Clinical Outcome Patterns of Use of Radium-223 in Patients with Metastatic Castration-Resistant Prostate Cancer

Abstract

Introduction: Radium-223 dichloride (radium-223) is a bone-targeting radioisotope therapy that aids in the survival of patients with metastatic castration-resistant prostate cancer (mCRPC) to bones. This study aimed to describe the clinical characteristics and outcomes of patients with mCRPC treated with radium-223 in a real-world setting. Methods: This was a retrospective study of patients with mCRPC treated with radium-223 between 2016 and 2020 at the London Health Sciences Centre in London, Canada. The baseline characteristics between the patients receiving 1-3 and 4-6 treatment cycles were compared using a two-sample t-test and Chi-square test. ANOVA was used to determine if there was a difference in each diagnostic variable per treatment cycle. Kaplan-Meier curves were generated to estimate progression-free survival (PFS) and overall survival in the patients treated with different numbers of cycles. Results: Fifty eligible patients were identified. The median age was 71 years (IQR: 66-76). Most patients (62%) received radium-223 beyond the third-line treatment. The mean number of radium-223 treatments was four. While 60% of the patients received 4-6 injections, 40% received 1-3 injections. Fifty-eight percent (58%) of the patients demonstrated a clinical benefit, with the remainder expressing either disease progression (28%) or stable disease (10%). The patients treated with 4-6 cycles had a delay to disease progression compared to those given 1-3 cycles of radium-223 (F_5,35 = 10.52, p < 0.001). A higher alkaline phosphatase level prior to treatment was associated with a longer PFS (z₃₃ = 2.362, p = 0.018). Treatment-related hospitalization for skeletal-related events was noted in 8% of the patients, and 14% required treatment discontinuation due to hematologic toxicity. Conclusions: This study confirms the safety of radium-223 in patients with mCRPC in a real-world setting. The radium-223 treatment was associated with a clinical benefit in the majority of the patients, particularly in those with higher pre-treatment serum alkaline phosphatase levels. Further studies to identify the predictive biomarkers are warranted to better guide the contemporary use of radium-223.

Keywords: bone metastasis; castration-resistant prostate cancer; clinical outcomes; radium-223.

Figure 1

Correlations between patient variables before and after first radium-223 treatment cycles, where significant correlations are indicated by trendline (p < 0.05).

Figure 2

ANOVA analysis to determine statistical significance in time to progression between patients treated with different numbers of cycles of radium-223. Boxplot includes the distribution of time to progression per number of treatment cycles. Outliers are indicated with a dot, but they were not removed per intent to treat. Different letters indicate statistically significant differences (p < 0.05).

Figure 3

Kaplan–Meier estimates of progression-free survival of patients who underwent 1–3 cycles or 4–6 cycles.

Figure 4

Kaplan–Meier estimates of progression-free survival of patients who underwent 1–4 cycles or 5–6 cycles.

Figure 5

Kaplan–Meier estimates of overall survival of patients receiving 1–3 cycles or 4–6 cycles.

Figure 6

Kaplan–Meier estimates of overall survival of patients receiving 1–4 cycles or 5–6 cycles.