title: Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours.
abstract: OBJECTIVE
  • To determine the influence of tumour and prostate gland volumes on the underestimation of prostate cancer Gleason score in diagnostic core biopsies.
  
  
  METHODS
  • Patients undergoing radical prostatectomy with matched diagnostic biopsies were identified from a prospectively recorded database. • Tumour volumes were measured in serial whole-mount sections with image analysis software as part of routine histological assessment. • Differences in various metrics of tumour and prostate volume between upgraded tumours and tumours concordant for the lower or higher grade were analysed.
  
  
  RESULTS
  • In all, 684 consecutive patients with Gleason score 6 or 7 prostate cancer on diagnostic biopsy were identified. • Of 298 patients diagnosed with Gleason 6 tumour on biopsy, 201 (67.4%) were upgraded to Gleason 7 or higher on final pathology. Similarly, of 262 patients diagnosed with Gleason 3 + 4 = 7 prostate cancer on initial biopsy, 60 (22.9%) were upgraded to Gleason score 4 + 3 = 7 or higher. • Tumours upgraded from Gleason 6 to 7 had a significantly lower index tumour volume (1.73 vs 2 mL, P= 0.029), higher calculated prostate volume (41.6 vs 39 mL, P= 0.017) and lower relative percentage of tumour to benign glandular tissue (4.3% vs 5.9%, P= 0.001) than tumours concordant for the higher grade. • Similarly, tumours that were Gleason score 3 + 4 on biopsy and upgraded on final pathology to 4 + 3 were significantly smaller as measured by both total tumour volume (2.3 vs 3.3 mL, P= 0.005) and index tumour volume (2.2 vs 3, P= 0.027) and occupied a smaller percentage of the gland volume (6.3% vs 8.9%, P= 0.017) compared with tumours concordant for the higher grade. • On multivariate analysis, lower prostate weight (hazard ratio 0.97, 95% confidence interval 0.96-0.99, P < 0.001) and larger total tumour volume (hazard ratio 1.87, 95% confidence interval 1.4-2.6, P < 0.001) independently predicted an upgrade in Gleason score from 6 to 7. In tumours upgraded from biopsy Gleason 3 + 4, only higher index tumour volume (hazard ratio 3.1, 95% confidence interval 1.01-9.3, P= 0.048) was a significant predictor of upgrading on multivariate analysis.
  
  
  CONCLUSIONS
  • Under-graded tumours are significantly smaller than tumours concordant for the higher grade, indicating that incomplete tumour sampling plays a significant role in Gleason score assignment error. • Surrogate measures of tumour volume may predict those at greatest risk of Gleason score upgrade.
authors: Prostate Centre at Vancouver General Hospital, Vancouver, BC, Canada. niallmcorcoran@gmail.com
authors: Niall M
authors: NM
authors: Corcoran
authors: Chris M
authors: CM
authors: Hovens
authors: Matthew K H
authors: MK
authors: Hong
authors: John
authors: J
authors: Pedersen
authors: Rowan G
authors: RG
authors: Casey
authors: Stephen
authors: S
authors: Connolly
authors: Justin
authors: J
authors: Peters
authors: Laurence
authors: L
authors: Harewood
authors: Martin E
authors: ME
authors: Gleave
authors: S Larry
authors: SL
authors: Goldenberg
authors: Anthony J
authors: AJ
authors: Costello
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000473:pathology*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D015983:Selection Bias; D047368:Tumor Burden