title: The relationship between preoperative prostate-specific antigen and biopsy Gleason sum in men undergoing radical retropubic prostatectomy: a novel assessment of traditional predictors of outcome.
abstract: OBJECTIVE
  To investigate the relationship between prostate-specific antigen (PSA) level and Gleason sum, and its impact on biochemical failure (persistent PSA level of >0.2 ng/mL) after radical prostatectomy (RP), as the PSA, Gleason sum and clinical stage are commonly used preoperative predictors of outcome in men with localized prostate cancer.
  
  
  METHODS
  The Columbia Urologic Oncology Database was reviewed (1988-2006); 3460 had undergone RP. Patients who received neoadjuvant/adjuvant therapy or had incomplete data were excluded, yielding 1932 in the analysed sample. Analysis of variance (ANOVA) methods were used to assess differences in PSA level (on a log scale) among three different groups of patients, categorized by their Gleason sum scores, as <7, 7 and >7. To account for full penetrance of PSA screening, surgery before 1998 was considered as a potential confounder. ANOVA was used to determine whether the association of Gleason score and PSA levels differed before and after 1998. The effect of PSA level on biochemical failure was examined for variance among the three Gleason score groups using a Cox proportional hazards model with time to biochemical failure as the outcome, logPSA, Gleason sum (<7, 7 and >7), their interaction, and clinical stage as the predictors. Concordance indices (c-index) were calculated for the model with and without the interaction term between PSA and Gleason sum to determine its significance.
  
  
  RESULTS
  Of 1932 patients, 1190 (61.6%) had a Gleason sum of <7, 595 (30.8%) of 7 and 146 (7.6%) of >7. The median PSA level was 5.9, 6.1 and 7.8 ng/mL, respectively (P < 0.001). After adjusting for clinical stage, there was no significant interaction effect (P = 0.34) between Gleason sum and time of surgery on PSA level, implying that the relationship between Gleason sum and PSA levels has not changed over these two periods, despite changes in PSA screening. Results from the Cox model showed that PSA level, Gleason sum, their interaction term and clinical stage were significant predictors of biochemical failure. The c-index for the model without the interaction term was 0.70 and increased to 0.72 when including it, indicating an increase in the predictive ability of the model when including the interaction term.
  
  
  CONCLUSIONS
  PSA level and Gleason sum are highly interrelated variables, although they each carry additional information that significantly contributes to the prediction of biochemical failure. This study shows that, for an individual patient, the higher the initial PSA level the higher the risk of having poorly differentiated prostate cancer. Also, predictive models of biochemical failure can be improved by considering the interaction between PSA and Gleason sum.
authors.affiliation: Department of Urology, Johns Hopkins University, Baltimore, MD 21287, USA. philpierorazio@jhmi.edu
authors.forename: Phillip
authors.initials: P
authors.lastname: Pierorazio
authors.forename: Manisha
authors.initials: M
authors.lastname: Desai
authors.forename: Tara
authors.initials: T
authors.lastname: McCann
authors.forename: Mitchell
authors.initials: M
authors.lastname: Benson
authors.forename: James
authors.initials: J
authors.lastname: McKiernan
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001707:Biopsy, Needle; D015331:Cohort Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011300:Preoperative Care; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood*; D011468:Prostatectomy / Q000379:methods*; D011471:Prostatic Neoplasms / Q000097:blood* / Q000473:pathology* / Q000601:surgery; D012307:Risk Factors
chemical_list: D017430:Prostate-Specific Antigen
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