A clinical trial led by researchers at UCLA has revealed that combining PSMA-targeted radioligand therapy with stereotactic body radiotherapy (SBRT) significantly extends the time men with recurrent prostate cancer live without disease progression. The Phase 2 LUNAR trial demonstrated that this novel dual approach more than doubles progression-free survival compared to SBRT alone, offering renewed hope for improving outcomes and quality of life in this challenging setting.

The LUNAR trial enrolled 92 men with oligorecurrent prostate cancer, a form where cancer has returned in a limited number of sites. Participants were randomly assigned to receive either SBRT alone or two injections of the radioligand drug 177Lu-PNT2002 spaced six to eight weeks apart, followed by SBRT targeting all visible tumors. This approach aimed to eradicate both the tumors identifiable by imaging and microscopic disease that conventional techniques often miss.

Patients treated with the combination regimen experienced a median progression-free survival of 17.6 months, more than double the 7.4 months observed in those receiving SBRT alone. Moreover, the combined therapy delayed the need for hormone therapy by nearly a full year, with a median of 24.3 months versus 14.1 months in the radiation-only group. This delay is particularly meaningful, as hormone therapy is associated with significant side effects impacting quality of life, including fatigue and bone density loss.

The combined treatment also reduced the risk of cancer relapse, hormone therapy initiation, or death by 63%, while not causing significantly greater side effects. Some patients experienced moderate reductions in white blood cell counts, but no major toxicities were reported.

The trial included detailed biological analyses that linked better outcomes to patients with higher immune system activity, as shown by changes in T-cell receptor signaling. Genetic differences in immune and DNA repair genes were also identified as potential predictors of treatment success. These insights could pave the way for more personalized therapies tailored to each patient’s unique cancer biology.

Experts highlight that this “theranostic” strategy—combining diagnosis and therapy in one—exemplifies the future of prostate cancer care. It offers the possibility of delaying or even avoiding the need for hormone therapy, thereby preserving patients’ strength and bone health longer.

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