Karim Chamie1, Pia Klöpfer2, Paul Bevan2, Stephan Störkel3, Jonathan Said4, Barbara Fall2, Arie S Belldegrun5, Allan J Pantuck5. 1. 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. 2. Wilex AG, Munich, Germany. 3. Institute of Pathology, University of Witten/Herdecke and HELIOS Hospital Wuppertal, Wuppertal, Germany. 4. 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. 5. 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.
Abstract
INTRODUCTION AND 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 AND MATERIALS: 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.
RCT Entities:
INTRODUCTION AND 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 AND MATERIALS: 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: Denisa L Dragu; Laura G Necula; Coralia Bleotu; Carmen C Diaconu; Mihaela Chivu-Economescu Journal: World J Stem Cells Date: 2015-10-26 Impact factor: 5.326
Authors: Ghislaine Scelo; David C Muller; Elio Riboli; Mattias Johansson; Amanda J Cross; Paolo Vineis; Konstantinos K Tsilidis; Paul Brennan; Heiner Boeing; Petra H M Peeters; Roel C H Vermeulen; Kim Overvad; H Bas Bueno-de-Mesquita; Gianluca Severi; Vittorio Perduca; Marina Kvaskoff; Antonia Trichopoulou; Carlo La Vecchia; Anna Karakatsani; Domenico Palli; Sabina Sieri; Salvatore Panico; Elisabete Weiderpass; Torkjel M Sandanger; Therese H Nøst; Antonio Agudo; J Ramón Quirós; Miguel Rodríguez-Barranco; Maria-Dolores Chirlaque; Timothy J Key; Prateek Khanna; Joseph V Bonventre; Venkata S Sabbisetti; Rupal S Bhatt Journal: Clin Cancer Res Date: 2018-07-23 Impact factor: 12.531
Authors: Karim Chamie; Nicholas M Donin; Pia Klöpfer; Paul Bevan; Barbara Fall; Olaf Wilhelm; Stephan Störkel; Jonathan Said; Michael Gambla; Robert E Hawkins; Gustavo Jankilevich; Anil Kapoor; Evgeny Kopyltsov; Michael Staehler; Kimmo Taari; Alberto J A Wainstein; Allan J Pantuck; Arie S Belldegrun Journal: JAMA Oncol Date: 2017-07-01 Impact factor: 31.777