There is no effective standard therapy for the treatment of hormone refractory prostate cancer (HRPC), andtreatments vary among different medical institutions with efforts to improve results. The present retrospectiveinvestigation was performed to assess the outcomes of second line, third line, and fourth line therapies. A total of142 patients with HRPC were treated at Nagoya City University Hospital and its affiliate hospitals during the 10years between October 1996 and August 2006. Patient background and treatments given after hormone refractoryphase were determined, with especial attention to 50% or greater decrease rates of serum PSA levels and othervariables with three common regimens based on: estramustine phosphate (EMP); diethylstilbestrol diphosphate(DES); and dexamethasone (DEX). With second line therapy for HRPC, the response rate was highest withEMP, whereas best outcomes were apparent with DES as a third line or fourth line therapy. However, overallsurvival for all cases and particularly with those having a poorly differentiated lesion, was best with EMP in anytime period. Although there is no generally established optimal treatment for HRPC, our analysis supports theefficacy of EMP based on second line therapy response rates and optimal prognosis with longer term use.