Another Option for Metastatic Prostate Cancer

DARRELL WILSON HAS RECEIVED nearly every type of available treatment for metastatic prostate cancer. Since his diagnosis in 2009, the 74-year-old veteran and former banker, who lives in Boise, Idaho, has undergone chemotherapy, multiple types of hormone-deprivation therapy, immunotherapy and a kind of radiation called brachytherapy that uses tiny radioactive seeds implanted directly in the prostate.

As an advocate both for himself and other patients with prostate cancer, Wilson prides himself on being aware of new treatment developments. So he had already heard about the injectable targeted radiation called Pluvicto (lutetium Lu-177 vipivotide tetraxetan) when his urologist mentioned it in the spring of 2024. The Food and Drug Administration (FDA) first approved Pluvicto in 2022 to treat certain people who had metastatic prostate cancer that had progressed after the use of chemotherapy and hormone-deprivation therapy.

The drug’s approval provided another treatment option for people like Wilson who have metastatic prostate cancer, but it also heralded a new, targeted way to treat cancer, using radiation on a tiny scale. Called radioligand therapy, Pluvicto uses a ligand to find prostate-specific membrane antigen (PSMA), a protein that is highly expressed in 90% of metastatic prostate cancer cells. The ligand delivers radioactive particles, called lutetium-177 (Lu-177), directly to the cancer cell.

“It’s like a pickup truck,” Wilson says. “You’ve got this ligand pickup truck, and it goes and finds the PSMA. Its cargo is the radiation, which goes into the cell and hopefully damages it enough that it can’t reproduce, and maybe it even dies.”

A Starting Point

The phase III clinical trial that led to Pluvicto’s initial FDA approval included 831 men who had PSMA-positive metastatic prostate cancer that had stopped responding to chemotherapy and androgen-deprivation therapy. In the trial, one group of people received standard-of-care therapy, which could include hormone therapy and radiation at their doctor’s discretion. The other group received standard-of-care treatment plus Pluvicto. In the Pluvicto group, the median overall survival was 15.3 months, compared with 11.3 months in the standard care group. People who took Pluvicto also experienced, on average, an extension of more than five months of progression-free survival, which was defined as the amount of time a person was alive and had no tumor progression based on imaging scans.

While metastatic prostate cancer remains incurable, PSMA-targeted therapy offers another option for those with advanced disease, says medical oncologist Praful Ravi at Dana-Farber Cancer Institute in Boston. “I view it as a tool in the toolbox, but it’s not going to knock this out, at least in the advanced setting,” he says. When advanced prostate cancer doesn’t respond to existing treatments, a new class of drug is likely to be more effective than going back to the same treatments, Ravi says. “By and large, we have three buckets of therapies for advanced prostate cancer,” he says. “We have the hormone bucket. We have the chemotherapy bucket. And now we have the radioligand bucket.”

The treatment represents what’s called a theranostic approach, which pairs diagnostics with therapeutics. Prior to treatment, people with metastatic prostate cancer have a specialized PSMA- PET scan, which uses a radioactive tracer to confirm the prostate cancer cells express PSMA. Then patients who have PSMA-positive prostate cancer go on to receive an injection that delivers targeted radiation directly to the cancer cells. In this case, Pluvicto uses a ligand that can find and attach to the PSMA proteins on cancer cells and then delivers lutetium-177 to the tumor tissues.

The development of this approach to target PSMA stretches back to 1987, when researchers first reported finding PSMA on the surface of prostate cancer cells. In 1996, the FDA approved a new imaging method that used an antibody—one identified in the 1987 study—to bind to PSMA on the surface of prostate cancer cells. However, that antibody only attached to dead or dying cells, which meant that this new imaging method was limited in its usefulness.

