Originally published 5/2/2019
PSMA-PET scans have become the most sensitive prostate cancer (PCa) detection for metastasis (cancer that has spread to other parts of the body), including recurrent PCa after treatment. PET uses a radioactive tracer that has been molecularly bonded with a substance readily taken up by prostate specific membrane antigen (PSMA). PSMA is abundant on the surface of PCa cells. When scanned under CT, the tracer “lights up”, revealing even very small sites of PCa spread. PSMA-PET imaging now replaces conventional CT and bone scans formerly used to check for metastasis before planning PCa treatment. Since the post below, the FDA has approved two injectable radiotracer drugs for PCa diagnosis. Approval of the first drug, Gallium 68 PSMA-11 (Ga 68 PSMA-11), was announced on Dec. 1, 2020. Then, on May 27, 2021, news came that the second drug, piflufolastat F 18 (brand name Pylarify), had also been FDA-approved. Seven months later in December 2021, the FDA announced approval of a kit for producing Gallium 68 PSMA-11. The kit, named Illuccix, is expected make Gallium 68 PSMA-11 more available. According to the Prostate Cancer Foundation, “The kits will be distributed to a network of radiopharmacies that can manufacture 68Ga-PSMA-11, located across the country. From there, it will be delivered for use in PET imaging centers.” This is good news for PCa patients, especially those diagnosed with higher risk PCa who need to have advanced disease ruled in or out. The same principle of binding radioactive isotopes to PSMA can be applied to destroy PCa cells. On Mar. 23, 2022 the Swiss pharmaceutical company Novartis announced that the FDA had approved their targeted radioligand therapy for metastatic PCa. It’s called PluvictoTM (lutetium Lu 177 vipivotide tetraxetan) (formerly referred to as 177Lu-PSMA-617), and it’s the first such treatment to be approved by the FDA. It’s barely 3 years since we posted our original PSMA blog, and there are now 2 approved agents, 1 approved kit, and the first approved radioligand therapy. How’s that for progress?
Finding out that you have prostate cancer (PCa) is never good news. However, the blow is softened when your doctor assures you that it is early, slow-growing, and confined to the gland (localized). In such cases, statistics show a 15-year survival rate of 96%.[i] However, there is no treatment that comes with a 100% guarantee of freedom from recurrence. There is always a chance—however small—that the disease will come back, even for men with low risk PCa. Unfortunately, greater risk comes with higher recurrence rates.
Prostate specific antigen (PSA)
Prostate cancer comes with a built-in biochemical “communication device” called the PSA blood test. PSA stands for Prostate Specific Antigen, a surface protein on all prostate cells that is released into the blood stream in measurable amounts. As long as the prostate gland remains in the body, it will continue to release PSA. In fact, any activity that stimulates the gland can raise the amount of PSA in the blood. Here are just a few things that can elevate the PSA:
- Infection or inflammation in the gland
- Benign prostatis hyperplasia (BPH, a normal aging-related gland enlargement)
- Prostate cancer
- Digital rectal exam (DRE)
- Sexual activity
- Even something as ordinary as riding a bike
As you can see, a higher-than-usual PSA can mean a lot of different things, not just prostate cancer. But it’s important to remember that just as healthy prostate cells have PSA, so do prostate cancer cells. Why? Because they are still prostate cells, only mutated.
PSA can indicate prostate cancer recurrence
However, there is one situation in which a rising PSA can only mean that prostate cancer is back after treatment. When the prostate gland is completely removed (radical prostatectomy), radiated or ablated, it’s called radical treatment (radical = total). When radical treatment is successful, there are no more functional prostate cells. Therefore, it is expected that within a short time after radical treatment, a man’s PSA will be undetectable. No prostate cells, no PSA. No prostate cancer cells, no PSA. This is why a man must have an annual PSA test after PCa treatment. It’s a safety check to make sure that the “communication device” is on “radio silence.”
However, a detectable PSA after radical treatment is the first blip on the PCa radar screen. Before setting off an alarm, it’s normal to repeat the PSA test within a few weeks or months. If it is still detectable, or even a little higher, there is a suspicion that PCa is back. This is called biochemical recurrence because PSA is a “biomarker” for PCa recurrence. But the most important question is, Where is it? Before sending in a SWAT team, the medical detectives have to pin down the location.
There is a powerful new tool for identifying even very early, tiny PCa recurrence called PSMA-PET scan. PSMA, or Prostate Specific Membrane Antigen, is different from PSA, and is more indicative of prostate cancer cells. In fact, PSMA helps the cancer cells get the nutrients they need to fuel their growth. Learn more details about this at my looking for a needle in a haystack blog.
The new type of imaging called PSMA-PET uses radioactive tracers that are “tagged” onto molecules that trick PSMA into binding these molecules onto individual cancer cells. This makes the cells “light up” during the scan. Even a very small cluster (pre-tumor) of PCa cells will show up, whether they are in the prostate bed, nearby lymph nodes or bone, or even remote locations such as another organ or different part of the skeleton. The sooner a recurrence is detected and identified, the more quickly a potentially curative plan can be put into place.
The future for PSMA-PET
PSMA-PET has been more available in Europe, but the number of U.S. centers is growing. I invite you to watch a good 12-minute video interview with an Italian expert, Stefano Fani, who offers encouraging news about PSMA-PET and how it applies to locating biochemical recurrence. He assures us that it is “simple, fast, patient-friendly…and very accurate.” There are other imaging uses as well, such as staging metastatic disease.
Even more exciting is what is called theranostic medicine. In an age of increasingly personalized medicine, the ability to use a technology like PSMA-PET to deliver a cancer-killing agent directly to the cell by disguising it as a desirable nutrient for PSMA to bind to the cell (think of the Trojan Horse) offers hope for developing treatments for recurrent PCa that were unheard of until only recently.
While the future is incredibly promising, it’s important to keep in mind that, as with all imaging technologies, there is a learning curve. Dr. Fani points out that certain body conditions such as inflammation in the lungs from chronic smoking may also attract the tagged molecules and be mistaken for recurrent PCa on the scan. Thus, experience matters, as does being trained by an expert.
Similarly, multiparametric MRI (mpMRI) of the prostate has become more widely available in the U.S. but here too experience matters. The Sperling Prostate Center is proud to be a globally recognized leader in using our powerful 3 Tesla (3T) magnet in the hands of our expert team. Whether it’s mpMRI for detection of suspected PCa, or PSMA-PET for identifying recurrence, entrusting your prostate health to top authorities is a wise investment.
[i] https://www.webmd.com/prostate-cancer/prostate-cancer-survival-rates-what-they-mean#1NOTE: 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.