New Findings from the LUNAR Trial
A landmark phase II study, known as the LUNAR trial, reports that people with recurrent prostate cancer and a limited number of metastases lived significantly longer without disease progression when a radiopharmaceutical drug was given before targeted radiation therapy, compared with high-precision radiation alone. The randomized study evaluated whether adding a PSMA-targeted radiopharmaceutical could extend the benefits of metastasis-directed radiation in patients with oligometastatic disease.
The trial’s results were presented at the American Society for Radiation Oncology (ASTRO) Annual Meeting and involved 92 men with hormone-sensitive oligometastatic prostate cancer and one to five distant lesions visible on PSMA PET/CT imaging. Participants were assigned to either stereotactic body radiation therapy (SBRT) alone or SBRT preceded by two cycles of the investigational radiopharmaceutical 177Lu-PNT2002, a drug designed to deliver targeted radiation to cancer cells throughout the body.
What Is Radiopharmaceutical Therapy?
Radiopharmaceuticals pair a radioactive dose with a targeting molecule that homes in on cancer cells. In prostate cancer, these therapies commonly target PSMA, a protein often present on tumor cells. When combined with imaging that highlights cancer cell locations, radiopharmaceuticals can expose microscopic disease that traditional imaging may miss, potentially improving disease control when used alongside focused radiation like SBRT.
Study Design and Key Outcomes
Patients were randomized to SBRT alone (n=47) or two cycles of 177Lu-PNT2002 followed by SBRT (n=45). Across a median follow-up of about 22 months, the addition of the radiopharmaceutical significantly improved progression-free survival (PFS). The median PFS was 18 months in the combination arm versus 7 months with SBRT alone (P<0.001). Even after adjusting for PSA levels, prior hormonal therapy, and the number of lesions, the radiopharmaceutical addition remained associated with better PFS.
Another important finding was the ability to delay hormone therapy (androgen deprivation therapy, ADT). Patients receiving the radiopharmaceutical before SBRT could postpone ADT by a median of 24 months, compared with 14 months in the SBRT-alone group (P<0.0001). PSA declines of 50% or greater occurred in 52% of patients on the combination regimen versus 31% on SBRT alone (P=0.04).
Patterns of Progression and Local Control
Almost all disease progression events (98%) were due to new metastases rather than regrowth at treated sites. Local control rates from SBRT were excellent in both groups (98% in SBRT only, 100% with the combination). The authors noted that the study’s sensitive PSMA imaging and protocol-driven scans likely detected progression earlier than in older trials, contributing to higher observed progression events.
Safety and Tolerability
Overall, the combination of radiopharmaceutical therapy with SBRT was well tolerated. There was no increase in severe (grade 3) side effects in the radiopharmaceutical group. The only noteworthy toxicities were low white blood cell counts, observed in a small number of patients (two in the SBRT arm and three in the combination arm).
Clinical Implications and Next Steps
These results reinforce the evolving role of definitive radiation therapy for oligometastatic disease and suggest a new strategy to extend its benefits. Delaying ADT is meaningful, given its potential side effects such as fatigue, metabolic changes, bone loss, and cardiovascular risks. As Dr. Amar U. Kishan emphasized, a safe approach to keep patients off hormone therapy without compromising outcomes represents a significant quality-of-life win for many men with recurrent disease.
It is important to note that 177Lu-PNT2002 is still investigational in this setting and is not approved outside of clinical trials. SBRT and PSMA PET/CT imaging, however, are FDA-approved and increasingly accessible. The LUNAR results pave the way for further research into optimal dosing, sequencing, and combination strategies to address residual microscopic disease in recurrent prostate cancer.
Context in Prostate Cancer Care
While previous trials with different radiopharmaceuticals targeting bone did not show a similar benefit, LUNAR provides evidence that a PSMA-targeted agent can meaningfully extend progression-free survival when used with metastasis-directed SBRT in early metastatic disease. The oncology community will be watching forthcoming studies to determine how best to integrate radiopharmaceutical therapy into standard care for oligometastatic prostate cancer.
