Davis Ian D
Monash University, Level 2, 5 Arnold Street, Box Hill, Melbourne, VIC 3128, Australia.
Ther Adv Med Oncol. 2022 Mar 29;14:17588359221086827. doi: 10.1177/17588359221086827. eCollection 2022.
The mainstay of treatment for metastatic prostate cancer is androgen deprivation therapy (ADT). Outcomes with ADT are variable but control of hormone-sensitive prostate cancer (HSPC) can often be achieved for many years. Death from prostate cancer is usually due to the development of escape variants able to survive and proliferate in the setting of castrate levels of serum androgens (metastatic castration-resistant prostate cancer, mCRPC). Several agents can improve survival for patients with mCRPC, including chemotherapy, agents to reduce androgen receptor signalling, the radioisotope radium-223 dichloride, and cellular immunotherapy with sipuleucel-T. Some of these agents have been moved earlier in the disease course and have shown to improve survival in metastatic HSPC also, often to a much greater degree than when the same agents are used in mCRPC. Specifically, survival of metastatic HSPC can be improved with the addition to ADT of any one of docetaxel, abiraterone acetate/prednisone combination, apalutamide, enzalutamide, or darolutamide in combination with docetaxel. Factors affecting outcomes include the volume or burden of disease, timing of metastases relative to the original diagnosis, and patient factors determining the appropriateness of therapy. Unfortunately, uptake of this information by the clinical community remains suboptimal, with many men potentially suitable for combination therapy still receiving only ADT. Some trials have examined the effects of 'triplet' therapies although few were designed specifically to address this question. The best evidence to date suggests that triplet therapy with ADT + abiraterone + docetaxel or ADT + darolutamide + docetaxel, can improve overall survival in metastatic HSPC. Clear opportunities exist to improve survival outcomes for men with metastatic HSPC but need to be balanced against cost, accessibility, toxicity, and patient-specific factors.
转移性前列腺癌的主要治疗方法是雄激素剥夺疗法（ADT）。ADT的治疗效果因人而异，但通常可以实现对激素敏感性前列腺癌（HSPC）的多年控制。前列腺癌导致的死亡通常是由于出现了逃逸变异体，这些变异体能够在血清雄激素处于去势水平的情况下存活并增殖（转移性去势抵抗性前列腺癌，mCRPC）。有几种药物可以提高mCRPC患者的生存率，包括化疗药物、降低雄激素受体信号传导的药物、放射性同位素二氯化镭-223，以及用sipuleucel-T进行细胞免疫治疗。其中一些药物已在疾病进程中更早使用，并且已证明在转移性HSPC中也能提高生存率，通常比在mCRPC中使用相同药物时提高的程度更大。具体而言，在ADT基础上加用多西他赛、醋酸阿比特龙/泼尼松组合、阿帕他胺、恩杂鲁胺或达洛鲁胺与多西他赛联合使用中的任何一种，都可以提高转移性HSPC的生存率。影响治疗效果的因素包括疾病的体积或负担、转移时间相对于初始诊断的时间，以及决定治疗适用性的患者因素。不幸的是，临床界对这些信息的接受程度仍然不理想，许多可能适合联合治疗的男性仍仅接受ADT治疗。一些试验已经研究了“三联”疗法的效果，尽管很少有试验专门设计来解决这个问题。迄今为止的最佳证据表明，ADT + 阿比特龙 + 多西他赛或ADT + 达洛鲁胺 + 多西他赛的三联疗法可以提高转移性HSPC的总生存率。对于转移性HSPC男性患者，存在明显的机会来改善生存结果，但需要在成本、可及性、毒性和患者特定因素之间进行权衡。
