Reversibility of castration resistance status after Radium-223 dichloride treatment: clinical evidence and review of the literature

In the history of prostate cancer, some of the patients progressed to castration-resistant prostate cancer (CRPC) stage and, although new drugs and treatment protocols have been introduced, CRPC presents poor prognosis. This review is focused on biological mechanisms, underlying CRPC described in scientific literature in order to explain the reversion of resistance to castration. We present the case of a 73-year-old man, affected by bone metastatic CRPC, early treated with Radium-223 with a complete response. After 15 months from Radium-223 treatment, prostate-specific antigen increased with radiological progression. Androgen deprivation therapy was again performed and was effective, despite previous CRPC condition and no known mechanisms that may explain the reversion of this condition. Therefore, to our knowledge, he is the unique described case of the reversion of resistance to castration. Nevertheless, promising aspects may be lack of intrametastatic production of androgen or the suppression of bypass androgen receptor signaling pathways. Furthermore, the cytotoxic action of Radium-223 on cancer stem cell (CSC), due to surrounding clones with high-bone turnover, or the immune response that underlying the abscopal effect, may also modulate the reversion of CRPC after Radium-223. If confirmed by multicenter trials, the reversion of CRPC may impact on the management of prostate cancer.