Utilization of Radium-223 in Metastatic Prostate Cancer Patients and Novel Prognostic Indicators In Radium-223 Patients

Abstract

Radium-223 (R-223) is a radiopharmaceutical treatment approved for patients with metastatic castration resistant prostate cancer with symptomatic bony metastases. We sought to examine the utilization and patterns of care of this treatment at a large NCCN and NCI comprehensive cancer center. We also looked to examine predictors of survival after radium treatment in our dataset. A professionally curated, prospectively gathered institutional database was queried for prostate cancer patients treated with R-223 from 2013 to 2019. We analyzed this cohort for patterns of care including the time from initiation of systemic treatment to the initiation of R-223, the number and type of treatment courses prior to R-223 and the number of treatments following R-223. Kaplan Meier analyses and Cox proportional hazards modeling was used to examine an endpoint of overall survival (OS) from the time of administration of R-223 in sub-groups including those who received R-223 early in their treatment course, as well as those with high and low hemoglobin levels prior to R-223 administration. We identified 74 unique patients who were treated with R-223 over the study period at a single institution. The median OS for all patients following R-223 administration was 537 days. On average Radium-223 was initiated over four years following the initiation of the first systemic therapy (1508 days, range 183-6820 days). On average R-223 was the 5th systemic therapy course these patients received (range 2-11). We found that patients who received R-223 later in their treatment course, defined as the 4th systemic therapy or later, had an increased risk of death compared to those who received R-223 as an earlier line (HR 4.59 95% CI 1.36-15.42). Patients received an average of 0.64 systemic treatments following R-223 (range 0-5). For the majority of patients (n = 41, 55%) R-223 was the last treatment received. The most common treatments following R-223 were taxane chemotherapies (docetaxel, cabazitaxel) and antiandrogens (abiraterone, enzalutamide). We stratified patients based on pre-treatment hemoglobin levels and found that those with hemoglobin levels below the mean had a statistically increased risk of death (HR 1.99 95% CI 1.02-3.86). In our analysis of patterns of utilization of R-223 at a single NCCN and NCI member institution we found that R-223 tends to be utilized as a later line agent for patients with metastatic prostate cancer and is often one of the last treatments they receive. We also found that early receipt of R-223 and higher pre-treatment hemoglobin levels were correlated with better survival outcomes. Given these findings, and the favorable side-effect profile of radium-223 reported on the ALSYMPCA trial relative to the placebo group, consideration should be given to using R-223 early in the course of therapy for patients with metastatic prostate cancer with bone disease.