title: The CT flare response of metastatic bone disease in prostate cancer.
abstract: BACKGROUND
  New or worsening bone lesions in patients responding to treatment, known as the flare phenomenon is well described on (99m)Tc-MDP bone scintigraphy, but to our knowledge has not previously been described on CT. The appearance of new or worsening bone sclerosis on CT in patients with prostate cancer may therefore be erroneously classified as disease progression.
  
  
  OBJECTIVE
  To assess the incidence of osteoblastic healing flare response at 3-month CT assessment in patients with castrate-resistant prostate cancer and to identify associated features that enable differentiation from progressive metastatic bone disease at 3 months.
  
  
  METHODS
  CT scans of 67 patients with castrate-resistant prostate cancer undergoing treatment were reviewed by a radiologist blinded to clinical outcome. Changes in number, size, and density of metastatic bone lesions were documented and Response Evaluation Criteria in Solid Tumours (RECIST) in soft tissue lesions, alkaline phosphatase, prostate specific antigen, and (99m)Tc-MDP bone scans were used for correlation.
  
  
  RESULTS
  Of the 39 patients who had 3- and 6-month follow-up, eight patients (21%) demonstrated an increase in number, size, or density of sclerotic lesions on the 3-month CT scan despite improvement in PSA and soft tissue lesions. Three out of eight patients (8%) maintained partial response/remained stable at follow-up and were defined as showing a flare response: in this group bone metastases evident on CT showed a qualitative and quantitative increase in density and no lesions faded at 3 months. In contrast, in all patients who progressed at 3 months by PSA/RECIST criteria (n = 8) bone lesions showed a mixed pattern with some lesions increasing and others decreasing in density.
  
  
  CONCLUSIONS
  The incidence of flare response of metastatic bone disease evident at 3-month post-treatment CT in patients with prostate cancer undergoing systemic treatment is 8%. In patients with falling PSA and stable/responding soft tissue disease at 3 months an increase in bone sclerosis in the absence of fading bone metastases can be interpreted as flare and is likely to represent a response.
authors.affiliation: Cancer Research UK Clinical Magnetic Resonance Research Group, Institute of Cancer Research and Royal Marsden NHS Foundation Trust, Surrey, UK. Christina.Messiou@icr.ac.uk
authors.forename: Christina
authors.initials: C
authors.lastname: Messiou
authors.forename: Gary
authors.initials: G
authors.lastname: Cook
authors.forename: Alison H M
authors.initials: AH
authors.lastname: Reid
authors.forename: Gerhardt
authors.initials: G
authors.lastname: Attard
authors.forename: David
authors.initials: D
authors.lastname: Dearnaley
authors.forename: Johann S
authors.initials: JS
authors.lastname: de Bono
authors.forename: Nandita M
authors.initials: NM
authors.lastname: de Souza
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000032:analysis; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D003287:Contrast Media; D003937:Diagnosis, Differential; D018450:Disease Progression; D006801:Humans; D007472:Iohexol; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000000981:diagnostic imaging; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000473:pathology*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D018709:Statistics, Nonparametric; D013669:Technetium Tc 99m Medronate; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D019275:Radiopharmaceuticals; D007472:Iohexol; D000469:Alkaline Phosphatase; D017430:Prostate-Specific Antigen; D013669:Technetium Tc 99m Medronate