title: Automated Bone Scan Index as a quantitative imaging biomarker in metastatic castration-resistant prostate cancer patients being treated with enzalutamide.
abstract: BACKGROUND
  Having performed analytical validation studies, we are now assessing the clinical utility of the upgraded automated Bone Scan Index (BSI) in metastatic castration-resistant prostate cancer (mCRPC). In the present study, we retrospectively evaluated the discriminatory strength of the automated BSI in predicting overall survival (OS) in mCRPC patients being treated with enzalutamide.
  
  
  METHODS
  Retrospectively, we included patients who received enzalutamide as a clinically approved therapy for mCRPC and had undergone bone scan prior to starting therapy. Automated BSI, prostate-specific antigen (PSA), hemoglobin (HgB), and alkaline phosphatase (ALP) were obtained at baseline. Change in automated BSI and PSA were obtained from patients who have had bone scan at week 12 of treatment follow-up. Automated BSI was obtained using the analytically validated EXINI Bone(BSI) version 2. Kendall's tau (τ) was used to assess the correlation of BSI with other blood-based biomarkers. Concordance index (C-index) was used to evaluate the discriminating strength of automated BSI in predicting OS.
  
  
  RESULTS
  Eighty mCRPC patients with baseline bone scans were included in the study. There was a weak correlation of automated BSI with PSA (τ = 0.30), with HgB (τ = -0.17), and with ALP (τ = 0.56). At baseline, the automated BSI was observed to be predictive of OS (C-index 0.72, standard error (SE) 0.03). Adding automated BSI to the blood-based model significantly improved the C-index from 0.67 to 0.72, p = 0.017. Treatment follow-up bone scans were available from 62 patients. Both change in BSI and percent change in PSA were predictive of OS. However, the combined predictive model of percent PSA change and change in automated BSI (C-index 0.77) was significantly higher than that of percent PSA change alone (C-index 0.73), p = 0.041.
  
  
  CONCLUSIONS
  The upgraded and analytically validated automated BSI was found to be a strong predictor of OS in mCRPC patients. Additionally, the change in automated BSI demonstrated an additive clinical value to the change in PSA in mCRPC patients being treated with enzalutamide.
authors.affiliation: Department of Translational Medicine, Division of Urological Cancers, Lund University, Waldenströms Gata 5, Malmö, SE 205 02, Sweden. aseem.anand@med.lu.se.|Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. aseem.anand@med.lu.se.
authors.forename: Aseem
authors.identifier: http://orcid.org/0000-0001-9452-6094
authors.initials: A
authors.lastname: Anand
authors.affiliation: Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA.|Weil Cornell Medical College, New York, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Morris
authors.affiliation: Weil Cornell Medical College, New York, USA.|Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Larson
authors.affiliation: Department of Radiation Physics, Skåne University Hospital, Lund University, Malmö, Sweden.
authors.forename: David
authors.initials: D
authors.lastname: Minarik
authors.affiliation: Department of Urology, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Josefsson
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: John T
authors.initials: JT
authors.lastname: Helgstrand
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Oturai
authors.affiliation: Department of Nuclear Medicine, Skåne University Hospital, Malmö, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Edenbrandt
authors.affiliation: Copenhagen Prostate Cancer Center, Department of Urology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Martin Andreas
authors.initials: MA
authors.lastname: Røder
authors.affiliation: Department of Translational Medicine, Division of Urological Cancers, Lund University, Waldenströms Gata 5, Malmö, SE 205 02, Sweden.|Department of Urology, Skåne University Hospital, Malmö, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
keywords: Bone Scan Index (BSI); Bone scan; Enzalutamide; Imaging biomarker; Metastatic castration-resistant prostate cancer (mCRPC)