Real world lessons for optimal selection of patients with bone metastatic castration-resistant prostate cancer for radium-223 therapy

By: Van Der Doelen M.J.1, Kuppen M.C.P.2, Jonker M.A.3, Janssen M.J.R.4, Mehra N.2, Van Oort I.M.1, Gerritsen W.R.2
Institutes: 1Radboudumc, Dept. of Urology, Nijmegen, The Netherlands, 2Radboudumc, Dept. of Medical Oncology, Nijmegen, The Netherlands, 3Radboudumc, Dept. of Health Evidence, Nijmegen, The Netherlands, 4Radboudumc, Dept. of Radiology and Nuclear Medicine, Nijmegen, The Netherlands

Introduction & Objectives

Radium-223 (Ra223) is a registered therapy for bone metastatic castration-resistant prostate cancer (CRPC), with a proven overall survival (OS) benefit of 3.6 months. There is a need for more clinical data to define which variables are associated with the OS benefit of Ra223 therapy. The aim of this study was to identify pre-therapeutic variables associated with OS in patients treated with Ra223.

Material & Methods

Data from 45 CRPC patients treated with Ra223 were retrospectively analyzed. All patients who received at least one Ra223 injection were included in the study. Cox proportional hazard regression models were used to estimate hazard ratio’s (HR) and to test for association.


Median age at start of Ra223 therapy was 71 years (range 51-84) and median follow-up was 13 months (range 1-38). At time of analysis, 38 (84%) patients had died. Median OS since start of Ra223 was 13.0 months (95% CI 8.2-17.8).
Univariable analysis showed poor baseline ECOG performance status (PS), baseline opioid use, lowered baseline hemoglobin, and elevated prostate-specific antigen, alkaline phosphatase and lactate dehydrogenase (LD) levels were significantly associated with OS. Multivariable Cox regression analysis demonstrated that poor baseline ECOG PS (HR 10.6) and high LD levels (HR 7.7) were pre-therapeutic variables that predicted poor OS (table 1).
The median number of injections was five; 21 patients (47%) received 6 injections, 24 patients (53%) received 1-5 injections. Patients who completed Ra223 therapy had a median OS of 19.7 months (95% CI 14.9-24.6), while patients who received one to five injections had a median OS of 5.9 months (95% CI 3.8-8.1; P < 0.001; figure 1). We found significant differences between patients who received 1-5 injections and those who completed therapy regarding baseline LD levels, baseline opioid use and prior use of abiraterone or enzalutamide. 

Table 1. Multivariable Cox regression analysis

Variable n Hazard Ratio 95% CI p
Prior abiraterone or enzalutamide (yes vs no) 32 2.38 0.91-6.23 0.08
ECOG performance score (0 vs 1) 26 10.62 3.07-36.73 <0.01
ECOG performance score (0 vs 2-3) 23 5.67 1.74-18.47 <0.01
Log lactace dehydrogenase 32 7.67 1.75-33.53 <0.01

Figure 1.


In a multivariable Cox regression model, good baseline ECOG PS and low LD levels were significantly associated with longer OS in patients treated with Ra223. These variables may be used for stratification of CRPC patients for Ra223 therapy. Prospective studies to evaluate these variables are warranted, to develop a nomogram to select patients properly.

  • Event: 9th European Multidisciplinary congress on Urological Cancers
  • Type: Abstract
  • Date: 16-11-2017
  • Views: 518
  • Nr: P049