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A progressively rising level of serum prostate specific antigen (PSA) after radical prostatectomy (RP) invariably indicates the recurrence of prostate cancer. The optimal management of patients with post-RP PSA relapse has remained uncertain due to a wide variability in the natural course of post-RP PSA relapse and the inability to separate a recurrent disease confined to the prostate bed from that with occult distant metastasis. Management uncertainty is further compounded by the lack of phase III clinical studies demonstrating which therapeutic approach, if any, would prolong life with no significant morbidity. Radiotherapy has been the main therapeutic modality with a curative potential for patients with post-RP PSA relapse. This review article depicts issues and challenges in the management of patients with post-RP PSA relapse, presents the literature data for the efficacy of salvage radiotherapy, either alone or in combination of androgen ablation therapy, and discusses future directions that can optimize treatment strategies.

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