title: Gleason pattern 5 is the greatest risk factor for clinical failure and death from prostate cancer after dose-escalated radiation therapy and hormonal ablation.
abstract: OBJECTIVE
  The division of Gleason score (GS) into three categories (2-6, 7, 8-10) may not fully use its prognostic power, as revealed by recent reports demonstrating the presence of Gleason Pattern 5 (GP5) as a strong predictor for biochemical recurrence. Therefore, we analyzed the clinical outcomes in patients treated with dose-escalated radiation therapy (RT) based on the presence or absence of GP5.
  
  
  METHODS
  Outcomes were analyzed for 718 men treated for localized prostate cancer with external-beam RT to a minimum planning target volume dose of at least 75 Gy. We assessed the impact of GP5 and that of pretreatment- and treatment-related factors on freedom from biochemical failure, freedom from metastasis (FFM), cause-specific survival (CSS), and overall survival (OS).
  
  
  RESULTS
  At biopsy, 89% of patients had no GP5, and 11% (76/718) had GP5. There were no differences in age, comorbid illness, T stage, prostate-specific antigen, or the use or duration of androgen deprivation therapy between GS8 without GP5 and GS8-10 with GP5. The presence of GP5 predicted lower FFM (p < 0.002; hazard ratio [HR] 3.4 [1.7-7.1]); CSS (p < 0.0001; HR 12.9 [5.4-31]); and OS (p < 0.0001; HR 3.6 [2.0-6.5]) in comparison with GS8 (without GP5). The 8-year FFM, CSS, and OS were 89%, 98%, and 57%, respectively, for those with Gleason 8 prostate cancer without GP5 in comparison with 61%, 55%, and 31%, respectively, for those with GP5. In addition, both FFM and CSS were strongly influenced by androgen deprivation therapy given concurrently with RT. On multivariate analysis, GP5 was the strongest prognostic factor for all clinical endpoints, including OS.
  
  
  CONCLUSIONS
  The presence of GP5 predicts for worse clinical behavior, which therefore needs to be accounted for by risk stratification schemes. Further intensification of local and/or systemic therapy may be appropriate for such patients.
authors.affiliation: The University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Sabolch
authors.forename: Felix Y
authors.initials: FY
authors.lastname: Feng
authors.forename: Stephanie
authors.initials: S
authors.lastname: Daignault-Newton
authors.forename: Schuyler
authors.initials: S
authors.lastname: Halverson
authors.forename: Kevin
authors.initials: K
authors.lastname: Blas
authors.forename: Laura
authors.initials: L
authors.lastname: Phelps
authors.forename: Karin B
authors.initials: KB
authors.lastname: Olson
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Hamstra
mesh_terms: D000368:Aged; D000704:Analysis of Variance; D000726:Androgen Antagonists / Q000627:therapeutic use; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D012307:Risk Factors; D017211:Treatment Failure
chemical_list: D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen