title: Multi-institutional validation of the prognostic value of Ki-67 labeling index in patients treated with radical prostatectomy.
abstract: OBJECTIVE
  Several smaller single-center studies have reported a prognostic role for Ki-67 labeling index in prostate cancer. Our aim was to test whether Ki-67 is an independent prognostic marker of biochemical recurrence (BCR) in a large international cohort of patients treated with radical prostatectomy (RP).
  
  
  METHODS
  Ki-67 immunohistochemical staining on prostatectomy specimens from 3,123 patients who underwent RP for prostate cancer was retrospectively performed. Univariable and multivariable Cox regression models were used to assess the association of Ki-67 status with BCR.
  
  
  RESULTS
  Ki-67 positive status was observed in 762 (24.4 %) patients and was associated with lymph node involvement (LNI) (p = 0.039). Six hundred and twenty-one (19.9 %) patients experienced BCR. The estimated 3-year biochemical-free survivals were 85 % for patients with negative Ki-67 status and 82.1 % for patients with positive Ki-67 status (log-rank test, p = 0.014). In multivariable analysis that adjusted for the effects of age, preoperative PSA, RP Gleason sum, seminal vesicle invasion, extracapsular extension, positive surgical margins, lymphovascular invasion, and LNI, Ki-67 was significantly associated with BCR (HR = 1.19; p = 0.019). Subgroup analysis revealed that Ki-67 is associated with BCR in patients without LNI (p = 0.004), those with RP Gleason sum 7 (p = 0.015), and those with negative surgical margins (p = 0.047).
  
  
  CONCLUSIONS
  We confirmed Ki-67 as an independent predictor of BCR after RP. Ki-67 could be particularly informative in patients with favorable pathologic characteristics to help in the clinical decision-making regarding adjuvant therapy and optimized follow-up scheduling.
authors.affiliation: Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tewari
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lucca
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.forename: Malte
authors.initials: M
authors.lastname: Rieken
authors.forename: Alexander
authors.initials: A
authors.lastname: Bachman
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.forename: Markus
authors.initials: M
authors.lastname: Margreiter
mesh_terms: D000328:Adult; D000368:Aged; D006801:Humans; D007150:Immunohistochemistry; D007610:Kallikreins / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D009367:Neoplasm Staging; D018365:Neoplasm, Residual; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012189:Retrospective Studies
chemical_list: D019394:Ki-67 Antigen; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen