Predictors of poor response to first-generation anti-androgens as criteria for alternate treatments for patients with non-metastatic castration-resistant prostate cancer

Purpose There are no criteria for administering first- or second-generation anti-androgens (FGA and SGA, respectively) to patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This study aimed to assess the efficacy of alternative FGA therapy in nmCRPC patients and the prognosis of these patients and to identify factors for predicting patients potentially responsive to FGA. Methods Data from 63 men with nmCRPC who underwent alternative FGA therapy (bicalutamide, flutamide, or chlormadinone acetate) as first-line therapy after failure of primary androgen-deprivation therapy (PADT) between 2004 and 2017 at Hiroshima University Hospital and affiliated hospitals were retrospectively investigated. The associations of clinicopathological parameters with overall survival (OS) and prostate-specific antigen (PSA) progression-free survival (PFS) of alternative FGA-treated patients were analyzed. Results Time to CRPC [ p = 0.007, hazard ratio (HR) = 4.77], regional lymph node involvement at the diagnosis of CRPC ( p = 0.022, HR = 2.42), and PSA-PFS of alternative FGA therapy ≤ 6 months ( p = 0.020, HR = 2.39) were identified as prognostic factors using a multivariate analysis. Additionally, Cox proportional hazard models revealed that PSA nadir value > 1 ng/mL during PADT ( p = 0.034, HR = 2.40) and time from starting PADT to PSA nadir ≤ 1 year ( p = 0.047, HR = 1.85) were predictive factors for worse PSA-PFS in alternative FGA therapy. Conclusions Shorter time to CRPC, regional lymph node involvement, PSA nadir during PADT > 1 ng/mL, and time from starting PADT to PSA nadir ≤ 1 year might suggest the potential benefit of immediate commencement of SGA, compared to FGA administration after nmCRPC diagnosis.