Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma

Abstract

5112 Background: CAIX is an important molecular marker of survival and response to immunotherapy in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to prospectively evaluate the performance of CAIX in patients with metastatic RCC. Methods: This study accrued 32 consecutive patients who were treated for metastatic clear cell RCC between January 2004 and May 2006. Immunohistochemical staining of the primary tumor was performed using the mouse monoclonal antibody MN-75. Patients were stratified into two groups: high CAIX expression (>85%) and low CAIX expression (=85%) according to the percentage of cells staining positive for CAIX. Study endpoints included disease-specific survival time (DSS) and response to treatment according to RECIST criteria. Results: Four (12.5%), 21 (65.6%), and 7 patients (21.9%) were classified into low risk, intermediate risk, and high risk groups according to the University of California Integrated Staging System (UISS). Twenty (62.5%) of the 32 patients had high CAIX expression. The median follow-up was 11.4 months. Patients with low CAIX expression had significantly worse prognosis than patients with high CAIX expression (median survival: 15.2 months vs. not reached, p=0.01, 1-year DSS rate: 63% vs. 83%) and a 3.9 fold increased risk of death from RCC (95% CI, 1.2–12.7). All 4 patients in the low risk UISS group had high CAIX expression, and all were alive at 1 year. Nine patients received high dose IL-2 based immunotherapy, including 8 who had high CAIX expression, and a 1-year DSS rate of 87.5%. Of the patients expressing high CAIX, 3 (37.5%) were responders to IL-2 including 1 partial and 2 complete responses, 3 (37.5%) exhibited stable disease and 2 (25.0%) progressed during treatment. Conclusions: The results of this first prospective study of CAIX in metastatic RCC confirm that high CAIX expression is associated with better survival and enhanced response to IL-2 based immunotherapy. Patients with high CAIX expression, specifically those with low risk RCC, should be considered candidates to receive immunotherapy, whereas patients with low CAIX expression or in higher risk groups may be better candidates for targeted or other experimental therapy. No significant financial relationships to disclose.