Abstract：
UNASSIGNED: The management of metastatic castrate-resistant prostate cancer (mCRPC) has evolved in the past decade due to substantial advances in understanding the genomic landscape and biology underpinning this form of prostate cancer. The implementation of various therapeutic agents has improved overall survival but despite the promising advances in therapeutic options, mCRPC remains incurable. The focus of treatment should be not only to improve survival but also to preserve the patient\'s quality of life (QoL) and ameliorate cancer-related symptoms such as pain. The choice and sequence of therapy for mCRPC patients are complex and influenced by various factors, such as side effects, disease burden, treatment history, comorbidities, patient preference and, more recently, the presence of actionable genomic alterations or biomarkers. Docetaxel is the first-line treatment for chemo-naïve patients with good performance status and those who have yet to progress on docetaxel in the castration-sensitive setting. Novel androgen agents (NHAs), such as abiraterone and enzalutamide, are effective treatment options that are utilized as second-line options. These medications can be considered upfront in frail patients or patients who are NHA naïve. Current guidelines recommend genetic testing in mCRPC for mutations in DNA repair deficiency genes to inform treatment decisions, as for example in breast cancer gene mutation testing. Other potential biomarkers being investigated include phosphatase and tensin homologues and homologous recombination repair genes. Despite a growing number of studies incorporating biomarkers in their trial designs, to date, only olaparib in the PROFOUND study and lutetium-177 in the VISION trial have improved survival. This is an unmet need, and future trials should focus on biomarker-guided treatment strategies. The advent of novel noncytotoxic agents has enhanced targeted drug delivery and improved treatment responses with favourable toxicity profiling. Trials should continue to incorporate and report health-related QoL scores and functional assessments into their trial designs.
摘要：
转移性去势抗性前列腺癌（mCRPC）的管理在过去十年中已经发展，这是由于在理解支持这种形式前列腺癌的基因组景观和生物学方面取得了实质性进展。各种治疗剂的实施改善了总体生存率，但是尽管在治疗选择方面取得了有希望的进展，mCRPC仍然无法治愈。治疗的重点不仅应该是提高生存率，而且应该是保持患者的生活质量（QoL）和改善癌症相关症状，如疼痛。mCRPC患者的选择和治疗顺序复杂，受多种因素影响，如副作用，疾病负担,治疗史,合并症,患者偏好和,最近,可操作的基因组改变或生物标志物的存在。多西他赛是化疗初治患者的一线治疗，其表现良好，而在去势敏感的情况下，多西他赛尚未取得进展。新型雄激素药物（NHAs），如阿比特龙和恩扎鲁他胺，是作为二线选项使用的有效治疗选项。这些药物可以在虚弱的患者或NHA幼稚的患者中预先考虑。目前的指南建议在mCRPC中进行DNA修复缺陷基因突变的基因检测，以指导治疗决策。例如在乳腺癌基因突变检测中。正在研究的其他潜在生物标志物包括磷酸酶和张力蛋白同源物以及同源重组修复基因。尽管越来越多的研究在他们的试验设计中加入了生物标志物，到目前为止,只有PROFOUND研究中的奥拉帕尼和VISION试验中的Luttium-177改善了生存率.这是一个未满足的需求，未来的试验应关注生物标志物指导的治疗策略.新型非细胞毒性药物的出现增强了靶向药物递送并改善了具有有利毒性的治疗反应。试验应继续将与健康相关的QoL评分和功能评估纳入其试验设计并报告。
