Radium-223 is an approved treatment for symptomatic bone metastatic castration-resistant prostate cancer (mCRPC). While previous trials demonstrated improvements in pain and HR-QoL, data on HR-QoL, psychological distress, and fatigue in real-world mCRPC patients treated with radium-223 are limited. This study aimed to evaluate these outcomes in a daily practice setting, hypothesizing that patients completing the full course of radium-223 therapy would have different HR-QoL trajectories compared to those who discontinued treatment. The study also sought to identify baseline variables associated with HR-QoL deterioration.

Prior research, primarily from phase 3 trials like ALSYMPCA, showed radium-223's efficacy in improving pain and HR-QoL in mCRPC patients. However, these trials often used HR-QoL instruments not specifically designed for mCRPC and involved highly selected populations, potentially leading to discrepancies with real-world outcomes. There was a lack of studies focusing on psychological distress and fatigue in daily practice settings, despite the potential impact of these factors on overall patient well-being.

This prospective, observational, multicenter cohort study enrolled 124 patients, with 122 included in the final analysis. Primary endpoints were cancer-specific and bone metastases-related HR-QoL, assessed using the EORTC QLQ-C30 and BM-22 questionnaires. Secondary endpoints included psychological distress (HADS) and fatigue (CIS-Fatigue). Outcomes were analyzed for the total cohort and subgroups based on the number of radium-223 injections (1-3 vs. 4-5 vs. 6). A trajectory analysis explored HR-QoL patterns over time, examining baseline variables (age, marital status, ECOG performance status, opioid use, prior therapies, hemoglobin, alkaline phosphatase, and PSA levels) as potential predictors of HR-QoL trajectories. Statistical analyses included Chi-square, Fisher’s Exact, Mann-Whitney, Kruskal-Wallis, paired t-tests, Kaplan-Meier curves, log-rank tests, and multinomial logistic regression.

A total of 122 patients were analyzed. Baseline HR-QoL, pain, psychological distress, and fatigue were worse in patients who did not complete radium-223 therapy. Patients completing therapy showed stabilization of HR-QoL, with only minor changes in global health status and physical and role functioning. In contrast, patients discontinuing treatment experienced clinically meaningful deterioration in all EORTC QLQ-C30 functioning scales. Trajectory analysis revealed that HR-QoL deterioration was more likely in patients with baseline opioid use, low hemoglobin, and high alkaline phosphatase levels. Physical and role functioning were the most affected HR-QoL domains. Patients discontinuing radium-223 experienced increased psychological distress and fatigue over time.

This study highlights the importance of patient selection for radium-223 therapy and close monitoring of HR-QoL during treatment. The observed deterioration in HR-QoL, psychological distress, and fatigue among patients who discontinued therapy emphasizes the need for careful consideration of treatment discontinuation and proactive management of associated symptoms. The identification of baseline opioid use, low hemoglobin, and high alkaline phosphatase levels as predictors of HR-QoL deterioration underscores the need for tailored interventions in these patients. The study results support incorporating regular HR-QoL assessments into clinical practice to optimize treatment decisions and improve patient outcomes.

Patients completing radium-223 therapy experienced stabilization of HR-QoL, psychological distress, and fatigue. Discontinuation of therapy was associated with worse baseline scores and significant deterioration over time. Baseline opioid use, low hemoglobin, and high alkaline phosphatase levels predicted HR-QoL decline, indicating a need for close monitoring and tailored interventions in these patients. Future research should focus on validating these findings in larger cohorts and exploring interventions to mitigate HR-QoL deterioration.

The observational nature of the study limits causal inferences. The chosen time points for HR-QoL assessment might have missed important information. While the multicenter design and high compliance rates are strengths, the relatively small sample size in some trajectory analysis subgroups limits generalizability.