尽管转移性前列腺癌的治疗最近取得了进展，但对大多数人来说，进展到去势抵抗状态仍然是不可避免的，而且预后有限。鉴于高达 25% 的病例中存在突变，建议对所有晚期前列腺癌患者进行同源重组修复途径改变的基因检测。聚（ADP-核糖）聚合酶（PARPis）现已被批准用于患有转移性去势抵抗性前列腺癌的患者，这些患者在接受雄激素受体途径抑制剂（ARPI）治疗后病情出现进展，并且具有种系或体细胞同源重组修复突变。临床前数据支持 ARPI 和 PARPi 的协同作用，因此各种 ARPI-PARPi 组合已在 III 期临床试验中进行了探索。尽管研究结果存在异质性，但明显的获益等级是显而易见的，携带 BRCA 突变的患者获得最大程度的获益，其次是任何同源重组修复突变。同源重组修复熟练队列的益处尚不清楚，并且关于是否应该向没有同源重组修复突变的患者提供 ARPI-PARPi 联合治疗的问题仍然存在。 ARPI 现在被认为是转移性激素敏感型前列腺癌的治疗标准，目前正在治疗范式的早期探索 ARPI-PARPi 联合疗法。本综述的目的是讨论 ARPI-PARPi 联合治疗背后的基本原理，总结关键临床试验的结果，并讨论临床考虑因素和未来前景。© 2024。作者。

Despite recent advances in the treatment of metastatic prostate cancer, progression to a castration-resistant state remains inevitable for most and prognosis is limited. Genetic testing for homologous recombination repair pathway alterations is recommended for all patients with advanced prostate cancer given that a mutation is present in up to 25% of cases. Poly(ADP-ribose) polymerase (PARPis) are now approved for use in patients with metastatic castration-resistant prostate cancer who have progressed on an androgen receptor pathway inhibitor (ARPI) and harbour a germline or somatic homologous recombination repair mutation. Preclinical data support a synergistic effect with an ARPI and PARPi, and various ARPI-PARPi combinations have therefore been explored in phase III clinical trials. Despite heterogeneous findings, a clear hierarchy of benefit is evident, with patients harbouring a BRCA mutation deriving the greatest magnitude of benefit, followed by any homologous recombination repair mutation. The benefit in homologous recombination repair-proficient cohort is less clear, and questions remain about whether ARPI-PARPi combination therapy should be offered to patients without a homologous recombination repair mutation. With ARPIs now considered standard-of-care for metastatic hormone-sensitive prostate cancer, ARPI-PARPi combination therapy is currently being explored earlier in the treatment paradigm. The purpose of this review is to discuss the rationale behind ARPI-PARPi combination therapy, summarise the results of key clinical trials, and discuss clinical considerations and future perspectives.© 2024. The Author(s).