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Abstract：
Over the last two decades, there has been significant progress in the treatment of metastatic prostate cancer. Multiple treatments with diverse mechanisms of action have improved clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) including taxane chemotherapy, immunotherapy, potent androgen receptor pathway inhibitors (ARPI), and radiopharmaceuticals (radium-223). As these treatments have entered standard clinical practise, clinicians have been challenged on how to optimally select and sequence them as the landmark studies establishing their efficacy had control arms with placebo or minimally effective therapy and there is a paucity of prospective trials examining treatment sequencing. More recently, the situation has been further complicated as the earlier up-front use of docetaxel and ARPI with standard gonadal testosterone inhibition has been shown to impart substantial improvements in disease control and survival for patients with castration sensitive prostate cancer. As new therapies enter into clinical practise such as the inhibitors of Poly (ADP-Ribose) Polymerase and Prostate Specific Membrane Antigen (PSMA)-targeted therapy, how to optimally select and sequence available treatments will be a continued dilemma in the absence of validated predictive biomarkers. This review will summarize the literature supporting the use of each active agent in mCRPC. We will propose a framework which will guide the selection of appropriate agents based on prior therapies, disease characteristics and biomarkers.
摘要：
在过去的二十年里，转移性前列腺癌的治疗取得了重大进展。具有不同作用机制的多种治疗方法改善了转移性去势抵抗性前列腺癌（mCRPC）患者的临床结果，包括紫杉烷化疗。免疫疗法，强效雄激素受体途径抑制剂（ARPI），和放射性药物（镭-223）。由于这些治疗方法已经进入标准临床实践，临床医生在如何最佳选择和排序方面面临挑战,因为确立其疗效的里程碑式研究是使用安慰剂或最低限度有效治疗的对照组,并且缺乏前瞻性试验来检查治疗排序.最近,这种情况变得更加复杂,因为早期使用多西他赛和ARPI同时使用标准性腺睾酮抑制剂,已显示可显著改善去势敏感性前列腺癌患者的疾病控制和生存率.随着新疗法进入临床实践，如聚（ADP-核糖）聚合酶抑制剂和前列腺特异性膜抗原（PSMA）靶向治疗，在缺乏经过验证的预测性生物标志物的情况下,如何最佳选择和排序可用的治疗将是一个持续的难题.这篇综述将总结支持在mCRPC中使用每种活性剂的文献。我们将提出一个框架，该框架将指导基于先前疗法选择合适的药物，疾病特征和生物标志物。
