Pain response in a population-based study of radium-223 (Ra223) for metastatic castration-resistant prostate cancer

  • Sunil Parimi BC Cancer
  • Suraya Bondy
  • Erica Tsang
  • Michael Ross McKenzie
  • Francois Bachand
  • Maria Aparicio
  • Graeme Duncan
  • Katherine Sunderland
  • Robert Anton Olson
  • Howard Huaihan Pai
  • Abraham Skaria Alexander
  • Vincent LaPointe
  • Kim N. Chi
  • Scott Tyldesley
Keywords: Radium-223, pain response, metastatic castration resistant prostate cancer


Introduction: Clinical trials have shown that radium-223 (Ra223) can prolong survival and improve quality of life in patients with metastatic castration-resistant prostate cancer (mCRPC). The objectives of this study were to evaluate pain responses with Ra223 at a population-based level and to determine if there is an association between pain response and alkaline phosphatase (ALP) response.

Methods: All patients from the Vancouver and Kelowna Cancer Centers (CC) in British Columbia who were treated with Ra223 between June 2015 and December 2016 were identified. Patients completed the Brief Pain Inventory (BPI) just prior to each Ra223 injection. Pain response was defined as a two or more point improvement in worst pain relative to baseline, without an increase in pain medication level. ALP was determined at each visit, with a response threshold defined as a 30% decrease from baseline, consistent with the definition of response used in the ALSYMPCA trial.

Results: A total of 65 patients in Vancouver and Kelowna CC received Ra223 during the study period and 56 patients had at least one BPI record, of which 44 (79%) patients were assessable for change in worst pain. Of the assessable patients, 23 (52%, 95% confidence interval [CI] 38–67) had a pain response, although the use of concurrent external beam radiotherapy was a confounder in four cases. Of the 44 patients assessable for change in worst pain, 59% had ALP responses greater than 30%. An ALP response was seen in 56% of pain-responders vs. 43% of non-pain-responders. There was no association between pain response and ALP response (Phi =-0.05; p=0.77).

Conclusions: Ra223 administration was associated with a meaningful pain response rate in this cohort. There was no correlation between pain response and ALP response.

Author Biography

Sunil Parimi, BC Cancer
Medical Oncologist


Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23.

Nilsson S, Strang P, Aksnes AK, et al. A randomized, dose-response, multicenter phase II study of radium-223 chloride for the palliation of painful bone metastases in patients with castration-resistant prostate cancer. Eur J Cancer 2012;48(5):678-86.

Morris MJ, Sartor AO, Vogelzang NJ, et al. Effect of radium-223 dichloride (Ra-223) on pain from US EAP. J Clin Oncol. 33, 2015 (suppl 7; abstr 160).

Chow E, James J, Barsevick A et al. Confirmatory factor analysis of brief pain inventory (BPI) functional interference clusters in patients with bone metastases. J Pain Manag. 2010; 3(3): 247-53.

Sartor O, Coleman R, Nilsson S, et al. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol 2014;15:738-46.

Layde PM, Broste SK, Desbiens N, et al. Generalizability of clinical studies conducted at tertiary care medical centers: a population-based analysis. J Clin Epidemiol 1996;49(8):835-41.

Yusuf S, Collins R, and Peto R. Why do we need some large, simple randomized trials? Stat Med 1984;3:409-20.

Heinrich D, Bektic J, Bergman A, et al. The contemporary use of radium-223 in metastatic castration-resistant prostate cancer. Clin Genitourin Cancer 2017;[epub ahead of print].

Henriksen G, Breistol K, Bruland OS, et al. Significant antitumor effect from bone-seeking, alpha-particle-emitting (223)Ra demonstrated in an experimental skeletal metastases model. Cancer Res 2002;62:3120-5.

Bruland OS, Nilsson S, Fisher DR, et al. High-linear energy transfer irradiation targeted to skeletal metastases by the alpha-emitter 223Ra: adjuvant or alternative to conventional modalities? Clin Cancer Res 2006;12:6250s-7s.

Suominen MI, Fagerlund KM, Rissanen JP, et al. Radium-223 inhibits osseous prostate cancer growth by dual targeting of cancer cells and bone microenvironment in mouse models. Clin Cancer Res 2017;23:4335-46.

Nome R, Hernes E, Bogsrud TV, et al. Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223. Scand J Urol 2015;49(3):211-7.

Sprangers MA and Aaronson NK. The role of health care providers and significant others in evaluating the quality of life of patients with chronic disease: a review. J Clin Epidemiol 1992;45:743-60.

Saad F, Gleason DM, Murray R, et al. A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma. J Natl Cancer Inst 2002;94(19):1458-68.

Rodrigues P, Hering F, and Campagnari JC. Use of bisphosphonates can dramatically improve pain in advanced hormone-refractory prostate cancer patients. Prostate Cancer Prostatic Dis 2004;7:350-4.

Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011;377(9768):813-22.

Saad F, Carles J, Gillessen S, et al. Radium-223 and concomitant therapies in patients with metastatic castration-resistant prostate cancer: an international, early access, open-label, single-arm phase 3b trial. Lancet Oncol 2016;17(9):1306-16.

Sartor O, Vogelzang NJ, Sweeney C, et al. Radium-223 safety, efficacy, and concurrent use with abiraterone or enzalutamide: first U.S. experience from an Expanded Access Program. Oncologist 2017;[epub ahead of print].

How to Cite
Parimi, S., Bondy, S., Tsang, E., McKenzie, M. R., Bachand, F., Aparicio, M., Duncan, G., Sunderland, K., Olson, R. A., Pai, H. H., Alexander, A. S., LaPointe, V., Chi, K. N., & Tyldesley, S. (2018). Pain response in a population-based study of radium-223 (Ra223) for metastatic castration-resistant prostate cancer. Canadian Urological Association Journal, 13(10), E311-6.
Original Research