title: Carbonic anhydrase-IX score is a novel biomarker that predicts recurrence and survival for high-risk, nonmetastatic renal cell carcinoma: Data from the phase III ARISER clinical trial.
abstract: OBJECTIVE
  With a limited number of prognostic and predictive biomarkers available, carbonic anhydrase-IX (CAIX) has served as an important prognostic biomarker for patients with clear cell renal cell carcinoma (ccRCC). However, studies have recently called into question the role of CAIX as a biomarker for ccRCC. To investigate this uncertainty, we quantified the association of CAIX with lymphatic involvement and survival using data from ARISER study (WX-2007-03-HR)--a prospective trial involving subjects with high-risk nonmetastatic ccRCC.
  
  
  METHODS
  We reviewed the records of 813 patients enrolled in the ARISER study. Central review of histology, grade, and CAIX staining (frequency and intensity) was performed. CAIX score was derived by multiplying the staining intensity (1-3) by percent positive cells (0%-100%), yielding a range of 0 to 300. We quantified the association of CAIX expression and score with lymphatic spread and survival (disease-free survival [DFS] and overall survival [OS]) using Kaplan-Meier and multivariable propensity score adjusted Cox regression analyses.
  
  
  RESULTS
  Median follow-up of the cohort was 54.2 months. Although 56% of subjects with lymphatic involvement had CAIX>85%, only 33% had CAIX score ≥ 200. On multivariable analysis, CAIX>85% was not a statistically significant predictor of DFS and OS (P = 0.06 and P = 0.15, respectively). However, CAIX score ≥ 200, when compared with CAIX score ≤ 100, was associated with improved DFS and OS (P = 0.01 and P = 0.01, respectively) on multivariable analysis.
  
  
  CONCLUSIONS
  The largest, multicenter, prospective analysis of patients with high-risk nonmetastatic ccRCC demonstrates the utility of CAIX score as a statistically significant prognostic biomarker for survival. We recommend that CAIX score be quantified for all patients with high-risk disease after nephrectomy.
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA; Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Electronic address: kchamie@mednet.ucla.edu.
authors.forename: Karim
authors.initials: K
authors.lastname: Chamie
authors.affiliation: Wilex AG, Munich, Germany.
authors.forename: Pia
authors.initials: P
authors.lastname: Klöpfer
authors.affiliation: Wilex AG, Munich, Germany.
authors.forename: Paul
authors.initials: P
authors.lastname: Bevan
authors.affiliation: Institute of Pathology, University of Witten/Herdecke and HELIOS Hospital Wuppertal, Wuppertal, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Störkel
authors.affiliation: Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA; Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA; Department of Pathology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Said
authors.affiliation: Wilex AG, Munich, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Fall
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA; Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: Arie S
authors.initials: AS
authors.lastname: Belldegrun
authors.affiliation: Department of Urology, David Geffen School of Medicine at UCLA, Los Angeles, CA; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA; Institute of Urologic Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA.
authors.forename: Allan J
authors.initials: AJ
authors.lastname: Pantuck
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002256:Carbonic Anhydrases / Q000096:biosynthesis / Q000378:metabolism*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D011446:Prospective Studies
chemical_list: D014408:Biomarkers, Tumor; D002256:Carbonic Anhydrases
keywords: Adjuvant therapy; CAIX; Clinical trial; Prognostic biomarker; Renal cell carcinoma