title: Independent validation of the prognostic capacity of the ISUP prostate cancer grade grouping system for radiation treated patients with long-term follow-up.
abstract: There has been a recent proposal to change the grading system of prostate cancer into a five-tier grade grouping system. The prognostic impact of this has been demonstrated in regards only to biochemical recurrence-free survival (bRFS) with short follow-up (3 years).
  
  
  
  Between 1990 and 2013, 847 consecutive men were treated with definitive external beam radiation therapy at a single academic center. To validate the new grade grouping system, bRFS, distant metastases-free survival (DMFS) and prostate cancer-specific survival (PCSS) were calculated. Adjusted Kaplan-Meier and multivariable Cox regression analyses were performed to assess the independent impact of the new grade grouping system. Discriminatory analyses were performed to compare the commonly used three-tier Gleason score system (6, 7 and 8-10) to the new system.
  
  
  
  The median follow-up of our cohort was 88 months. The 5-grade groups independently validated differing risks of bRFS (group 1 as reference; adjusted hazard ratio (aHR) 1.35, 2.16, 1.79 and 3.84 for groups 2-5, respectively). Furthermore, a clear stratification was demonstrated for DMFS (aHR 2.03, 3.18, 3.62 and 13.77 for groups 2-5, respectively) and PCSS (aHR 3.00, 5.32, 6.02 and 39.02 for groups 2-5, respectively). The 5-grade group system had improved prognostic discrimination for all end points compared with the commonly used three-tiered system (that is, Gleason score 6, 7 and 8-10).
  
  
  
  In a large independent radiotherapy cohort with long-term follow-up, we have validated the bRFS benefit of the proposed five-tier grade grouping system. Furthermore, we have demonstrated that the system is highly prognostic for DMFS and PCSS. Grade group 5 had markedly worse outcomes for all end points, and future work is necessary to improve outcomes in these patients.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: D E
authors.initials: DE
authors.lastname: Spratt
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: W C
authors.initials: WC
authors.lastname: Jackson
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A
authors.initials: A
authors.lastname: Abugharib
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S A
authors.initials: SA
authors.lastname: Tomlins
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Dess
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: P D
authors.initials: PD
authors.lastname: Soni
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: S G
authors.initials: SG
authors.lastname: Zhao
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: A I
authors.initials: AI
authors.lastname: Cole
authors.affiliation: Cedars-Sinai Medical Center, Department of Radiation Oncology, Los Angeles, CA, USA.
authors.forename: Z S
authors.initials: ZS
authors.lastname: Zumsteg
authors.affiliation: Cedars-Sinai Medical Center, Department of Radiation Oncology, Los Angeles, CA, USA.
authors.forename: H
authors.initials: H
authors.lastname: Sandler
authors.affiliation: Texas Oncology, Dallas, TX, USA.
authors.forename: D
authors.initials: D
authors.lastname: Hamstra
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Hearn
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: G
authors.initials: G
authors.lastname: Palapattu
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: R
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Morgan
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: F Y
authors.initials: FY
authors.lastname: Feng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading / Q000379:methods* / Q000592:standards; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000532:radiotherapy; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant; D016896:Treatment Outcome