Early alkaline phosphatase dynamics as biomarker of survival in metastatic castration-resistant prostate cancer patients treated with radium-223

Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3325-3334. doi: 10.1007/s00259-021-05283-6. Epub 2021 Mar 8.


Purpose: Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS).

Methods: This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate.

Results: A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5-15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73-3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients.

Conclusion: Early treatment-induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.

Keywords: Alkaline phosphatase; Biomarker; Bone metastases; Castration-resistant prostate cancer; Prognostic variables; Radium-223.

Publication types

  • Multicenter Study

MeSH terms

  • Alkaline Phosphatase
  • Biomarkers
  • Bone Neoplasms* / radiotherapy
  • Humans
  • Male
  • Prostatic Neoplasms, Castration-Resistant* / radiotherapy
  • Radium* / therapeutic use
  • Retrospective Studies
  • Treatment Outcome


  • Biomarkers
  • Radium-223
  • Alkaline Phosphatase
  • Radium