title: Loss of AZGP1 as a Superior Predictor of Relapse in Margin-Positive Localized Prostate Cancer.
abstract: Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs. Our study aimed to determine whether the biomarkers AZGP1 expression and Gleason grade at the site of a PSM are significant independent markers of biochemical and clinical relapse (CR) when modeled together and whether one of these biomarkers may be superior in its capacity to predict outcome.
  
  
  
  A cohort of 275 consecutive patients with margin-positive localized PC following surgery were assessed for Gleason grade and AZGP1 expression at the PSM. BR-free survival was the primary end-point, while CR-free survival and PC-specific death were secondary endpoints. Kaplan-Meier Analysis and Cox Proportional Hazards Modeling were performed.
  
  
  
  Absent AZGP1 expression was significantly associated with increased risk of BR (P = 0.001) and PC-specific death (P = 0.02). Gleason grade ≥4 at PSM was associated with BR (P = 0.02), CR (P = 0.003), and PC-specific death (P = 0.004). On multivariable analysis, absent AZGP1 expression remained an independent predictor of BR (HR 2.4, 95%CI 1.5-3.9, P < 0.001) when modeled with Gleason grade at margin (HR 1.3, 95%CI 0.9-1.9, P = 0.16), preoperative PSA (P = 0.002), seminal vesicle involvement (P = 0.002), extraprostatic extension (P = 0.001), Gleason score (P = 0.01), adjuvant treatment (P = 0.75), linear length of the involved margin (P = 0.001) and margin number (P = 0.09).
  
  
  
  Absent AZGP1 expression is an independent predictor of BR in margin-positive localized PC and is associated with increased PC-specific mortality in a Phase II study. Absent AZGP1 expression was superior to Gleason grade at PSM in predicting relapse and should be incorporated into subsequent clinical trials of post-operative radiotherapy in men with margin-positive PC. Prostate 76:1491-1500, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.|University of New South Wales, Kensington, New South Wales, Australia.
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Bruce
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.|University of New South Wales, Kensington, New South Wales, Australia.|Department of Urology, St Vincent's Clinic, Darlinghurst, New South Wales, Australia.
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Stricker
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.|Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.|University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: Ruta
authors.initials: R
authors.lastname: Gupta
authors.affiliation: Department of Urology, St Vincent's Clinic, Darlinghurst, New South Wales, Australia.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Savdie
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
authors.forename: Anne-Maree
authors.initials: AM
authors.lastname: Haynes
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.|University of Sydney, Camperdown, New South Wales, Australia.|Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia.|Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Mahon
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.
authors.forename: Hui-Ming
authors.initials: HM
authors.lastname: Lin
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia.|Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia.|University of Sydney, Camperdown, New South Wales, Australia.
authors.forename: James G
authors.initials: JG
authors.lastname: Kench
authors.affiliation: Division of Cancer Research, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst, New South Wales, Australia. lisa.horvath@lh.org.au.|University of Sydney, Camperdown, New South Wales, Australia. lisa.horvath@lh.org.au.|Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia. lisa.horvath@lh.org.au.|Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia. lisa.horvath@lh.org.au.
authors.forename: Lisa G
authors.initials: LG
authors.lastname: Horvath
mesh_terms: D054392:Adipokines; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D002352:Carrier Proteins / Q000032:analysis*; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D008297:Male; D000072662:Margins of Excision; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000737:chemistry* / Q000473:pathology; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D016019:Survival Analysis; D000090203:Zn-Alpha-2-Glycoprotein
chemical_list: D054392:Adipokines; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D006023:Glycoproteins; C488891:AZGP1 protein, human; D000090203:Zn-Alpha-2-Glycoprotein
keywords: AZGP1; Gleason grade; localized prostate cancer; positive surgical margin; radiotherapy