In time, researchers learned more about ways to locate cancer using PSMA-targeted ligands and how to harness those ligands for both imaging and treatment. In 2012, researchers reported that a small molecule could transport radioactive gallium to PSMA and illuminate cancer cells on PET scans. As a diagnostic tool for metastatic diseases, these scans were more sensitive than the bone scans and CT scans that were commonly used to look for metastatic growth. In 2020, the FDA approved gallium-based PSMA-PET scans to look for suspected new growth in previously treated patients with elevated PSA levels. Gallium delivers enough radiation to light up a PET scan but not enough to critically damage cancer cells.

Researchers also have conducted clinical trials on another ligand, called PSMA-617, which closely binds to PSMA on cancer cells to deliver lutetium-177—the radioactive agent used in Pluvicto.

Weighing the Risks

By the time he was first offered Pluvicto in the spring of 2024, Wilson was well-acquainted with the various treatments and the diminishing effects of multiple regimens. He’d also learned, right from the start of his own journey, the importance of following new research and advocating for himself.

In 2009, after periodic blood tests showed that his PSA had risen above 3 ng/ml, his first provider dismissed the need for a biopsy. Wilson insisted on one. His PSA had been “bouncing around between 4 and 5,” he says. He pointed out that the National Comprehensive Cancer Network, a nonprofit that offers cancer-related treatment and screening guidelines, encourages physicians to discuss the option of a biopsy when patients have PSA levels above 3 ng/ml.

After being diagnosed with high‑risk early-stage prostate cancer, Darrell Wilson learned in 2015 that his cancer had metastasized. The 74-year-old veteran and former banker started PSMA-targeted therapy in March 2025. Photo courtesy of Darrell Wilson

Pathologists “grade” prostate tissue based on the abnormality of the most common types of cells found in the biopsy tissue, producing a Gleason score. When Wilson received his biopsy results, his Gleason score was 8, which suggests the presence of highly abnormal cancer cells. In plain terms, it meant that his prostate cancer was at high risk of growing quickly and metastasizing, even though he didn’t have any evidence of metastatic disease.

In the fall of 2009, he was treated with intensity-modulated radiation therapy, or IMRT, which uses multiple beams of radiation from different angles to target the tumor. The treatment was taxing but effective in shrinking the tumor to the point where it was not visible on scans. At the time, he lived in coastal California, and his treatment center was a three-hour drive away. To complete the seven-week course of radiation, he and his wife packed up their RV and temporarily moved to the San Francisco Bay Area. At the same time, he began receiving androgen-deprivation therapy, which cuts off the body’s production of testosterone to starve the tumor.

“Between the two [treatments],” Wilson says, “it was beating me up with fatigue.”

His providers checked his PSA level about every three months. In 2013 and 2014, his PSA started rising, so he underwent brachytherapy, an uncomfortable procedure that involves inserting tiny needles loaded with radioactive seeds into a person’s perineum. In November 2015, MRI and bone scans showed that his prostate cancer had spread to his lymph nodes, hip and shoulder blade. “That made me angry,” he says. “I’d done everything they told me to do, and they’d always indicated the odds were in my favor.”

He found a support group that included people with advanced prostate cancer, which he says helped him get through the emotional and psychological stress of a diagnosis of metastatic disease. “All of a sudden, I felt like, ‘OK, there are other people going through this kind of stuff,’” he says. Within two years, he was leading the group. Soon, he started a new support group for men with advanced prostate cancer closer to his home in California.

A series of treatments followed. By 2017, he was receiving injections of Lupron (leuprorelin), another kind of testosterone-suppressing hormone therapy, which kept his PSA levels stable for two years, but his numbers started to rise again. He began treatment with a new FDA-approved hormone-deprivation therapy called Zytiga (abiraterone) in 2019, and it controlled his cancer and kept his PSA levels low for more than three years.

In 2020, he moved to Boise and started a new support group while virtually leading the support group he left behind in California. In 2022, when his PSA levels began to rise, his urologist suggested the immunotherapy drug Provenge (sipuleucel-T), which had little effect. In 2023, he had his first PSMA-PET scan—which showed new growth in his bones. He switched to a different testosterone suppressant and received six cycles of treatment with the chemotherapy docetaxel. “It left me very tired,” he says. “My summer was ruined with fatigue.”

