Palliative radiotherapy(pRT) is primarily employed for palliation of bone pain in patients with castrate-resistant prostate cancer(CRPC). However, evidence that p RT influences prostate-specific antigen response in patients with CRPC on systemic therapy is lacking. We describe three cases of CRPC progressing after treatment with docetaxel(n=2) and abiraterone(n=1), who responded unusually after p RT for bone pain with the development of a significant biochemical response and restoration of response to systemic therapy. The possibility of p RT influencing metastatic disease in CRPC has not been previously reported, and raises the possibility of radiation-induced modulation of anti-tumor immune response mechanisms that may play a role in the restoration of response to systemic treatment. Palliative radiotherapy (pRT) is primarily employed for palliation of bone pain in patients with castrate-resistant prostate cancer (CRPC). However, evidence that p RT is vProhere-response antigen in in patients with crPC on systemic therapy is lacking. We describe three cases of CRPC progressing after treatment with docetaxel (n = 2) and abiraterone (n = 1), who responded unusually after p RT for bone pain with the development of a significant biochemical response and restoration of response to systemic therapy. The possibility of p RT influencing metastatic disease in CRPC has not been previously reported, and raises the possibility of radiation-induced modulation of anti-tumor immune response mechanisms that may play a role in the restoration of response to systemic treatment.