Understanding PSMA: What Patients Facing Prostate Cancer Should Know

Overview

“When we speak with patients facing late-stage prostate cancer,” reflects Dr. Babak Saboury, MD, MPH, DABR, DABNM, Co-Founder and Chief Innovation Officer of United Theranostics, “we’re often struck by how many of them already understand what PSMA is.”

The internet has aided patients in preparing for these and other medical conversations for many years, and while many find excellent sources on their own, it’s still common for patients to arrive with misconceptions about how the antigen works, and how it pairs with radiopharmaceuticals to identify and treat prostate cancer.

“The name itself — prostate-specific membrane antigen — is part of the confusion,” Dr. Saboury explains. “It can be found in many other places in the body besides the prostate.” In fact, the protein appears in low levels in normal tissue throughout the small intestine, kidneys, salivary glands, liver, and elsewhere.

What Does PSMA Do?

Evidence suggests PSMA contributes to the breakdown of folates, which is a critical step in how cells build DNA and replicate. While that’s an essential part of normal cell division, it’s also one of the reasons some prostate tumors grow and spread so quickly.

Why PSMA Matters in Prostate Cancer Treatment

PSMA was first identified in 1987. But it took 35 years (until 2022, with the FDA approval of Pluvicto) for the first PSMA-targeted radioligand therapy to reach patients.

These therapies are possible because PSMA uptake is significantly higher in prostate cancer cells than almost anywhere else in the body. A 2010 study estimated PSMA expression in prostate cancer cells can reach 100 to 1,000 times the levels seen in normal cells. As with most things in cancer, though, this isn’t a universal rule: an estimated 7–10% of prostate cancers show very low essentially no PSMA expression.

What makes PSMA useful for treatment is that it attracts specific small molecules that can be paired with small amounts of radioactive material. When these molecules are bonded to that radioactive material, the combination is called a radiopharmaceutical. When the same approach is used to track how the body functions, the radioactive compounds are called radiotracers.

“When these radiotracers flow through the body, they concentrate inside cells containing their target, which is, in this example, PSMA” elaborates Dr. Saboury, “and gives Nuclear Oncologists the opportunity to identify, measure, and even treat prostate cancer with the same molecular signal.” Other targets and tracers have been used in nuclear medicine for nearly a century, but PSMA is one of the most promising tools in the fight against prostate cancer identified to date.

PSMA’s Importance in Medical Imaging

When a radiotracer binds to a PSMA protein, it gives Nuclear Medicine Physicians a unique opportunity for precision: imaging detailed enough to map the cancer at the molecular level. PSMA imaging doesn’t just show cancer within the prostate. It can also reveal whether the cancer has spread to lymph nodes, bone, or other tissues throughout the body, often catching disease that wasn’t detectable only a few years ago.

The same phenomenon makes PSMA powerful for treatment. Beyond targeting the cancer, PET/CT and SPECT/CT scans taken during the course of treatment let Nuclear Oncologists see how doses are working, adjust the next dose, or change the treatment plan in real time. Utilizing the resulting images to personalize the radiopharmaceutical therapy and measure the dose of radiation that reaches the tumors and various tissues (called dosimetry) has given nuclear medicine physicians like Dr. Saboury the ability to personalize and adjust doses according to the needs of each patient, which is a particular specialty of United Theranostics, and is less widely available elsewhere.

PSMA and Treatment: The Therapeutic Side

“The same vehicle we use to identify cancer cells can be retooled to deliver treatment to those same cells, while minimizing exposure to surrounding healthy tissue,” Dr. Saboury explains. “That is the heart of theranostics.”

This is the operating mechanism behind Pluvicto and the broader class of radiopharmaceutical therapies, including many others that may be available through current United Theranostics clinical trials.

Can PSMA Expression Change over time?

While roughly 90% of prostate cancer patients show high PSMA expression, evidence suggests that expression isn’t fixed. “Not only can PSMA expression change over time, but there’s ample research showing that other treatments can lower it,” Dr. Saboury notes, citing chemotherapy and some hormone therapies as examples. “And as cancer spreads or metastasizes, some studies show that PSMA expression can be significantly lower in those new locations.”

What your PSMA PET results mean for your treatment plan

For metastatic castration-resistant prostate cancer, PSMA PET scan results may, among other factors, indicate eligibility for treatments like Pluvicto (Lu‑177 PSMA‑617), or one of several other radiopharmaceuticals currently being studied in clinical trials. High PSMA expression alone doesn’t automatically make someone a candidate for these therapies, so it’s important to talk through the full picture with your care team, ideally including a Nuclear Oncologist who specializes in this work.

If your PSMA PET results come back low, current PSMA-targeted therapies are unlikely to work, as the radiotracers won’t be able to bind to, image, or treat lesions effectively. “In that scenario, your oncologist will typically point you toward other options: hormone therapies, chemotherapy, other targeted agents, or bone-targeting agents like Xofigo,” Dr. Saboury explains.

Questions to ask about PSMA

If you’re curious about PSMA and what it might mean for your treatment, consider asking your care team a few of these questions:

• Am I a candidate for a PSMA PET/CT scan?
• Based on my PSMA expression, could PSMA-targeted therapy be an option for me?
• Is Pluvicto something we should consider now, or later in my treatment course?
• Are there PSMA-related clinical trials or others that I should know about?

Conclusion

PSMA gives Nuclear Medicine Physicians a remarkably clear view of how prostate cancer responds to therapy, and powers some of the most precise treatments available today, while minimizing damage to surrounding tissue compared to treatments like chemotherapy.

Targeted radiopharmaceutical therapy paired with precision molecular imaging is the singular focus of each United Theranostics center. We work alongside our patients’ existing care teams to deliver theranostic treatments in patient-centered, outpatient environments outside of large hospital systems. United Theranostics also offers access to a wide range of radiopharmaceutical clinical trials that may not be available elsewhere.

Find the United Theranostics location nearest you, or connect with one of our representatives to discuss whether PSMA-targeted therapy may be right for you.

This article is for informational purposes only and does not constitute medical advice. Please consult with your physician or a qualified healthcare provider regarding your individual treatment options.