Chamie Karim, Klöpfer Pia, Bevan Paul, Störkel Stephan, Said Jonathan, Fall Barbara, Belldegrun Arie S, Pantuck Allan J
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.
Wilex AG, Munich, Germany.
Urol Oncol. 2015 May;33(5):204.e25-33. doi: 10.1016/j.urolonc.2015.02.013. Epub 2015 Mar 29.
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.
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.
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.
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.
由于可用的预后和预测生物标志物数量有限，碳酸酐酶IX（CAIX）已成为透明细胞肾细胞癌（ccRCC）患者的重要预后生物标志物。然而，最近的研究对CAIX作为ccRCC生物标志物的作用提出了质疑。为了研究这种不确定性，我们使用ARISER研究（WX - 2007 - 03 - HR）的数据量化了CAIX与淋巴受累及生存的关联，该研究是一项涉及高危非转移性ccRCC患者的前瞻性试验。
我们回顾了ARISER研究中813例患者的记录。对组织学、分级和CAIX染色（频率和强度）进行了中心审查。CAIX评分通过将染色强度（1 - 3）乘以阳性细胞百分比（0% - 100%）得出，范围为0至300。我们使用Kaplan - Meier和多变量倾向评分调整的Cox回归分析量化了CAIX表达和评分与淋巴转移及生存（无病生存[DFS]和总生存[OS]）的关联。
该队列的中位随访时间为54.2个月。虽然56%有淋巴受累的受试者CAIX>85%，但只有33%的受试者CAIX评分≥200。在多变量分析中，CAIX>85%不是DFS和OS的统计学显著预测因子（P分别为0.06和0.15）。然而，在多变量分析中，与CAIX评分≤100相比，CAIX评分≥200与改善的DFS和OS相关（P分别为0.01和0.01）。
对高危非转移性ccRCC患者进行的最大规模、多中心、前瞻性分析表明，CAIX评分作为生存的统计学显著预后生物标志物具有实用性。我们建议对所有肾切除术后的高危疾病患者进行CAIX评分量化。
