Background: prostate cancer is the second most frequent cancer worldwide, with a very high rate of progression despite treatment. The most aggressive form of the disease is known as castration-resistant prostate cancer, which carries a poor prognosis. Castration resistant prostate cancer (PC) patients are a niche of patients affected by progressive prostate cancer despite androgen deprivation therapy (ADT) and a serum testosterone value < 50 mg/dl. Androgen receptor targeted therapy (ARTT) as it has been shown for Enzalutamide and Abiraterone in phase III clinical trials, has high efficacy in patients with metastatic castration resistant prostate cancer (mCRPC), leading to improved overall survival. Methods: we reviewed available literature regarding the combination of enzalutamide antihormonal drug and ablative radiation therapy for the treatment of metastatic castration-resistant prostate cancer. This combination treatment is safe and effective, with few adverse events. This dual treatment may enhance the effects of second-line hormonal therapy, as radiotherapy renders cancer cells more prone to immune-mediated cytotoxicity. Moreover, radiotherapy exerts its effect both on directly irradiated cells and on other distant tissues, with an abscopal effect, already demonstrated in other solid tumors. Results: in the available literature, the combination of radiation therapy and enzalutamide has prolonged both overall survival and progression-free survival, with a positive impact also on locoregional recurrence and distant metastases.
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