Anticancer Effect of Second-line Treatment for Castration-Resistant Prostate Cancer Following First-line Treatment with Androgen Receptor Pathway Inhibitors

INTRODUCTION: Studies on the effect of androgen receptor pathway inhibitors (ARPI), docetaxel (DTX), and radium-223 (Ra-223) after first-line treatment with ARPI in patients with castration-resistant prostate cancer (CRPC) are scarce. This study compared the efficacy of treatment after ARPI for CRPC. METHODS: Patients with CRPC who received ARPI as first-line treatment and different second-line treatments were retrospectively reviewed. Clinicopathological backgrounds and treatment outcomes, including maximum prostate-specific antigen (PSA) decrease, progression-free survival (PFS), and overall survival (OS), were compared between second-line treatments. RESULTS: In total, 88 patients were enrolled. Forty-one (46.6%), 37 (42.0%), and 10 (11.4%) patients were treated with ARPI, DTX, and Ra-223, respectively. Patients whose PSA levels were not adequately reduced by first-line treatment with ARPI were eventually enrolled in the DTX treatment (P = 0.030). PSA decrease was not significantly different when comparing treatments. PFS in the DTX group was significantly better than in the other two groups (P = 0.023). In multivariate analysis, DTX was an independent prognostic factor for better PFS compared to ARPI (hazard ratio, 95% confidence interval; 0.44, 0.25-0.79, P = 0.006). Subgroup analysis showed a favorable impact of DTX on PFS in patients with Gleason score >8 (interaction P = 0.027) and a PSA decline >50% (interaction P = 0.019) during first-line treatment with ARPI. However, no significant difference in OS was observed between groups of different second-line treatments. CONCLUSIONS: This study suggests that in patients with CRPC, second-line treatment with DTX following progression in patients who received ARPI as first-line treatment is more beneficial compared with second-line treatment with ARPI or Ra-233.