title: Changes in prostate-specific antigen, markers of bone metabolism and bone scans after treatment with radium-223.
abstract: OBJECTIVE
  The aim of this study was to assess treatment-related changes in prostate-specific antigen (PSA), total and bone alkaline phosphatase (total ALP, bone ALP), and changes on conventional bone scans in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases who received six cycles of radium-223 (Ra-223).
  
  
  METHODS
  Changes in PSA, total ALP and bone ALP (≥30% increase or decrease), and changes on bone scans were assessed before and after six monthly cycles of Ra-223 therapy (50 kBq/kg body weight) in 14 patients with mCRPC with bone metastases and four patients on placebo.
  
  
  RESULTS
  Post-treatment PSA increased by at least 30% in 11 out of 14 patients and remained stable in three. Total ALP and bone ALP decreased in six and nine patients, respectively. In 10 out of 12 evaluable patients the uptake on post-treatment bone scan was reduced in lesions with high pretreatment uptake, in 11 patients accompanied by the development of new or expanded bone lesions. FACBC position emission tomography/computed tomography scans confirmed the growth of new or expanded bone metastases in two patients.
  
  
  CONCLUSIONS
  These observations support the notion that Ra-223 kills tumour cells in metastases surrounded by highly proliferating osteoblasts, consistent with the reported survival benefit. The radiation effect in small tumour deposits not surrounded by increased osteoblast activity seems, however, insufficient, thus allowing continuous tumour growth. Long-lasting PSA reductions are the exception rather than the rule during Ra-223 treatment, whereas alkaline phosphatases decrease more frequently. To improve the overall anticancer effect, Ra-223 might be a valuable component of combination treatment.
authors.affiliation: Department of Medical Biochemistry and.
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Nome
authors.forename: Eivor
authors.initials: E
authors.lastname: Hernes
authors.forename: Trond Velde
authors.initials: TV
authors.lastname: Bogsrud
authors.forename: Trine
authors.initials: T
authors.lastname: Bjøro
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fosså
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D014408:Biomarkers, Tumor / Q000097:blood; D001859:Bone Neoplasms / Q000532:radiotherapy* / Q000556:secondary; D001842:Bone and Bones / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D049268:Positron-Emission Tomography; D017430:Prostate-Specific Antigen / Q000097:blood*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011868:Radioisotopes / Q000627:therapeutic use; D011877:Radionuclide Imaging; D011878:Radiotherapy; D011883:Radium / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D014408:Biomarkers, Tumor; D011868:Radioisotopes; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: Alkaline phosphatases; PSA; bone scan; hormone-resistant metastatic prostate cancer