What the LUNAR trial tested
SAN FRANCISCO, September 28, 2025 — A new phase II clinical trial, called LUNAR, shows that adding a radiopharmaceutical drug before high-precision radiation therapy can help people with a limited number of metastatic lesions from recurrent prostate cancer live longer without disease progression. In this randomized study, patients received either standard metastasis-directed radiation therapy (SBRT) alone or SBRT preceded by two cycles of a PSMA-targeted radiopharmaceutical, 177Lu-PNT2002.
The trial enrolled 92 men with hormone-sensitive oligometastatic prostate cancer—defined as one to five distant metastases identified on PSMA PET/CT—and randomly assigned them to SBRT alone (n=47) or the combination treatment (n=45). Participants were followed for a median of about 22 months to monitor PSA levels and scan-based evidence of progression.
Why this matters for early-stage oligometastatic disease
Metastasis-directed SBRT is increasingly used to control visible disease and delay systemic therapies. However, many patients harbor microscopic cancer that current imaging can’t detect. The LUNAR trial explores whether radiopharmaceutical therapy can reach these undetectable cancer cells, potentially enhancing the effectiveness of SBRT and delaying the need for androgen deprivation therapy (ADT), a cornerstone of treatment that can significantly affect quality of life.
Key results at a glance
Adding the PSMA-targeted radiopharmaceutical before SBRT substantially improved progression-free survival. Median progression-free survival was 18 months in the combination arm versus 7 months with SBRT alone (p<0.001). After adjusting for PSA, prior hormonal therapy, and the number of lesions, the benefit persisted, underscoring a real effect from radiopharmaceutical therapy.
Hormone therapy could be delayed by a median of 24 months with the combination approach, compared with 14 months for SBRT alone (p<0.0001). PSA declines of at least 50% were achieved in 52% of patients receiving the radiopharmaceutical plus SBRT, versus 31% in the SBRT-only group (p=0.04).
Local control from SBRT was excellent in both arms, with 98% in the SBRT group and 100% in the combination group. Notably, almost all progression events (98%) were new metastases rather than regrowth at treated sites, reflecting the ongoing challenge of microscopic disease that escapes detection even with sensitive imaging.
Safety and tolerability
Overall, both treatment strategies were well tolerated. There was no increase in severe (grade 3) adverse events with the addition of the radiopharmaceutical. The only noted severe toxicity comprised modest reductions in white blood cell counts (two patients in the SBRT arm and three in the combination arm).
Implications for practice and future research
Dr. Amar U. Kishan, the trial’s principal investigator from the University of California, Los Angeles, emphasized that the results support a growing role for definitive radiation therapy in oligometastatic disease. “Hormone therapy remains a cornerstone of care, but if we can safely keep people off ADT without compromising outcomes, that’s a meaningful quality-of-life win.”
While 177Lu-PNT2002 is investigational in this setting, the findings suggest a potential new standard of care for carefully selected patients when paired with SBRT. The trial also highlights that although radiopharmaceutical therapy can extend disease control, residual microscopic disease remains a critical challenge, underscoring the need for continued optimization of dosing, sequencing, and combination strategies.
What comes next
LUNAR is the first randomized study to show a survival and disease-control benefit from adding radiopharmaceutical therapy to metastasis-directed SBRT for recurrent prostate cancer. Other radiopharmaceutical approaches targeting bone versus tumor tissue have produced mixed results, reminding clinicians that patient selection and treatment sequencing are crucial. As SBRT and PSMA PET/CT become more accessible in the United States, ongoing trials will help determine the broader applicability and optimal use of radiopharmaceuticals like 177Lu-PNT2002 in earlier disease settings.
Limitations
The study is phase II and relatively small, and 177Lu-PNT2002 remains investigational outside of trials. Long-term outcomes and real-world feasibility will require further research.
