What Is PSMA Therapy for Metastatic Prostate Cancer?
Published on September 16, 2026
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A metastatic prostate cancer diagnosis, which occurs when the cancer spreads beyond the prostate to other parts of the body, can feel scary and overwhelming. But new, targeted forms of treatment are available, and they are transforming the landscape of prostate cancer care.
One of these newer treatments is called prostate-specific membrane antigen (PSMA) therapy, which targets and attacks prostate cancer cells anywhere in the body, while minimizing the harm done to healthy tissue. While this treatment doesn’t cure metastatic prostate cancer, research has found that it can significantly slow disease progression, extending survival and improving quality of life.
What Does It Mean to Be PSMA-Positive?
PSMA is a type of protein found in large amounts on the surface of most prostate cancer cells. “Over 90 percent of prostate cancers express PSMA,” says Amir Iravani, MD, a nuclear medicine physician with UCLA Health in Los Angeles. “That makes PSMA a very appealing target [for treatment].”
If your cancer is PSMA-positive, it means that the prostate tumor cells in your body are over-expressing PSMA, and you may be a candidate for PSMA-targeted therapy. But the full story is a little more complicated than that.
Despite its name, PSMA is not actually specific to prostate tissue, and it can normally be found in the small intestines, liver, kidneys, salivary glands, and various other tissues throughout the body. It’s also found in other types of cancer.
“In a way, I would say almost all tumors are ‘PSMA-positive,’” says Scott Tagawa, MD, a professor of medicine and urology at Weill Cornell Medicine. But Dr. Tagawa notes that PSMA-positive is “not really a medical term” — it’s a regulatory term used specifically in diagnosis and treatment.
Providers check for PSMA status with a specialized imaging test called a PSMA PET scan. Positron emission tomography (PET) scanners detect cancers using a radiotracer, a radioactive material that binds to target cells and emits a tiny amount of radiation that “lights up” on imaging scans. The PSMA PET radiotracer, called piflufolastat F-18, binds to the PSMA on cells. Prostate cancer cells typically have more of the protein — and light up more in the scans — than other tissues.
To be PSMA-positive, then, at least one of your metastatic tumors must light up brighter than the liver, a reference organ, on the PSMA PET scan, Dr. Iravani says.
How PSMA Therapy Works
PSMA therapy falls under the category of “theranostics,” a new oncology paradigm combining “therapy” and “diagnostics.” This means that the same type of process used in diagnostics is also used in treatment. In other words, PSMA therapy is similar to PSMA PET imaging, just with a different type of radiation that can damage cells.
PSMA therapy, also called PSMA-targeted radioligand therapy, uses a small molecule called a ligand to bind to the PSMA on cells. Attached to this ligand is a radioactive isotope called lutetium-177, which releases once the ligand latches to the protein, delivering small doses of cancer-killing radiation exactly where it’s needed most.
This precision sets PSMA therapy apart from other, broader cancer treatments like external-beam radiation therapy (EBRT) and standard chemotherapy. EBRT directs high-energy radiation beams from a machine outside the body to a specific, targeted area, damaging both cancerous and healthy tissue. Chemotherapy, on the other hand, travels through the bloodstream to damage fast-dividing cells throughout the body, cancerous and healthy alike.
PSMA therapy can also damage healthy tissue because some noncancerous cells in the body express PSMA, but this harm is minimal, and unlike EBRT and chemo, it doesn’t typically cause significant side effects. “The amount of PSMA expression determines how much radiation is going to be delivered,” Iravani says. “At the same time, normal tissues tend to clear PSMA faster than tumor tissues because the tumor tissues hold on to the compound.”
Daniel Sentana Lledo, MD, a medical oncologist with the Dana-Farber Cancer Institute, believes that “this is only the beginning of a revolution in how we treat cancer.”
Future therapies may make this type of treatment even safer by using a different target protein than PSMA or a different radiation molecule, he says. “This is a field that is rapidly growing, and in many ways, it’s the future of oncology. There are many other therapeutic classes out there, and I think this is the first of many compounds.”
Who Is Eligible for PSMA Therapy?
Lutetium Lu-177 vipivotide tetraxetan (Pluvicto) is the only PSMA-targeted radioligand therapy approved by the U.S. Food and Drug Administration (FDA) for prostate cancer. It’s currently approved for people with PSMA-positive metastatic prostate cancer, when used in combination with hormone therapy. “It’s almost a first-line treatment,” Iravani says.
