Prostate cancer remains the commonest cancer diagnosed in males and a leading cause of cancer-related death. Men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on chemotherapy and androgen receptor pathway inhibitors (ARPI) have limited treatment options, significant morbidity, and poor outcomes. Prostate-specific membrane antigen (PSMA)-directed radionuclide therapy (RNT) is emerging as an efficacious and well-tolerated therapy; however, disease progression is universal. Several ongoing RNT trials focus on combination strategies to improve efficacy and durability of treatment response, including combinations with ARPIs, chemotherapy, immunotherapy, and targeted therapies. Further, efforts are underway to expand the role of PSMA-directed RNT to earlier stages of disease including hormone-sensitive and localized prostate cancer. In this review, we discuss the rationale and ongoing RNT combination therapeutic trials in prostate cancer and summarize the efficacy and toxicity associated with RNT.

中文翻译：

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前列腺癌的新型放射性核素治疗组合。

前列腺癌仍然是男性中最常见的癌症，也是癌症相关死亡的主要原因。患有转移性去势抵抗性前列腺癌 (mCRPC) 且接受化疗和雄激素受体途径抑制剂 (ARPI) 治疗后病情进展的男性，治疗选择有限、发病率高且预后不佳。前列腺特异性膜抗原（PSMA）导向的放射性核素疗法（RNT）正在成为一种有效且耐受性良好的疗法；然而，疾病进展是普遍存在的。一些正在进行的 RNT 试验侧重于提高治疗反应的疗效和持久性的联合策略，包括与 ARPI、化疗、免疫疗法和靶向疗法的联合治疗。此外，人们正在努力将 PSMA 导向的 RNT 的作用扩大到疾病的早期阶段，包括激素敏感型和局限性前列腺癌。在这篇综述中，我们讨论了前列腺癌的基本原理和正在进行的 RNT 联合治疗试验，并总结了与 RNT 相关的功效和毒性。