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CC BY-NC-ND 4.0 · World J Nucl Med 2021; 20(02): 139-144
DOI: 10.4103/wjnm.WJNM_74_20
Original Article

Quantifying the survival benefit of completing all the six cycles of radium-223 therapy in patients with castrate-resistant prostate cancer with predominant bone metastases

John Buscombe
1   Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK
,
Daniel Gillett
1   Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK
,
Nick Bird
1   Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK
,
Anne Powell
1   Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK
,
Sarah Heard
1   Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK
,
Luigi Aloj
1   Department of Nuclear Medicine, Cambridge University Hospitals, Cambridge, UK
2   Department of Nuclear Medicine, Cambridge University Hospitals; Department of Radiology, University of Cambridge, Cambridge, UK
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Abstract

A retrospective analysis was performed of epidemiological data assessing the survival of patients who had received radium-223 for castrate-resistant metastatic prostate cancer treated at a regional tertiary referral center over a 5-year period. The patients' age, date of first treatment, and the number of cycles of radium-223 given were obtained from the patients' electronic patient record (EPR). Data on the date of death were provided by national death registrations which update the EPR via a unique national health service number. A total of 187 patients (mean age on the date of first treatment: 73 years; range: 56–93) were treated from April 1, 2014, to June 30, 2019. The median overall survival of the 119 patients (71%) who had died by December 31, 2019, was 15 months. There was no significant age difference between those who had died and survivors (72 vs. 74 years). On a further analysis, it was found that the median overall survival of the 107 patients who had received all the six cycles of radium-223 was 31 months, significantly longer than the median overall survival of only 6 months for those eighty patients who had received less than the full course of six cycles of radium-223 (P = 0.001). Of those who received all the six cycles of treatment, 58 patients had died (58%) and the 1-year survival was 87%. This was compared to the group of patients receiving <6 cycles of radium-223 where 61 patients (76%) had died and the 1-year survival was 30%. Therefore, the hazard ratio of dying before 1 year if the patient did not receive all the six cycles of treatment was 2.9. Where the reason for stopping treatment was recorded on the EPR the most common cause for the cessation of treatment was because of the side effects caused by the treatment itself. Other causes were hospitalization with comorbidities, disease progression, or patient choice. Given the survival advantage of receiving the full course of all the six cycles of treatment, this should be administered if possible and the patients should be managed in such a way as to allow the complete treatment course to be given.

Keywords

Carcinoma of the prostate - median overall survival - radium-223

Financial support and sponsorship

Nil.




Publication History

Received: 11 August 2020

Accepted: 12 August 2020

Article published online:
24 March 2022

© 2021. Sociedade Brasileira de Neurocirurgia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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  • References

