title: Interpatient variation in normal peripheral zone apparent diffusion coefficient: effect on the prediction of prostate cancer aggressiveness.
abstract: OBJECTIVE
  To determine the interpatient variability of prostate peripheral zone (PZ) apparent diffusion coefficient (ADC) and its effect on the assessment of prostate cancer aggressiveness.
  
  
  METHODS
  The requirement for institutional review board approval was waived. Intra- and interpatient variation of PZ ADCs was determined by means of repeated measurements of normal ADCs at three magnetic resonance (MR) examinations in a retrospective cohort of 10 consecutive patients who had high prostate-specific antigen levels and negative findings at transrectal ultrasonographically-guided biopsy. In these patients, no signs of PZ cancer were found at all three MR imaging sessions. The effect of interpatient variation on the assessment of prostate cancer aggressiveness was examined in a second retrospective cohort of 51 patients with PZ prostate cancer. Whole-mount step-section pathologic evaluation served as reference standard for placement of regions of interest on tumors and normal PZ. Repeated-measures analysis of variance was used to determine the significance of the interpatient variations in ADCs. Linear logistic regression was used to assess whether incorporating normal PZ ADCs improves the prediction of cancer aggressiveness.
  
  
  RESULTS
  Analysis of variance revealed that interpatient variability (1.2-2.0×10(-3) mm2/sec) was significantly larger than measurement variability (0.068×10(-3) mm2/sec±0.027 [standard deviation]) (P=.0058). Stand-alone tumor ADCs showed an area under the receiver operating characteristic curve (AUC) of 0.91 for discriminating low-grade versus high-grade tumors. Incorporating normal PZ ADC significantly improved the AUC to 0.96 (P=.0401).
  
  
  CONCLUSIONS
  PZ ADCs show significant interpatient variation, which has a substantial effect on the prediction of prostate cancer aggressiveness. Correcting this effect results in a significant increase in diagnostic accuracy.
authors.affiliation: Department of Radiology, Radboud University Nijmegen Medical Centre, Geert Grooteplein 10, 6525 GA Nijmegen, the Netherlands. g.litjens@rad.umcn.nl
authors.forename: Geert J S
authors.initials: GJ
authors.lastname: Litjens
authors.forename: Thomas
authors.initials: T
authors.lastname: Hambrock
authors.forename: Christina
authors.initials: C
authors.lastname: Hulsbergen-van de Kaa
authors.forename: Jelle O
authors.initials: JO
authors.lastname: Barentsz
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Huisman
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D019540:Area Under Curve; D001706:Biopsy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000473:pathology*; D012189:Retrospective Studies; D018084:Ultrasonography, Interventional
chemical_list: D017430:Prostate-Specific Antigen