Genitourinary Oncology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Semin Oncol. 2013 Jun;40(3):375-92. doi: 10.1053/j.seminoncol.2013.04.008.
Effective patient care and efficient drug development require accurate tools to assess treatment effects. For metastatic castration-resistant prostate cancer (mCRPC), response biomarkers have historically been poorly reproducible, inaccurate, inconsistently applied, or only loosely associated with tangible clinical benefits such as survival. However, the field of response assessments for prostate cancer is maturing, in compliance with a rigorous process defined by analytic validation, clinical validation, and clinical qualification. For example, bone imaging with technetium-99m scintigraphy has historically been poorly used in prostate cancer clinical trials and routine patient care, and frequently has led to poor decision-making. However, contemporary clinical trial consensus criteria (Prostate Cancer Working Group 2 [PCWG2]) have standardized the definition of progression on bone scintigraphy and the clinical trials endpoint of radiographic progression-free survival (rPFS). A validated bone scan interpretation form captures the relevant data elements. rPFS and the forms have been undergoing prospective testing in multiple phase III studies. The first of these trials demonstrated a high degree of reproducibility and correlation with overall survival, and rPFS was used by the US Food and Drug Administration (FDA) for approval of abiraterone in chemotherapy-naïve mCRPC. Circulating tumor cells (CTC) are another class of assays with significant promise as response-indicator biomarkers. CTC enumeration has undergone analytic validation and has been FDA-cleared for monitoring patients with prostate cancer in conjunction with other clinical methods. It is not yet a surrogate for survival. Patient-reported outcomes (PROs) are direct indicators of patient benefit. The assays to measure PROs must undergo each of the steps of biomarker development, and are increasingly being standardized and used as clinical trial endpoints. In this review, we critically assess each of these classes of novel biomarkers--imaging, CTC, and PROs--in regard to the quality of data supporting their use to monitor clinical outcomes in advanced prostate cancer.
有效的患者护理和高效的药物开发需要准确的工具来评估治疗效果。对于转移性去势抵抗性前列腺癌（mCRPC），反应生物标志物在历史上一直是可重复性差、不准确、应用不一致，或者仅与生存等实际临床益处松散相关。然而，前列腺癌反应评估领域正在成熟，符合由分析验证、临床验证和临床资格定义的严格流程。例如，锝-99m 闪烁扫描术在前列腺癌临床试验和常规患者护理中的应用一直很差，并且经常导致决策不佳。然而，当代临床试验共识标准（前列腺癌工作组 2 [PCWG2]）已经标准化了骨扫描进展的定义和放射学无进展生存期（rPFS）的临床试验终点。经过验证的骨扫描解释表格捕获了相关的数据元素。rPFS 和表格正在多项 III 期研究中进行前瞻性测试。其中第一项试验证明了高度的可重复性和与总生存期的相关性，rPFS 被美国食品和药物管理局（FDA）用于批准阿比特龙在化疗初治 mCRPC 中的应用。循环肿瘤细胞（CTC）是另一类具有很大潜力的反应标志物。CTC 计数已经经过了分析验证，并已获得 FDA 批准，可与其他临床方法一起监测前列腺癌患者。它尚未成为生存的替代品。患者报告的结果（PROs）是患者受益的直接指标。用于测量 PROs 的检测方法必须经过生物标志物开发的每个步骤，并且越来越标准化并用作临床试验终点。在这篇综述中，我们批判性地评估了这些新型生物标志物的每一类——成像、CTC 和 PROs——就其用于监测晚期前列腺癌临床结果的数据质量。