To be eligible for this therapy, you first need positive results on a PSMA PET scan. Then, Tagawa says, providers may “think twice about” (but not necessarily rule out) giving this treatment to people who have:
- Kidney failure, because the drug is metabolized by the kidneys
- Severe dry mouth, because dry mouth is also a common side effect and may make swallowing food very difficult
- Low blood cell counts, because this drug can further decrease blood counts
Your healthcare provider will review your medical history and diagnosis with you to determine whether PSMA therapy is right for you.
What to Expect During Treatment
PSMA therapy is administered through an intravenous (IV) infusion, typically once every six weeks, for up to six doses. The entire visit — including a health checkup beforehand and a waiting period after the infusion — may take less than an hour, with the actual infusion usually lasting about 10 minutes.
You will have to follow some safety precautions for the first week after each infusion to limit radiation exposure to people around you, such as staying at least three feet away from others for the majority of the time, sleeping alone, and practicing good hygiene.
Common side effects from the treatment include:
- Dry mouth
- Fatigue
- Gastrointestinal issues like nausea, appetite loss, and constipation
- Joint or back pain
- Low blood counts
Overall, the therapy is pretty well-tolerated, Dr. Sentana Lledo says, with a caveat being that you may need urgent medical attention if your blood counts drop too low. This can present as fatigue, shortness of breath, and lightheadedness if your red blood cells drop (anemia); easy bruising and bleeding if your platelets drop; and fever and chills, mouth sores, and sore throat if your white blood cells drop.
Call your provider if you experience any of these symptoms or “something really out of the ordinary,” Sentana Lledo says, like uncontrolled nausea or vomiting or severe dehydration.
Resources We Trust
- Cleveland Clinic: Why You Might Need a PSMA PET Scan for Advanced Prostate Cancer
- Mayo Clinic: The Mayo Clinic Way of Advanced Prostate Cancer Treatment
- International Atomic Energy Agency: What Are Radiopharmaceuticals?
- Dana-Farber Cancer Institute: 5 Things to Know About Radioligand Therapy
- Society of Nuclear Medicine & Molecular Imaging: Fact Sheet: Radiopharmaceutical Therapy and Prostate Cancer
EDITORIAL SOURCES
Everyday Health follows strict sourcing guidelines to ensure the accuracy of its content, outlined in our editorial policy. We use only trustworthy sources, including peer-reviewed studies, board-certified medical experts, patients with lived experience, and information from top institutions.
Resources
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- Mitteldorf D. PSMA Imaging and Radioligand Therapy in Prostate Cancer: A New Era in Detection and Treatment. Cancer Academy. February 4, 2025.
- Kishan A et al. Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent Prostate Cancer (LUNAR): An Open-Label, Randomized, Controlled, Phase II Study. Journal of Clinical Oncology. November 12, 2025.
- Jochumsen MR et al. PSMA PET/CT for Primary Staging of Prostate Cancer – an Updated Overview. Seminars in Nuclear Medicine. December 6, 2023.
- Pluvicto. San Antonio Cancer Center.
- Scanlan K et al. PSMA and Salivary Glands – a Primer for Residents and Nuclear Medicine Physicians. The Journal of Nuclear Medicine. June 2025.
- DePalatis L et al. Applications of PSMA-PET in tumors other than prostate cancer. Nuclear Medicine. January 1, 2022.
- PET Scan. Cleveland Clinic. April 14, 2026.
- PSMA PET Imaging for Prostate Cancer. UChicago Medicine.
- Expanding Cancer Treatment With Theranostics. Cleveland Clinic.
- Gregory SY. PSMA-targeted therapy: How are radiopharmaceuticals used to treat advanced prostate cancer? Mayo Clinic. January 21, 2026.
- External Beam Radiation for Prostate Cancer. Mayo Clinic. July 26, 2026.
- FDA Approves Lutetium Lu 177 Vipivotide Tetraxetan With Androgen Receptor Pathway Inhibitor Therapy for Metastatic Androgen Pathway Modulation-Naïve or -Sensitive Prostate Cancer. U.S. Food and Drug Association. July 31, 2026.
- Stallard J. FDA Expands Approval of Pluvicto for Metastatic Prostate Cancer: Targets a Protein Called PSMA. Memorial Sloan Kettering Cancer Center. August 14, 2026.
- What to Expect With Pluvicto Treatment. Pluvicto.
- Pluvicto. Florida Cancer Specialists & Research Institute.
- Lutetium Lu 177 Vipivotide Tetraxetan (Pluvicto). UW Health.
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