When his PSA numbers rose again in the spring of 2024, Wilson wasn’t interested in taking Pluvicto. It consists of up to six infusions, each lasting about 10 or 15 minutes, spaced six weeks apart. The treatment itself, says Wilson, isn’t particularly painful, but the precautions and follow-up are inconvenient.

“Afterward is a nuisance,” Wilson says. For three days, the treated person must sleep away from others and use a separate bathroom to avoid exposing other people to radioactive substances, which could put them at risk of getting sick. “I didn’t want to ruin my summer again,” he says. Plus, “that makes it hard to lead groups or even go shopping.”

In the early months of 2025, though, PSMA-PET scans showed new growth in his lungs. Other metastases had grown, and cancerous cells were found in additional lymph nodes. That convinced Wilson to start taking Pluvicto, which he began on March 10, 2025. When he started taking it, his side effects were dry eyes and a dry mouth. These are the most common side effects, along with fatigue, that patients report, says Ravi at Dana-Farber, who notes that salivary glands and tear ducts have cells with PSMA and may be damaged during treatment.

Some people with metastatic prostate cancer will not be eligible to take Pluvicto because their tumors do not express PSMA. And the treatment, if it provides a benefit, does so for only some time. “Many patients, if not all patients, will eventually progress,” says Andrea Miyahira, who is the senior director of global research and scientific communication at the Prostate Cancer Foundation, a nonprofit advocacy organization.

Still, people with metastatic prostate cancer who took Pluvicto in the study did see some survival benefit compared with standard care. “People who took it lived longer on average than those who didn’t,” says Ravi, “and it’s a class of therapy that your cancer has not seen before.”

In March 2025, the FDA approved Pluvicto for people with metastatic prostate cancer who haven’t yet undergone chemotherapy but whose cancer had progressed after androgen-deprivation therapy. The extended approval expands the number of men who are eligible for the treatment and might want to avoid chemotherapy. The use of radioligand therapy could one day be useful to others, says Ravi, such as those with high-risk localized prostate cancer or who have metastatic prostate cancer that is still responding to hormone therapy.

Improving Treatment Approaches

Researchers continue to study other ways to deliver radioligand therapy—looking for potential targets in tumors and new delivery methods and types of radioactive particles. They’re also looking for better ways to understand which people are most likely to benefit.

There have been ongoing signs of promise: A case study published in 2016 by researchers in Germany found that two patients with metastatic prostate cancer had experienced a full remission after being treated with a different kind of radiation called alpha delivered by a PSMA-targeting ligand. Alpha emitters have higher energy and a shorter range, which means they can deliver more radiation and inflict more damage to cancerous growths than beta radiation—which is used by Pluvicto—while sparing surrounding tissue. “Those results made the whole field excited,” says Miyahira, who also cautions that the case study looked at two patients, as opposed to a clinical trial with many individuals.

“There are many, many trials looking at PSMA now,” says Ravi. “They’re looking at targeted agents all across the disease spectrum and not just in the advanced setting.” Some studies are looking at how to combine radioligand therapy with other treatments; others are looking for genetic biomarkers that can identify patients most likely to benefit from the approach. Some researchers say it’s worth investigating whether Pluvicto or other radioligand therapies might be useful in earlier stages of disease. “There is a feeling in the community that the treatment is likely to work better earlier, but we need data from trials to bear that out,” Ravi says.

Wilson, in Boise, has never participated in a clinical trial, but he’s open to joining one. “It’s exciting to know that there are more coming,” he says. Keeping up with clinical trials can help guide him to new treatment options, he says. He recommends that people diagnosed with metastatic prostate cancer become familiar with treatment guidelines and review them during conversations with their urologist or oncologist. “You really need to be your own advocate,” he says.

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