Sperling Prostate Center

Should We Use PSMA/PET Sooner in the Diagnostic Pathway?

One of the most exciting developments in the world of prostate cancer (PCa) diagnosis is PSMA-based imaging. PSMA, or prostate specific membrane antigen, is abundant on the surface of PCa cells, so it’s better than the conventional PSA (prostate specific antigen) blood test for detecting PCa. In fact, a type of nuclear medicine imaging called a PET (positron emission tomography) scan can make terrific use of PSMA for detecting PCa.

As I wrote in a previous 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.

You might wonder why, if it’s so great, it isn’t routinely used before biopsy when a man’s PSA blood test comes back suspicious for PCa?

PSMA-PET not routinely used

Currently, PSMA-PET use is not common when patients are diagnosed with low-to-intermediate risk PCa. Instead, it is mostly limited to two high-risk situations:

  1. When a newly diagnosed patient has a high PSA, high Gleason score, bulky tumor seen on MRI, and/or any symptoms such as bone pain or blood in urine, he is suspected of already having advanced or metastatic disease. In this case, PSMA-PET is used to determine PCa locations outside the prostate gland.
  2. When a patient has already been treated with either surgery, radiation, or a combination—or is already on androgen deprivation therapy (ADT)—and his PSA is beginning to rise, he is suspected of having recurrence either at the treatment site or more remotely.

In either case, the scan results give key information for planning aggressive treatment, and Medicare has approved coverage in these situations. It’s no wonder, since patients with advanced or metastatic PCa, PSMA-PET is shown to reduce treatment costs and extend life, thanks to better informed treatment strategies. Besides radiation, chemotherapy and immunotherapy drugs, there are even new treatment approaches that take advantage of PSMA to target and deliver nuclear isotopes to individual PCa cells.

Reluctance to use PSMA-PET scan during early diagnosis

Cost is the main reason why PSMA-PET is not usually employed when a patient is first diagnosed with early, low-risk PCa. PSMA-PET is expensive compared to Multiparametric MRI (mpMRI), which is excellent for detecting clinically significant PCa and guiding targeted biopsies for minimalist diagnosis. There are other reasons some doctors are cautious about prescribing PSMA-PET. A JAMA article cautions,

PSMA PET scans are not perfect. There is a small chance of a missed diagnosis because a small percentage of prostate cancers do not express PSMA and cannot be detected by a PSMA PET scan. Sometimes, PSMA is expressed by other types of cancer and by noncancer-related conditions, which may be incorrectly diagnosed as prostate cancer. Though rare, a missed diagnosis or an incorrect diagnosis can lead physicians to offer an inappropriate treatment.[i]

Should we be using PSMA-PET scans during early diagnosis?

At present, most experts agree that mpMRI is preferred during the diagnostic pathway for early stage, low-risk disease. However, some clinicians are suggesting that PSMA should also be used. A 2021 Australian study of 291 men suspected of having PCa but no prior biopsy found best results when both imaging modalities were used with.[ii] The researchers noted:

The combination of magnetic resonance imaging (MRI) + prostate-specific membrane antigen positron emission tomography reduces false negatives for clinically significant prostate cancer (csPCa) compared with MRI, potentially allowing a reduction in the number of prostate biopsies required to diagnose csPCa.

Dialogue and debate continue, as various combinations and results are studied. According to a 2022 Urology Times news article, National Institutes of Health expert Dr. Peter Pinto remarked, “PSMA has an opportunity to potentially delineate areas of the prostate where the MRI can miss cancer. We know there is no perfect imaging modality that has 100% specificity and 100% sensitivity. So to layer in a PET scan like PSMA with MRI has the potential to find additional tumors [but] until we have definitive clinical trials that show this, we cannot assume that’s the case.”

On the other hand, a 2022 news report on an Australian comparison study of MRI vs. PSMA-PET said the researchers found MRI still superior for detecting clinically significant PCa. Co-author Lih-Ming Wong is quoted as stating, “Our analysis found that MRI scans were better than PSMA-PET for detecting any grade of prostate cancer.” However, he added, “Even with fine-tuning, we suspect PSMA PET/CT won’t replace MRI as the main method of prostate cancer detection. But it likely will have application in the future as an adjunct to the MRI, or for people for whom an MRI is unsuitable, or as a single combined ‘diagnostic and staging’ scan for appropriately selected patients.”

Thus, it appears the jury is still out regarding use of PSMA-PET sooner in the PCa diagnostic pathway. We’ll be keeping an ear to the ground for future results.

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] Kwon DH, Velazquez AI, de Kouchkovsky I. PSMA PET Scan. JAMA Oncol. 2022;8(12):1860.
[ii] Emmett L, Buteau J, Papa N, Moon D et al. The Additive Diagnostic Value of Prostate-specific Membrane Antigen Positron Emission Tomography Computed Tomography to Multiparametric Magnetic Resonance Imaging Triage in the Diagnosis of Prostate Cancer (PRIMARY): A Prospective Multicentre Study. Eur Urol. 2021 Dec;80(6):682-689.


About Dr. Dan Sperling

Dan Sperling, MD, DABR, is a board certified radiologist who is globally recognized as a leader in multiparametric MRI for the detection and diagnosis of a range of disease conditions. As Medical Director of the Sperling Prostate Center, Sperling Medical Group and Sperling Neurosurgery Associates, he and his team are on the leading edge of significant change in medical practice. He is the co-author of the new patient book Redefining Prostate Cancer, and is a contributing author on over 25 published studies. For more information, contact the Sperling Prostate Center.

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