对于最初对 PSMA-RLT 有反应并经历部分缓解但在缓解一定时间后复发进展的患者，建议重新接受 [177Lu]Lu-PSMA-617 放射配体治疗 (RLT)。然而，关于这种方法的数据有限。在这项研究中，我们分析了来自前瞻性登记（REALITY 研究，NCT04833517）的患者在最初从 PSMA-RLT 中受益后，进行一系列或多组 [177Lu]Lu-PSMA-617 RLT 的疗效和安全性。七名转移性去势抵抗性前列腺癌 (mCRPC) 患者对初始 [177Lu]Lu-PSMA-617 RLT 有生化反应，随后疾病进展，接受了至少一个（最多三个）系列的 [177Lu]Lu-PSMA-617 RLT 重新挑战。计算基于前列腺特异性抗原（PSA）血清值、基于PSA的无进展生存期（PFS）和总生存期（OS）的生化反应率。治疗的不良事件根据“不良事件通用术语标准”(CTCAE) 进行评估。在一系列 RLT 重新挑战后，27/47 名患者 (57.4%) 的 PSA 下降了至少 50%。所有患者的中位 PFS 为 8.7 个月，中位 OS 为 22.7 个月，均根据第一次再挑战系列的给药计算。对再次挑战有反应（PSA 下降≥50%）的患者的中位 OS 为 27.3 个月。关于 PFS，在这些患者中发现比较初始 RLT 和再挑战 RLT 之间存在显着相关性（r = 0.4128，p = 0.0323）。 10 名患者接受了第二次再挑战系列，3 名患者接受了第三次再挑战系列，其中 8/10 和 3/3 的患者对重复 RLT 再次挑战有反应。未观察到按 CTCAE 标准评定的不良事件的严重恶化。[177Lu]Lu-PSMA-617 RLT 再挑战与显着的 PSA 反应和令人鼓舞的生存结果以及非常有利的安全性相关，因此应被视为直接治疗为先前受益于 PSMA-RLT 的 mCRPC 患者提供前瞻性治疗选择。© 2024。作者。

Rechallenge of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) was proposed for patients who initially responded to PSMA-RLT experiencing partial remission, but relapsed into progression after a certain period of remission. However, only limited data is available regarding this approach. In this study, we analyzed the efficacy and safety profile of one or more series of [177Lu]Lu-PSMA-617 RLT rechallenge in patients from a prospective registry (REALITY Study, NCT04833517) after they initially benefited from PSMA-RLT.Forty-seven patients with metastatic castration-resistant prostate cancer (mCRPC) who had biochemical response to initial [177Lu]Lu-PSMA-617 RLT followed by disease progression received at least one (up to three) series of [177Lu]Lu-PSMA-617 RLT rechallenge. Biochemical response rates based on prostate-specific antigen (PSA) serum value, PSA-based progression-free survival (PFS) and overall survival (OS) were calculated. Adverse events of the treatment were assessed according to 'common terminology criteria for adverse events' (CTCAE).After one series of RLT rechallenge, a PSA decline of at least 50% was achieved in 27/47 patients (57.4%). The median PFS of all patients was 8.7 mo and the median OS was 22.7 mo, each calculated from the administration of the first rechallenge series. Patients who responded (PSA decline > 50%) to the rechallenge showed a median OS of 27.3 mo. Regarding PFS, a significant correlation (r = 0.4128, p = 0.0323) was found for these patients comparing initial and rechallenge RLT. Ten patients received a second and 3 patients received a third rechallenge series with 8/10 and 3/3 patients responding to repeated RLT rechallenge. No severe deterioration of adverse events rated by CTCAE criteria was observed.[177Lu]Lu-PSMA-617 RLT rechallenge is associated with significant PSA response and encouraging survival outcome as well as a very favourable safety profile and should therefore be considered as a straight-forward treatment option in mCRPC patients, who previously benefited from PSMA-RLT.© 2024. The Author(s).