title: Impact of a tertiary Gleason pattern 4 or 5 on clinical failure and mortality after radical prostatectomy for clinically localised prostate cancer.
abstract: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that a tertiary Gleason grade pattern 4 or 5 found in RP specimens has a negative impact on recurrence rate regarding biochemical relapse after radical prostatectomy. This is the first publication addressing clinical outcome in patients with a tertiary Gleason grade pattern 4 or 5 showing a negative influence on clinical failure rates.
  
  
  OBJECTIVE
  To investigate the impact of a tertiary Gleason grade (TGG) pattern 4 or 5 on clinical failure, as the presence of a TGG pattern 4 or 5 in radical prostatectomy (RP) specimens has been associated with biochemical failure.
  
  
  METHODS
  In all, 151 consecutive patients undergoing RP between 1985 and 2006 were reviewed, and 148 patients met study inclusion criteria. The RP specimens were pathologically re-examined and the presence of a TGG pattern 4 or 5 was recorded. The endpoint was clinical failure defined as local recurrence and/or development of metastasis at a mean follow-up of 108 months. Univariate analyses were performed using the Kaplan-Meier method. Multivariate analyses were performed using Cox proportional hazards regression.
  
  
  RESULTS
  Clinical failure was more likely among men with presence of a TGG pattern 4 or 5 than in men without a TGG pattern 4 or 5 (P= 0.006). In the subgroup of patients with Gleason score 7 the presence of a TGG 5 was significantly associated with clinical failure rate (P= 0.002). In patients with Gleason score <7 or >7, a TGG pattern 4 or 5 was not associated with increased failure rates. Multivariate Cox regression analyses in patients with Gleason score 7 showed that a TGG pattern 5 was a statistically significant predictor of clinical failure when adjusting for pathological stage, surgical margin status, extraprostatic extension and seminal vesicle invasion (hazard ratio 4.03, 95% confidence interval 1.72-9.46; P= 0.001). Further subgroup analyses showed that a TGG pattern 5 was associated with statistically higher clinical progression rates in patients with Gleason score 3 + 4 (P= 0.03). In patients with Gleason score 4 + 3, a TGG pattern 5 was associated with a trend towards a higher clinical progression rate, although this was not statistically significant (P= 0.189).
  
  
  CONCLUSIONS
  A TGG pattern 4 or 5 is associated with decreased clinical recurrence-free survival in Gleason score 7.
authors.affiliation: Departments of Pathology Surgery, The Norwegian Radium Hospital, Oslo, Norway. einar.servoll@sshf.no
authors.forename: Einar
authors.initials: E
authors.lastname: Servoll
authors.forename: Thorstein
authors.initials: T
authors.lastname: Saeter
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Vlatkovic
authors.forename: Tormod
authors.initials: T
authors.lastname: Lund
authors.forename: Jahn
authors.initials: J
authors.lastname: Nesland
authors.forename: Gudmund
authors.initials: G
authors.lastname: Waaler
authors.forename: Karol
authors.initials: K
authors.lastname: Axcrona
authors.forename: Hans O
authors.initials: HO
authors.lastname: Beisland
mesh_terms: D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods*; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009664:Norway / Q000453:epidemiology; D011379:Prognosis; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery; D012189:Retrospective Studies; D015996:Survival Rate / Q000639:trends; D017211:Treatment Failure