223 Ra 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 Apr;59(4):596-602. doi: 10.2967/jnumed.117.195677. Epub 2017 Sep 1.


The aim of this study was to investigate the prognostic value of the quantitative assessment of skeletal tumor burden on bone scintigraphy (Bone Scan Index [BSI]) in patients who have advanced metastatic castration-resistant prostate cancer (mCRPC) and are receiving 223RaCl2 We hypothesized that the BSI can serve as a prognostic biomarker of overall survival (OS) and hematologic toxicity and as a tool for response assessment in patients with mCRPC treated with 223RaCl2Methods: This study was a retrospective investigation of a Danish cohort of mCRPC patients who received 223RaCl2 therapy between March 2014 and October 2015 and for whom baseline bone scintigraphy was available. Bone scintigraphy studies were reviewed and graded according to the extent of disease. Furthermore, an automated BSI (EXINI BoneBSI) was obtained for baseline scintigraphy studies and follow-up scans after 3 cycles as well as at the end of therapy. Clinical outcomes were OS and occurrence of hematologic toxicity of grades 2-5. Associations between the BSI and clinical outcomes were investigated in multivariate regression models including the visual assessment of bone scintigraphy and other relevant covariates. Results: A total of 88 patients were included. The median number of completed 223RaCl2 cycles was 4, and 27 patients (31%) completed 6 cycles. The BSI was significantly associated with OS in the multivariate analysis; the median OS for patients with a BSI of greater than 5 was 8.2 mo, and the median OS for patients with a BSI of less than or equal to 5 was 15.0 mo (hazard ratio, 2.65 [95% confidence interval, 1.5-4.71]; P = 0.001). Likewise, the baseline BSI was prognostic for the occurrence of hematologic toxicity; patients with a BSI of greater than 5 had an odds ratio of 3.02 (95% confidence interval, 1.2-7.8; P = 0.02) for toxicity. The BSI declined during therapy in 44% of the patients who completed 3 cycles of 223RaCl2 (n = 52) and in 84% of the patients after the end of therapy (n = 32). There was no significant association between a change in the BSI during therapy and OS. Conclusion: The BSI is a promising biomarker for prognostication of OS and hematologic toxicity in late-stage mCRPC patients receiving 223RaCl2 Further prospective studies are needed to evaluate the potential of the BSI for response assessment in 223RaCl2 therapy.

Keywords: 223Ra; bone scan index; bone scintigraphy; prostate cancer.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / diagnosis
  • Bone Neoplasms / pathology*
  • Bone Neoplasms / secondary*
  • Hematologic Tests*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prostatic Neoplasms, Castration-Resistant / blood
  • Prostatic Neoplasms, Castration-Resistant / pathology*
  • Prostatic Neoplasms, Castration-Resistant / radiotherapy*
  • Radium / therapeutic use*
  • Retrospective Studies
  • Tumor Burden / radiation effects*


  • Radium-223
  • Radium