title: Apparent diffusion coefficient as a predictive biomarker of prostate cancer progression: value of fast and slow diffusion components.
abstract: OBJECTIVE
  The purpose of our study was to investigate whether fast and slow components of the apparent diffusion coefficient (ADC) from diffusion-weighted MR images could predict prostate cancer progression in patients managed by active surveillance.
  
  
  METHODS
  Eighty-one patients managed by active surveillance underwent diffusion-weighted MRI in addition to T2-weighted MRI using an endorectal technique. ADCs from tumor regions of interest were calculated using all b values (ADC(all)), b = 0-300 s/mm(2) (ADC(fast)), and b = 300-800 s/mm(2) (ADC(slow)). These parameters and tumor volumes were compared in those upgraded at subsequent biopsy (n = 14) versus those histologically stable (n = 41) and in evaluable patients who progressed to radical treatment (n = 16) versus those who did not (n = 64). Cox's regression was used to analyze the effect of parameter mean on time to treatment.
  
  
  RESULTS
  ADC(all), ADC(fast), and ADC(slow) in patients upgraded on repeat biopsy were significantly lower than those who were stable (1,070 ± 110 vs 1,356 ± 357 × 10(-6)mm(2)/s, p < 0.001; 1,283 ± 188 vs 1,526 ± 397 × 10(-6)mm(2)/s, p = 0.004; 843 ± 74 vs 1,105 ± 285 × 10(-6) mm(2)/s, p < 0.001, respectively). Tumor volume was significantly higher in the upgraded group (0.86 ± 0.9 vs 0.26 ± 0.25 cm(3), p = 0.02). The lower ADC(slow) in patients who subsequently progressed to radical treatment approached significance (922 ± 256 vs 1,054 ± 235 × 10(-6) mm(2)/s, p = 0.053; hazard ratio, 0.991 for time to treatment). Tumor volume was significantly higher in the treated group (0.86 ± 0.85 cm(3) vs 0.32 ± 0.33 cm(3), p = 0.02). ADC(slow) and tumor volume were significant but independent predictors of upgrade on biopsy (p = 0.01 and 0.002, respectively).
  
  
  CONCLUSIONS
  Both fast and slow diffusion components were significantly lower in tumors that were subsequently upgraded on histology. Both tumor volume and the true diffusion ADC(slow) were significant but independent predictors of histologic progression.
authors.affiliation: Cancer Research UK Clinical MR Research Group, Institute of Cancer Research, Royal Marsden Hospital, Sutton, Surrey, United Kingdom.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Giles
authors.forename: Veronica A
authors.initials: VA
authors.lastname: Morgan
authors.forename: Sophie F
authors.initials: SF
authors.lastname: Riches
authors.forename: Karen
authors.initials: K
authors.lastname: Thomas
authors.forename: Christopher
authors.initials: C
authors.lastname: Parker
authors.forename: Nandita M
authors.initials: NM
authors.lastname: deSouza
mesh_terms: D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018450:Disease Progression; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D019047:Phantoms, Imaging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000473:pathology*; D018709:Statistics, Nonparametric
chemical_list: D015415:Biomarkers