Researchers from UCLA have found a promising new way to help men with recurring prostate cancer live longer without their disease getting worse.
In a recent clinical trial, adding a targeted radiation drug before standard treatment more than doubled the amount of time patients remained free of cancer progression.
The study, presented at the 2025 American Society for Radiation Oncology meeting in San Francisco, involved 92 men whose prostate cancer had returned after initial treatment.
This type of recurrence, called oligorecurrent disease, shows up as just a few new tumors and can often be treated with a type of focused radiation therapy known as SBRT (stereotactic body radiotherapy).
In this trial, one group of men received SBRT alone. The other group received two doses of a special radioactive drug called 177Lu-PNT2002 before their radiation.
This drug is designed to target a protein on prostate cancer cells called PSMA and deliver radiation directly to those cancer cells—even the ones too small to be seen on scans.
The results were impressive. Patients who received the radioligand drug plus SBRT went a median of 17.6 months without disease progression, compared to just 7.4 months for those who received SBRT alone. That’s a 63% reduction in the risk of the cancer coming back, needing hormone therapy, or dying.
Importantly, patients who got the drug also delayed needing hormone therapy by 10 months longer than those who only had SBRT. Hormone therapy, while helpful, comes with serious side effects like fatigue and bone thinning. Delaying it can greatly improve quality of life.
Dr. Amar Kishan, lead author of the study and a professor at UCLA, said this is the first randomized trial to prove that adding a PSMA-targeted radioligand drug to radiation therapy can meaningfully delay cancer progression. “It gives patients more time before they need hormonal treatment, which is a big deal for their well-being,” said Kishan.
The treatment was well tolerated, with few side effects. It also worked across all patients, no matter how many tumors they had or what stage they were in. The team used advanced imaging called PSMA PET to guide radiation, helping ensure they treated all visible tumors, while the radioactive drug helped attack the invisible ones.
In addition to showing clear clinical benefits, the researchers found biological clues that might help predict who will respond best to this treatment. For example, patients whose immune systems responded strongly after radiation tended to do better. They also identified a set of 20 genes that may be linked to higher or lower risk of progression.
Even though the combination worked well, about 64% of patients still saw their cancer return, showing that treating invisible disease remains a big challenge. Still, the researchers say this is a major step forward.
“This is proof we can intervene earlier with radioligand therapy and really change the course of prostate cancer,” said Kishan. He and his team are planning more research to see how long these benefits last and how the treatment can be improved even further.
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