title: Characteristics of modern Gleason 9/10 prostate adenocarcinoma: a single tertiary centre experience within the Republic of Ireland.
abstract: BACKGROUND
  The 2005 international society of urological pathology consensus statement on Gleason grading in prostate cancer revised Gleason scoring in clinical practice. The potential for grade migration with this refinement poses difficulties in interpreting historical series. We report the characteristics of a recent cohort of consecutive Gleason score 9 or 10 prostate cancers in our institution. The purpose of this study was to define the clinicopathologic variables and staging information for this high-risk population, and to identify whether traditional prostate staging techniques are adequate for this subcohort of men.
  
  
  METHODS
  A computational review of our pathology database was performed. Between May 2010 and September 2012, 1,295 consecutive biopsies were undertaken, 168 of which were high-grade tumours (12.97 %). This group were divided into two cohorts of which 84 (12.05 %) had a highest reported Gleason score of 9 (N = 79) or 10 (N = 5) and 84 were reported as Gleason 8. All biopsies were double-reported by pathologists with a special interest in uropathology.
  
  
  RESULTS
  Men diagnosed with a Gleason pattern 5 tumour were statistically far more likely to have advanced disease on direct rectal examination of the prostate compared with Gleason sum 8 tumours (p < 0.001) and a positive first-degree family history of prostate cancer (p < 0.001). Overall, Gleason sum 9/10 prostate cancers were also found to be statistically more aggressive than Gleason sum 8 tumours on TRUS core biopsy analysis with significantly higher levels of perineural invasion (p < 0.0001) and extracapsular extension (p = 0.001) as well as a higher levels of tumour found within the core biopsy sample. Those men diagnosed with Gleason pattern 5 prostate cancer also had radiological indicators of increased tumour aggressiveness compared with Gleason sum 8 cancer with respect to bone (p = 0.0002) and visceral (p = 0.044) metastases at presentation.
  
  
  CONCLUSIONS
  This series of Gleason score 9/10 prostate cancers serves to highlight the large disease burden, adverse pathologic features, and locally advanced nature of this aggressive subtype, which has previously been under-described in the literature, and differs from historical series in having a large high-grade cohort demonstrating high rates of metastatic disease. A history of prostate cancer amongst first-degree relatives was particularly prevalent in this population raising the issue of screening in a high-risk population. The high incidence of visceral metastatic disease at presentation supports upfront staging with CT thorax, abdomen, and pelvis in patients with Gleason 9 or 10 prostate cancers.
authors.affiliation: Department of Urology, Cork/Mercy University Hospitals, Cork, Ireland, fokelly@rcsi.ie.
authors.forename: F
authors.initials: F
authors.lastname: O'Kelly
authors.forename: S
authors.initials: S
authors.lastname: Elamin
authors.forename: A
authors.initials: A
authors.lastname: Cahill
authors.forename: P
authors.initials: P
authors.lastname: Aherne
authors.forename: J
authors.initials: J
authors.lastname: White
authors.forename: J
authors.initials: J
authors.lastname: Buckley
authors.forename: K N
authors.initials: KN
authors.lastname: O'Regan
authors.forename: A
authors.initials: A
authors.lastname: Brady
authors.forename: D G
authors.initials: DG
authors.lastname: Power
authors.forename: M F
authors.initials: MF
authors.lastname: O'Brien
authors.forename: P
authors.initials: P
authors.lastname: Sweeney
authors.forename: N
authors.initials: N
authors.lastname: Mayer
authors.forename: P J
authors.initials: PJ
authors.lastname: Kelly
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology*; D000368:Aged; D001706:Biopsy; D006801:Humans; D015994:Incidence; D007494:Ireland; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D012189:Retrospective Studies; D062606:Tertiary Care Centers