Simple SummaryStereotactic body radiotherapy has a consolidated role in the treatment of oligometastases from prostate cancer. Limited clinical data explored its use in non-spinal bone metastases, as well as details regarding its dose and target definition. We analyzed the outcome of 95 patients treated for 150 non-spinal bone metastases from prostate cancer, aiming to evaluate the local control, the pattern of relapse, and toxicity. The target was represented by the macroscopic disease defined by68Ga-PSMA-PET/CT and CT. The results demonstrated a high local control level and only eight cases of relapse within the same bone. This study provided further evidence supporting the use of SBRT in non-spinal bone metastases from prostate cancer.AbstractBackground and purpose: Stereotactic body radiotherapy (SBRT) has a consolidated role in the treatment of bone oligometastases from prostate cancer (PCa). While the evidence for spinal oligometastases SBRT was robust, its role in non-spinal-bone metastases (NSBM) is not standardized. In fact, there was no clear consensus about dose and target definition in this setting. The aim of our study was to evaluate efficacy, toxicity, and the pattern of relapse in SBRT delivered to NSBM from PCa. Materials and methods: From 2016 to 2021, we treated a series of oligo-NSBM from PCa with68Ga-PSMA PET/CT-guided SBRT. The primary endpoint was local progression-free survival (LPFS). The secondary endpoints were toxicity, the pattern of intraosseous relapse, distant progression-free survival (DPFS), polimetastases-free survival (PMFS), and overall survival (OS). Results: a total of 150 NSBM in 95 patients were treated with 30–35 Gy in five fractions. With a median follow-up of 26 months, 1- and 3 years LPFS was 96.3% and 89%, respectively. A biologically effective dose (BED) ≥ 198 Gy was correlated with improved LPFS (p= 0.007). Intraosseous relapse occurred in eight (5.3%) cases. Oligorecurrent disease was associated with a better PMFS compared to de novo oligometastatic disease (p= 0.001) and oligoprogressive patients (p= 0.007). No grade ≥ 3 toxicity occurred. Conclusion: SBRT is a safe and effective tool for NSBM from PCa in the oligometastatic setting. Intraosseous relapse was a relatively rare event. Predictive factors of the improved outcomes were defined.