title: A Contemporary Prostate Cancer Grading System: A Validated Alternative to the Gleason Score.
abstract: BACKGROUND
  Despite revisions in 2005 and 2014, the Gleason prostate cancer (PCa) grading system still has major deficiencies. Combining of Gleason scores into a three-tiered grouping (6, 7, 8-10) is used most frequently for prognostic and therapeutic purposes. The lowest score, assigned 6, may be misunderstood as a cancer in the middle of the grading scale, and 3+4=7 and 4+3=7 are often considered the same prognostic group.
  
  
  OBJECTIVE
  To verify that a new grading system accurately produces a smaller number of grades with the most significant prognostic differences, using multi-institutional and multimodal therapy data.
  
  
  METHODS
  Between 2005 and 2014, 20,845 consecutive men were treated by radical prostatectomy at five academic institutions; 5501 men were treated with radiotherapy at two academic institutions.
  
  
  METHODS
  Outcome was based on biochemical recurrence (BCR). The log-rank test assessed univariable differences in BCR by Gleason score. Separate univariable and multivariable Cox proportional hazards used four possible categorizations of Gleason scores.
  
  
  CONCLUSIONS
  In the surgery cohort, we found large differences in recurrence rates between both Gleason 3+4 versus 4+3 and Gleason 8 versus 9. The hazard ratios relative to Gleason score 6 were 1.9, 5.1, 8.0, and 11.7 for Gleason scores 3+4, 4+3, 8, and 9-10, respectively. These differences were attenuated in the radiotherapy cohort as a whole due to increased adjuvant or neoadjuvant hormones for patients with high-grade disease but were clearly seen in patients undergoing radiotherapy only. A five-grade group system had the highest prognostic discrimination for all cohorts on both univariable and multivariable analysis. The major limitation was the unavoidable use of prostate-specific antigen BCR as an end point as opposed to cancer-related death.
  
  
  CONCLUSIONS
  The new PCa grading system has these benefits: more accurate grade stratification than current systems, simplified grading system of five grades, and lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.
  
  
  RESULTS
  We looked at outcomes for prostate cancer (PCa) treated with radical prostatectomy or radiation therapy and validated a new grading system with more accurate grade stratification than current systems, including a simplified grading system of five grades and a lowest grade is 1, as opposed to 6, with the potential to reduce overtreatment of PCa.
authors.affiliation: The Johns Hopkins Medical Institutions, Baltimore, MD, USA. Electronic address: jepstein@jhmi.edu.
authors.forename: Jonathan I
authors.initials: JI
authors.lastname: Epstein
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Sjoberg
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Joel B
authors.initials: JB
authors.lastname: Nelson
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Egevad
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Cristina
authors.initials: C
authors.lastname: Magi-Galluzzi
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Vickers
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
authors.forename: Anil V
authors.initials: AV
authors.lastname: Parwani
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Samson W
authors.initials: SW
authors.lastname: Fine
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Eastham
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Wiklund
authors.affiliation: The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: Misop
authors.initials: M
authors.lastname: Han
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Chandana A
authors.initials: CA
authors.lastname: Reddy
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Jay P
authors.initials: JP
authors.lastname: Ciezki
authors.affiliation: Karolinska Institute, Stockholm, Sweden.
authors.forename: Tommy
authors.initials: T
authors.lastname: Nyberg
authors.affiliation: Cleveland Clinic, Cleveland, OH, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
mesh_terms: D000368:Aged; D003661:Decision Support Techniques; D006801:Humans; D007610:Kallikreins / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading / Q000379:methods*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000628:therapy; D011878:Radiotherapy; D015203:Reproducibility of Results; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen
keywords: Gleason grade; Gleason score