracers. As the patient moves through the scanner, bingo! The small amounts of radiation that are being emitted register distinctly on the monitor, allowing radiologists to read the cancer’s ID tags. Note: the amount of radiation from medical isotopes is so small, and fades away so quickly, that it poses no harm to the patient. However, it has revealed the presence of metastatic PCa tumors in bone, organs or other tissue.
What’s so special about Gallium-68?
Several isotopes have been in use for years to detect PCa. For example, in 2014 I wrote about the use of a commonly studied isotope, C-choline, used in PET scans to find PCa in lymph nodes. So, what’s so great about Gallium-68 (also written 68Gallium)? Clinical studies have shown that, even in men with a very low but detectable PSA after primary treatment with curative intent, Gallium-68 was “more than twice as sensitive as choline PET”[i] for detecting even small tumor migrations in the pelvic area and other sites in the body.
The reason that Gallium-68 PSMA-11 became a headliner on Dec. 1, 2020 is its status as the first FDA-approved radiopharmaceutical for PET imaging of PSMA lesions in men with PCa.[ii] The announcement was made jointly by The University of California’s two nationally ranked medical centers, UC San Francisco and UCLA, and their nuclear medicine teams.[iii] In addition to the previously demonstrated superiority of Gallium-68 over C-Choline, the UC teams conducted their own clinical trials to show that it also performs better than another isotope, Fluciclovine.
The importance of this work
If metastasis can be detected early, there are clear advantages for patients in the following cases:
- In men diagnosed with intermediate-to-high risk cancer who are considering prostatectomy, it’s important to know before such a drastic procedure if PCa has already left the gland, and where it is. This information will guide treatment decisions to optimize the best strategy to avoid recurrence.
- In men who have had primary treatment (e.g. prostatectomy, whole gland radiation, whole gland ablation) but whose PSA has begun to rise (biochemical recurrence), identifying the location of suspicious lesions maximizes planning decisions.
In addition, the Prostate Cancer Foundation (which helped fund the UC research) points out the potential use of Gallium-68 PSMA-11 in a new specialty called theranostics, in which a radioactive agent is used both for detection and the actual treatment of metastatic tumors:
Clinicians are testing whether using PSMA PET to direct radiation therapy in patients who have recurrent disease in the pelvis, or just a few metastases, will improve outcomes.
Eventually the FDA may approve PSMA targeting agents as part of a therapeutic strategy – not just to “see” the cancer, but to deliver drugs or radiation directly to sites of prostate cancer metastasis, killing tumor cells while generally sparing normal tissue.[iv]
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[i] Dorff TB, Fanti S, Farolfi A, Reiter RE et al. The Evolving Role of Prostate-Specific Membrane Antigen-Based Diagnostics and Therapeutics in Prostate Cancer. Am Soc Clin Oncol Educ Book. 2019 Jan;39:321-330.