New approach combines Lu-177 PNT2002 with SBRT
In a pioneering study presented at the American Society for Radiation Oncology (ASTRO) meeting, researchers explored whether adding lutetium-177 (Lu-177) PNT2002 to stereotactic body radiation therapy (SBRT) could improve outcomes for men with oligometastatic, or limited, prostate cancer. The strategy targets occult micrometastases that often drive progression after initial therapy.
PSMA-based radioligand therapy, which couples Lu-177 with ligands that bind to the prostate-specific membrane antigen (PSMA) on cancer cells, represents a promising avenue for treating advanced cancers. The LUNAR trial tested two cycles of Lu-177 PNT2002 before SBRT versus SBRT alone, aiming to suppress hidden metastases and extend disease control while preserving tolerability.
Trial design and key findings
The study enrolled 92 patients with oligometastatic prostate cancer, randomly assigning them to SBRT alone (n = 47) or two cycles of Lu-177 PNT2002 followed by SBRT (n = 45). Patients were followed for a median of 22 months. The results demonstrated a substantial improvement in progression-free survival (PFS) for the combination arm: 18 months versus 7 months with SBRT alone (P<0.001). Even after adjusting for PSA levels, prior hormonal therapy, and the number of metastatic lesions, Lu-177 PNT2002 remained independently associated with longer PFS.
Remarkably, delaying systemic therapy was also observed: patients receiving Lu-177 PNT2002 before SBRT could postpone hormone therapy by a median of 24 months compared with 14 months for SBRT alone (P<0.0001).
PSA declines of 50% or greater occurred in 52% of patients in the combination arm versus 31% in the SBRT-only group (P = 0.04), signaling deeper biochemical responses in the Lu-177–augmented group. Importantly, treatment was well tolerated, with no increase in high-grade toxicities observed in the combination arm.
Safety, imaging, and interpretation
Researchers noted that nearly all disease progression events (98%) represented new metastatic sites rather than regrowth at treated locations. The higher rate of progression events likely reflects the sensitivity of modern PSMA-PET/CT imaging used in the trial, which detects smaller metastatic deposits that could predate clinical progression.
Even with the encouraging PFS gains, the investigators emphasized that progression remained a reality for a substantial portion of patients. Approximately 64% of participants in the study experienced some progression during follow-up, underscoring the need for further optimization of dosing, cycle number, or sequencing to maximize benefit.
Implications for patients and future directions
As an early look into combining PSMA-based radioligand therapy with metastasis-directed SBRT, the LUNAR trial supports the hypothesis that Lu-177 PNT2002 can enhance control of micrometastatic disease and delay systemic treatment without adding toxicity. These findings may influence the management of oligorecurrent prostate cancer, offering a strategy to extend disease control and postpone hormone therapy for selected patients.
Experts caution that results are exploratory and that optimization of dosing regimens, cycle timing, and patient selection will be essential steps before widespread adoption. Ongoing work will aim to refine the balance between maximizing anti-tumor activity and minimizing side effects, while investigating which patients reap the most durable benefit from this targeted radiopharmaceutical approach.
Bottom line
The combination of Lu-177 PNT2002 with SBRT shows promise in delaying progression for men with oligometastatic prostate cancer, with meaningful improvements in PFS and hormone therapy–free intervals and without added toxicity. As research advances, this strategy could become a valuable option in the prostate cancer treatment landscape, particularly for patients with limited metastatic disease who seek longer periods of disease control.
