Adding Radiopharmaceutical to Stereotactic Radiation Improves Outcomes in Patients with Limited Metastatic Prostate Cancer

A new study shows that men with a limited number of prostate cancer metastases lived longer without their cancer progressing when they received a radiopharmaceutical drug before targeted radiation. Results from the phase II LUNAR trial were presented today at the 2025 ASTRO Annual Meeting.

“This approach lets us pair radiation aimed at tumors we can see with a radiopharmaceutical that reaches microscopic disease we can’t see,” said Amar U. Kishan, MD, principal investigator and professor of radiation oncology at UCLA. “Patients experienced a notably longer interval before progression.”

The trial included 92 men with recurrent prostate cancer that had spread to one to five sites. Patients were randomly assigned to receive either stereotactic body radiation therapy (SBRT) alone or two cycles of the investigational drug 177Lu-PNT2002 followed by SBRT.

Results showed clear benefits for the combination:

• Progression-free survival: 18 months vs. 7 months with SBRT alone
• Time to hormone therapy: 24 months vs. 14 months
• PSA drops ≥50%: 52% vs. 31%

“Metastasis-directed radiation delays progression, but many patients still recur. That tells us there must be disease present that we can’t see even with advanced imaging,” Dr. Kishan said.

Both treatments were well tolerated, with only a few patients experiencing low white blood cell counts.

Because hormone therapy (ADT) can cause fatigue, bone loss, and other side effects, delaying its use is an important goal. “If we can safely keep people off ADT without compromising outcomes, that’s a meaningful quality-of-life win,” Dr. Kishan said.

While the study shows clear benefit, 64% of patients on the combination still progressed. Dr. Kishan noted the need for research on dosing, sequencing, and therapeutic combinations.