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

The aim of this study was to identify baseline features that predict outcome in ²²³Ra therapy.

We retrospectively reviewed 110 patients with metastatic castration-resistant prostate cancer treated with ²²³Ra. 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 ²²³Ra 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 ²²³Ra 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.

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.

Concomitant use of abiraterone and ²²³Ra seems to have a beneficial effect, while the EBRT may increase the risk of BMF.