Response With Interim PSMA PET in Metastatic Castration-sensitive Prostate Cancer for Optimization of Adaptive Metastasis-directed Radiotherapy Delivery

This study will enroll patients with poly-metastatic hormone-sensitive prostate cancer, as identified by baseline PSMA PET imaging. All participants will undergo standard of care systemic therapy, including ADT and androgen receptor signaling inhibitors intensification as clinically indicated, for up to three months before protocol radiotherapy. The treating radiation oncologist will pre-plan SABR to a total of 35-40 Gy in 5 fractions. The study will consist of initially delivering three qWeekly SABR "pulses" to all identified metastatic sites. The initial pulse should start within 60 (+/-30 days) of initiation of ADT. Following the third pulse, interim PSMA PET imaging will be repeated at 6 months from initiation of ADT (-30 days allowed) to evaluate the response on a per lesion basis (See Section 6.1.2.1). In the absence of a complete response (CR) for a given lesion, two additional qWeekly pulses may be delivered to these sites within 60 days from interim PSMA PET. PSMA avid lesions identified at baseline will be monitored on interim and follow up scan, and new PSMA avid lesions will require confirmation through conventional imaging. If patients exhibit progression on PSA or conventional imaging, they will exit the trial and undergo systemic therapy intensification. More detailed specifications on systemic therapy and SABR and their parameters are provided in the protocol.