Last reviewed: December 2018
Last updated: September  2018
28 Sep 2018

Safety concerns prompt EMA to restrict the use of radium-223 in metastatic prostate cancer

New restrictions have been placed on the use of radium-223 for the treatment of metastatic prostate cancer following a safety review by the European Medicines Agency (EMA). The review concluded that the use of radium-223 is associated with an increased risk of fractures and a possible increased risk of death.

The EMA has imposed the following new restrictions on the use of radium-223:

  • Restrict use to patients who have received two prior treatments for metastatic prostate cancer, or who cannot receive other treatments

  • Do not use with abiraterone and prednisolone (this combination is contraindicated)

  • Do not use with other systemic cancer therapies (except hormone therapy)

  • Do not use in asymptomatic patients (in line with its current indication)

  • Do not use in patients with a low number of osteoblastic bone metastases.

The safety review was prompted by findings from a phase III trial (ERA-223) comparing radium-223 in combination with abiraterone and prednisolone against placebo in combination with abiraterone and prednisolone in patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. Patients given combination treatment with radium-223 were found to be at risk of dying earlier (2.6 months earlier on average) and at greater risk of fractures (28.6% versus 11.4%) compared with patients given placebo.

The EMA said the higher risk of fractures may be due to the accumulation of radium-223 in areas of the bone that have already been damaged (e.g., by osteoporosis). However, the reasons for the possible earlier death seen in the trial are not fully understood.

See Management: approach See Management: treatment algorithm

Original source of update



History and exam

Key diagnostic factors

  • presence of risk factors
  • elevated prostate-specific antigen (PSA)

Other diagnostic factors

  • nocturia
  • urinary frequency
  • urinary hesitancy
  • dysuria
  • abnormal digital rectal examination
  • haematuria
  • weight loss/anorexia
  • lethargy
  • bone pain
  • palpable lymph nodes

Risk factors

  • age >50 years
  • black ethnicity
  • North American or northwest European descent
  • family history of prostate cancer
  • high levels of dietary fat

Diagnostic investigations

1st investigations to order

  • serum prostate-specific antigen (PSA)
  • testosterone
  • LFTs
  • FBC
  • renal function
  • prostate biopsy
Full details

Investigations to consider

  • bone scan
  • plain x-rays
  • pelvic CT scan
  • pelvic MRI/endorectal MRI
Full details

Emerging tests

  • urinary biomarkers
  • serum biomarkers
  • 18F-sodium fluoride PET/CT and 11C-choline PET/CT
  • prostate cancer antigen 3 (PCA3) assay
  • TMPRSS2-ERG gene fusions
  • prostate health index (PHI)
  • 4Kscore test
Full details

Treatment algorithm


Authors VIEW ALL

Radiation Oncologist

Richmond Radiation Oncology Associates

Bon Secours Cancer Institute




TJW declares that he is the principal investigator of an R-21 NIH research grant investigating the tumour-mediated immune responses in African-American men with prostate cancer.


Department of Radiation Oncology

University of Texas MD Anderson Cancer Center




MSA declares that he has no competing interests.

Peer reviewers VIEW ALL

Clinical Oncology Registrar

St Luke's Cancer Centre

Royal Surrey Hospital





EA has received consultation fees from the following organisations during the past 3 years: Blue Cross/Blue Shield Association, Sanofi-Aventis, Ferring Pharmaceuticals, Pfizer Corporation, American Urological Association, National Institutes of Health, Accreditation Council for Graduate Medical Education, Royal Hallamshire Hospital, Hartford County Medical Association. EA owns shares in Pfizer Pharmaceuticals, Johnson and Johnson, and General Electric Corporation.

Medical Director

UConn Medical Group

University of Connecticut Health Center




PA declares that he has no competing interests.

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