  • 1 Sharifi N, Dahut WL, Figg WD Secondary hormonal therapy for prostate cancer: What lies on the horizon? BJU Int 2008;101:271-4.
  • 2 Harzstark AL, Ryan CJ. Therapies in development for castrate-resistant prostate cancer. Expert Rev Anticancer Ther 2008;8:259-68.
  • 3 Abouassaly R, Paciorek A, Ryan CJ, Carroll PR, Klein EA. Predictors of clinical metastasis in prostate cancer patients receiving androgen deprivation therapy: Results from CaPSURE. Cancer 2009;115:4470-6.
  • 4 Nightengale B, Brune M, Blizzard SP, Ashley-Johnson M, Slan S. Strontium chloride Sr 89 for treating pain from metastatic bone disease. J Health Syst Pharm 1995;52:2189-95.
  • 5 Cowan RJ, Chilton HM, Cooper MR, Ferree CR, Watson EE, Robinson RG. Hematologic depression following therapy with strontium-89 chloride. Clin Nucl Med 1986;11:845-6.
  • 6 Collins C, Eary JF, Donaldson G, Vernon C, Bush NE, Petersdorf S, et al. Samarium-153-EDTMP in bone metastases of hormone refractory prostate carcinoma: A phase I/II trial. J Nucl Med 1993;34:1839-44.
  • 7 Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, et al. Quadramet 424Sm10/11 Study Group. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology 2004;63:940-5.
  • 8 Sartor O, Reid RH, Bushnell DL, Quick DP, Ell PJ. Safety and efficacy of repeat administration of samarium Sm-153 lexidronam to patients with metastatic bone pain. Sartor. Cancer 2007;109:637-43.
  • 9 Terrisse S, Karamouza E, Parker CC, Sartor AO, James ND, Pirrie S, et al. Survival in men with bone metastases from castration-resistant prostate cancer treated with bone-targeting radioisotopes: A meta-analysis of individual patient data from randomized clinical trials. JAMA Oncol 2019;6:206-16.
  • 10 Cheetham PJ, Petrylak DP. Alpha particles as radiopharmaceuticals in the treatment of bone metastases: Mechanism of action of radium-223 chloride (Alpharadin) and radiation protection. Oncology (Williston Park) 2012;26:330-7, 341.
  • 11 Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, et al. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin Genitourin Cancer 2013;11:20-6.
  • 12 Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, et al. ALSYMPCA investigators alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med 2013;369:213-23.
  • 13 Radium-223 dichloride for treating hormone relapsed prostate cancer with bone metastases. National Institute for Health Care and Excellence; 2016. Available from: https://www.nice.org.uk/guidance/ta412. [Last accessed on 2020 Oct 05].
  • 14 Fosbøl MØ, Petersen PM, Kjaer A, Mortensen J. 223Ra therapy of advanced metastatic castration-resistant prostate cancer: Quantitative assessment of skeletal tumor burden for prognostication of clinical outcome and hematologic toxicity. J Nucl Med 2018;59:596-602.
  • 15 Parimi S, Tsang E, Alexander A, Mckenzie M, Bachand F, Sunderland K, et al. Population-based study of the use of radium 223 in metastatic castration-resistant prostate cancer: Factors associated with treatment completion. Can Urol Assoc J 2017;11:350-5.
  • 16 Parikh S, Murray L, Kenning L, Bottomley D, Din O, Dixit S, et al. Real-world outcomes and factors predicting survival and completion of radium 223 in Metastatic castrate-resistant prostate cancer. Clin Oncol (R Coll Radiol) 2018;3:548-55.
  • 17 Dadhania S, Alonzi R, Douglas S, Gogbashian A, Hughes R, Dalili D, et al. Single-centre experience of use of radium 223 with clinical outcomes based on number of cycles and bone marrow toxicity. Anticancer Res 2018;38:5423-7.
  • 18 Uemura H, Uemura H, Nagamori S, Wakumoto Y, Kimura G, Kikukawa H, et al. Three-year follow-up of a phase II study of radium-223 dichloride in Japanese patients with symptomatic castration-resistant prostate cancer and bone metastases. Int J Clin Oncol 2019;24:557-66.
  • 19 Badrising SK, Louhanepessy RD, van der Noort V, Coenen JLLM, Hamberg P, Beeker A, et al. A prospective observational registry evaluating clinical outcomes of Radium-223 treatment in a nonstudy population. Int J Cancer 2020;147:1143-51.
  • 20 Frantellizzi V, De Feo MS, Di Rocco A, Pontico M, Pani A, Farcomeni A, et al. Baseline quality of life predicts overall survival in patients with mCRPC treated with 223Ra-dichloride. Hell J Nucl Med 2020;23:12-20.
  • 21 Richmond PJ, Doeman AM, Busocmbe JR, Hilson AJ, Kaisary AV. Extent of disease in initial bone scan: An indicator of survival in prostate cancer patients. In: Taylor A, Nally JV, Thomeson H, editors. Radionuclides and Nephrourology. Reston, VA, USA: Society of Nuclear Medicine; 2000. P. 211-15.
  • 22 Parker CC, Coleman RE, Sartor O, Vogelzang NJ, Bottomley D, Heinrich D, et al. Three-year safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases from phase 3 randomized alpharadin in symptomatic prostate cancer trial. Eur Urol 2018;73:427-35.
  • 23 Huynh-Le MP, Shults RC, Connor MJ, Hattangadi-Gluth JA. Adverse events associated with radium-223 in metastatic prostate cancer: Disproportionality analysis of fda data reflecting worldwide utilization. Clin Genitourin Cancer 2020;18:192-20000.
  • 24 Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol 2019;20:408-19.
  • 25 Sternberg CN, Castellano D, Daugaard G, Géczi L, Hotte SJ, Mainwaring PN, et al. Abiraterone acetate for patients with metastatic castration-resistant prostate cancer progressing after chemotherapy: Final analysis of a multicentre, open-label, early-access protocol trial. Lancet Oncol 2014;15:1263-8.
  • 26 Todenhöfer T, Stenzl A, Hofbauer LC, Rachner TD. Targeting bone metabolism in patients with advanced prostate cancer: Current options and controversies. Int J Endocrinol 2015;2015:838202.
  • 27 Hurwitz M, Buscombe JR, Jacene HA, Klitzke AK, Lamonica D, Lu Y, et al. ACR-ACNM-ASTRO-SNMMI practice parameter for the performance of therapy with radium-223. Am J Clin Oncol 2020;43:539-44.