In prostate cancer, disease progression after primary treatment and subsequent androgen deprivation therapy is common. Intensification of systemic treatment is the standard of care. Recently, 68Ga prostate-specific membrane antigen positron emission tomography (PSMA-PET) imaging was introduced to identify oligometastatic prostate cancer patients. In this retrospective, exploratory study, we report on the efficacy of PSMA-PET-guided local ablative radiotherapy (aRT) in 15 oligometastatic castration-resistant prostate cancer (CRPC) patients, selected from our prospective institutional database and treated between 2013 and 2016. After multidisciplinary discussion, aRT was delivered with two different schedules. Androgen deprivation therapy remained unchanged. Prostate-specific antigen (PSA) response and time to PSA progression were analysed. For comparison, individual time to PSA progression without aRT was estimated by individual PSA doubling time (PSADT). PSA response was observed in 11 patients (73%). Mean time to PSA progression or last follow-up was 17.9mo, as opposed to 2.9mo estimated from the PSADT without aRT (p<0.001). A relevant subset of CRPC patients had a PSA response with aRT to PET-positive lead metastases. A prospective trial is in preparation. PATIENT SUMMARY: In selected patients with prostate-specific antigen (PSA) increase during androgen deprivation, metastases were detected with prostate-specific membrane antigen positron emission tomography imaging. Fifteen patients with three or fewer metastases were treated with high-dose radiotherapy. Subsequently, PSA values dropped in 11 patients and in six patients no PSA progression was detected for >12mo.