Objectives: To identify patients who benefit from the salvage hormonal therapy in men with advanced prostate cancer who relapsed after primary hormonal therapy. Patients and Methods: The study included 68 patients treated with primary combined androgen blockade followed by second-line antiandrogen therapy at prostate-specific antigen (PSA) relapse. The cause-specific survival after second-line therapy was compared according to various clinical factors. Results: Of the several variables isolated as prognostic factors, the duration of response to first-line therapy remained as an independent prognostic factor by multivariate analysis. The comparative survival curves constructed according to the duration of response in first-line therapy and the responsiveness to second-line therapy clearly discriminate the patients' survival. The nadir PSA level in first-line therapy was well substituted for the responsiveness to second-line therapy, thereby enabling to predict the clinical outcome using the readily available variables before second-line therapy. Namely, the patients who failed to attain the duration of response ≥12 months and the nadir PSA <0.2 ng/ml in first-line therapy are unlikely to benefit from second-line therapy. Conclusions: These results may imply an inherent unresponsiveness to salvage hormonal therapy in patients who showed insufficient response to primary hormonal therapy and therefore an early introduction of chemotherapy might be an option for such patients.

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