Metastatic prostate cancer is associated with considerable morbidity and mortality. Standard treatment for non-metastatic prostate cancer, to prevent metastatic progression, is androgen deprivation therapy (ADT); however, many patients will eventually develop castration-resistant prostate cancer (CRPC), which can prove challenging to treat. Between the stages of non-metastatic androgen-sensitive disease and metastatic CRPC is an intermediate disease state that has been termed non-metastatic CRPC (nmCRPC), which is a heterogeneous, man-made disease stage that occurs after a patient who has no radiological evidence of metastasis shows evidence of cancer progression even after ADT. Awareness of nmCRPC has risen owing to an increased use of ADT and its eventual failure. Men with nmCRPC are at a high risk of progression to mCRPC, with historically few options to halt this process. However, in the past two decades, multiple therapies have been investigated for the treatment of nmCRPC, including endothelin receptor antagonists and bone-targeted therapies, but none has changed the standard of care. In the past decade, the efficacy of androgen receptor pathway-targeting modalities has been investigated. Three novel nonsteroidal antiandrogen agents for treating high-risk nmCRPC have been investigated; the PROSPER, SPARTAN and ARAMIS trials were phase III, randomized, placebo-controlled clinical trials that investigated the efficacy and safety of enzalutamide, apalutamide and darolutamide, respectively. All three therapeutics showed statistically significant improvements in metastasis-free survival, progression to antineoplastic therapy was lengthened and at final analysis, overall survival was significantly improved. The comparative efficacy and safety of all three agents has not yet been investigated in a comprehensive clinical trial, but approval of these medications by the FDA and other regulatory agencies means that providers now have three effective therapeutic options to augment ADT for patients with nmCRPC.

转移性前列腺癌与相当大的发病率和死亡率有关。为防止转移进展，非转移性前列腺癌的标准治疗是雄激素剥夺疗法 (ADT)；然而，许多患者最终会发展为去势抵抗性前列腺癌 (CRPC)，这可能证明治疗具有挑战性。在非转移性雄激素敏感疾病和转移性 CRPC 的阶段之间是一种中间疾病状态，被称为非转移性 CRPC (nmCRPC)，这是一种异质的、人为的疾病阶段，发生在没有放射学检查的患者之后转移的证据显示即使在 ADT 后癌症进展的证据。由于 ADT 使用的增加及其最终失败，人们对 nmCRPC 的认识有所提高。患有 nmCRPC 的男性进展为 mCRPC 的风险很高，历史上很少有选择来停止这个过程。然而，在过去二十年中，已经研究了多种治疗 nmCRPC 的疗法，包括内皮素受体拮抗剂和骨靶向疗法，但没有一种疗法改变了护理标准。在过去的十年中，已经研究了雄激素受体通路靶向方式的功效。已经研究了三种用于治疗高危 nmCRPC 的新型非甾体抗雄激素药物；PROSPER、SPARTAN 和 ARAMIS 试验是 III 期随机安慰剂对照临床试验，分别研究了恩杂鲁胺、阿帕鲁胺和达洛鲁胺的疗效和安全性。所有三种疗法均显示无转移生存期有统计学意义的显着改善，延长了抗肿瘤治疗的进展，并且在最终分析中，总体生存率显着提高。尚未在综合临床试验中研究所有三种药物的疗效和安全性，但 FDA 和其他监管机构批准这些药物意味着提供者现在有三种有效的治疗选择来增加 nmCRPC 患者的 ADT。