Department of Medical Oncology, Chris O'Brien Lifehouse, Camperdown.
Cancer Division, Garvan Institute of Medical Research/The Kinghorn Cancer Centre, Darlinghurst.
Ann Oncol. 2017 Aug 1;28(8):1903-1909. doi: 10.1093/annonc/mdx247.
Prostate cancers (PCs) with similar characteristics at the time of diagnosis can have very different disease outcomes. Conventional biomarkers of PC still lack precision in identifying individuals at high risk of PC recurrence. While many candidate biomarkers are proposed in the literature, few are in clinical practice as they lack rigorous validation. This study prospectively enrolled an independent phase III cohort to evaluate the clinical utility of zinc-alpha 2-glycoprotein (AZGP1) as a prognostic biomarker in localized PC.
In our multicentre, prospective phase III study, AZGP1 status in 347 radical prostatectomy specimens was assayed by immunohistochemistry in a NATA-accredited laboratory. The AZGP1 score was assessed in a multivariable model incorporating established prognostic factors. We also report extended outcomes from our previous phase II study. The primary endpoint was biochemical relapse-free survival (BRFS). Secondary endpoints were metastasis-free survival (MFS) and PC-specific survival (PCSS).
In the phase II cohort, with a median follow-up of 15.8 years, low/absent AZGP1 expression was an independent predictor of poor BRFS (HR, 1.4; 95% CI, 1.1-1.9; P = 0.03), MFS (HR, 2.8; 95% CI, 1.2-6.6; P = 0.02) and PCSS (HR, 3.8; 95% CI, 1.5-9.5; P = 0.005). These results were validated in our prospective phase III cohort. Low/absent AZGP1 expression independently predicted for BRFS (HR, 1.9; 95% CI, 1.1-3.3; P = 0.02), with shorter MFS (HR, 2.0; 95% CI, 1.1-3.4; P = 0.02). AZGP1 improved the discriminatory value when incorporated into existing prognostic risk models.
Our study provides prospective phase III validation that absent/low AZGP1 expression provides independent prognostic value in PC. This study provides robust evidence for the incorporation of this biomarker into clinical practice.
在诊断时具有相似特征的前列腺癌 (PC) 可能具有非常不同的疾病结局。传统的 PC 生物标志物在识别 PC 复发风险高的个体方面仍然缺乏准确性。虽然文献中提出了许多候选生物标志物，但由于缺乏严格的验证，它们很少在临床实践中使用。本研究前瞻性纳入了一个独立的 III 期队列，以评估锌-α 2-糖蛋白 (AZGP1) 作为局部 PC 预后生物标志物的临床实用性。
在我们的多中心、前瞻性 III 期研究中，通过免疫组织化学在 NATA 认可的实验室检测 347 例根治性前列腺切除术标本中的 AZGP1 状态。AZGP1 评分在纳入既定预后因素的多变量模型中进行评估。我们还报告了我们之前的 II 期研究的扩展结果。主要终点是生化无复发生存率 (BRFS)。次要终点是无转移生存率 (MFS) 和 PC 特异性生存率 (PCSS)。
在 II 期队列中，中位随访 15.8 年，低/无 AZGP1 表达是 BRFS（HR，1.4；95%CI，1.1-1.9；P=0.03）、MFS（HR，2.8；95%CI，1.2-6.6；P=0.02）和 PCSS（HR，3.8；95%CI，1.5-9.5；P=0.005）的独立预测因素。这些结果在我们的前瞻性 III 期队列中得到了验证。低/无 AZGP1 表达独立预测 BRFS（HR，1.9；95%CI，1.1-3.3；P=0.02），MFS 更短（HR，2.0；95%CI，1.1-3.4；P=0.02）。当纳入现有的预后风险模型时，AZGP1 提高了区分能力。
本研究提供了前瞻性 III 期验证，表明 AZGP1 缺失/低表达在 PC 中提供独立的预后价值。这项研究为将这种生物标志物纳入临床实践提供了有力的证据。
