Shuji Sugimoto

Prospective study on the relationship between clinical efficacy of secondary hormone therapy with flutamide and neuroendocrine differentiation in patients with relapsed prostate cancer after first line hormone therapy

Abstract Objective. The aim of this study was to prospectively verify the relationship between the clinical efficacies of secondary hormone therapy for castration-resistant prostate cancer (CRPC) following first line hormone therapy and neuroendocrine differentiation (NED). Material and methods. Forty-six consecutive patients with CRPC following first line hormone therapy who were treated with flutamide as secondary hormone therapy were prospectively assessed with a median follow-up of 21 months. Serum chromogranin A (CgA), as a marker of NED, was measured using an immunoradiometric assay. Results. Of the 46 patients, 22 (48%) responded to the secondary hormone therapy as a 50% or more reduction from baseline prostate-specific antigen (PSA) with a median response duration of 9.2 months. The PSA response group was correlated with significantly favorable cancer-specific survival (CSS) (92% vs 59% at 5 years, p = 0.0146) compared with the non-response group. Above-normal CgA levels at study entry were detected in 15 patients (33%), but no association with CSS was identified. Data on CgA kinetics were available in 35 patients. The CgA levels before and at 3 months during the treatment were similar. However, eight patients (23%) with an increase in CgA level of a quarter or more from baseline had a tendency for worse CSS (63% vs 84% at 5 years, p = 0.0507) compared with the remaining patients. Conclusion. Within limitations, in this study secondary hormone therapy with flutamide was effective for CRPC following first line hormone therapy. The above-normal CgA level in the first hormone resistance phase is mostly unrelated to prognosis. However, some patients with a remarkable increase in CgA in a short duration may have an unfavorable prognosis caused by NED as well.