RAdium-223 and SABR Versus SABR for Oligometastatic Prostate Cancers

The metastatic capacity of prostate cancer (PCa) behaves along a spectrum of disease that contains an oligometastatic state where metastases are limited in number and location. The importance of local consolidation of all tumor deposits in oligometastatic disease to forestall further metastatic dissemination is now backed by small randomized studies. Our previous Baltimore ORIOLE randomized trial of stereotactic ablative radiation (SABR) alone, highly focused, high-dose radiation, versus observation in oligometastatic PCa final data demonstrate a progression-free survival (PFS) benefit of SABR alone. The patterns of failure from our ORIOLE trial in combination with prior data suggest one dominant mode of failure is from microscopic disease particularly those with bone-tropic biology. These are important early clinical data suggesting the existence of an oligometastatic state and the importance of local therapies in the management of these patients. Radiopharmaceutical therapy (RPT) approaches have not been applied in the oligometastatic space and thus the opportunity to target micrometastatic disease in conjunction with local consolidation of macroscopic disease with SABR has the potential to provide a curative paradigm for patients with oligometastatic PCa. We introduce the successor trial to ORIOLE called RAVENS that is a phase II randomized trial of SABR +/- the bone metastasis seeking RPT Xofigo in men with oligometastatic PCa. We hypothesize macroscopic prostate tumors support the growth of and help nurture future distant metastases and this process can be impacted most by total, macro- and microscopic, tumor consolidation. In addition, we hypothesize that circulating biomarkers can identify men with oligometastasis that benefit the most from SABR and RPT.