Factors affecting 223Ra therapy: clinical experience after 532 cycles from a single institution

Purpose The aim of this study was to identify baseline features that predict outcome in Ra-223 therapy. Methods We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with Ra-223. End points were overall survival (OS), progression-free survival (PFS), bone event-free survival (BeFS), and bone marrow failure (BMF). The following parameters were evaluated prior to the first Ra-223 cycle: serum levels of hemoglobin (Hb), prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) status, pain score, use of chemotherapy, and external beam radiation therapy (EBRT). During/after Ra-223 we evaluated: the total number of radium cycles (Ra-Tot), the PSA doubling time (PSA(DT)), and the use of chemotherapy, EBRT, abiraterone, and enzalutamide. Results A significant reduction of ALP (p < 0.001) and pain score (p = 0.041) occurred throughout the (223) Ra cycles. The risk of progression was associated with declining ECOG status [hazard ratio (HR) = 3.79; p < 0.001] and decrease in PSA(DT) (HR = 8.22; p < 0.001). Ra-Tot, ALP, initial ECOG status, initial pain score, and use of abiraterone were associated with OS (p <= 0.008), PFS (p <= 0.003), and BeFS (p <= 0.020). Ra-Tot, ALP, initial ECOG status, and initial pain score were significantly associated with BMF (p <= 0.001) as well as Hb (p < 0.001) and EBRT (p=0.009). On multivariable analysis, only Ra-Tot and abiraterone remained significantly associated with OS (p < 0.001; p=0.033, respectively), PFS (p < 0.001; p=0.041, respectively), and BeFS (p < 0.001; p=0.019, respectively). Additionally, Ra-Tot (p=0.027) and EBRT (p=0.013) remained significantly associated with BMF. Conclusion Concomitant use of abiraterone and Ra-223 seems to have a beneficial effect, while the EBRT may increase the risk of BMF.