RIPCORD Phase 1 Trial: Interim PSMA PET–Guided Adaptive Radiotherapy in Metastatic Castration-Sensitive Prostate Cancer

RIPCORD is a UT Southwestern phase 1 trial testing a simple but important idea: can PSMA PET be used during treatment to decide how much metastasis-directed radiotherapy a patient actually needs? It focuses on men with poly-metastatic castration-sensitive prostate cancer and uses interim 68Ga-PSMA-11 PET to adapt stereotactic ablative radiotherapy (SABR) rather than giving every lesion the same full treatment upfront.

Patients first receive standard systemic therapy, including ADT and, when appropriate, an androgen receptor pathway inhibitor. The study then plans SABR to all visible PSMA-avid metastases, typically in five fractions, but it delivers the treatment in weekly pulses. After three pulses, the team repeats PSMA PET at about six months from ADT start to see which lesions have fully responded and which still show active disease.

The key feature is adaptation. Lesions with complete metabolic response may not need further radiation, while lesions with residual PSMA uptake can receive two additional pulses. In practical terms, the trial is trying to reduce overtreatment in responding lesions and concentrate radiation on the disease that appears biologically persistent.

Why this matters is straightforward. PSMA PET is more sensitive than standard imaging for prostate cancer metastases, and PSMA-based response measures have already shown prognostic value in other advanced prostate cancer settings. RIPCORD takes that evidence one step further by asking whether imaging response can directly guide treatment intensity, not just predict outcome.

The trial is also notable because it moves beyond the usual oligometastatic setting and into poly-metastatic disease, where treatment decisions are more complex. If the approach works, it could become a more efficient way to combine systemic therapy and local treatment, with less unnecessary radiation and better targeting of resistant lesions.

Clinical trial.