Metastasis directed radiotherapy (MDRT)

This will be a pragmatic, phase II, registry-based cohort-multiple randomized controlled trial (cmRCT) embedded within an ongoing prospective cancer radiotherapy registry. Eligible patients are those with hormone-sensitive metastatic prostate cancer who have responded to systemic therapy, defined by the absence of PSA progression, and who are eligible for MDRT. All eligible subjects will be enrolled into the registry and followed longitudinally for oncologic and toxicity outcomes. From this registry, patients will be randomly selected (1:1) to be offered the experimental arm, which consists of MDRT delivered to metastatic sites identified on imaging in patients who have already initiated systemic therapy (Figure 1). Those not selected will continue to receive standard of care systemic therapy +/- standard of care radiotherapy if clinically indicated. Nor patients or physicians will be blinded. Following the initial course of MDRT, prostate-specific antigen (PSA) will be measured, with a minimum assessment at 3 months. This PSA value will be used to determine whether the PSA level has decreased below 0.2 ng/mL. If the PSA remains ≥ 0.2 ng/mL, repeat PSMA-PET will be performed, and a second course of MDRT will be delivered to consolidate residual metastatic lesions. In this phase II real-world randomized trial, we will determine if AnChoRing (Addition of MDRT for consolidation of response) sites of PSMA PET visible disease when responding to systemic therapy improves the proportion of patients achieving a PSA \< 0.2 ng/mL and extends failure-free survival compared to the standard of care.

The purpose of this study is to find out if giving radiation therapy (RT) to areas of metastatic prostate cancer at the time a participant is diagnosed will help control disease better than the usual treatment. This treatment is called metastasis-directed radiotherapy (MDRT). The usual treatment for prostate cancer that has spread to other parts of the body is to give lifelong treatment with hormone therapy (also known as androgen deprivation therapy or ADT). Participants may also be given prostate RT even if the disease is metastatic. Participants will receive hormone therapy (the standard treatment for prostate cancer) for 12 months. The hormone therapy agents may be taken by mouth or given as an injection. Participants will also have prostate RT. Up to 50 participants will have surgery to remove the prostate instead of having prostate RT. A portion of the participants will be randomized to receive MDRT to areas where the cancer has spread. For participants who have surgery to remove their prostate, they will be asked to allow tissue samples collected during the surgery to be sent to an outside lab for research tests and extra blood samples drawn for research tests before starting the study, and at the time the cancer becomes worse if applicable. Participation in the study will last approximately 12 months, and will be followed by their doctor for up to five years per standard of care. The main goal is to compare the efficacy of the standard of care (standard systemic therapy + definitive prostate-directed local therapy) versus the standard of care with metastasis-directed radiotherapy (MDRT) for consolidation of metastatic disease.