Prospective results have demonstrated favorable safety and efficacy of [¹⁷⁷Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [¹⁷⁷Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8–12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ² tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [¹⁷⁷Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [¹⁷⁷Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3–4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [¹⁷⁷Lu]Lu-PSMA is safe and has not been associated with increased grades 3–4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [¹⁷⁷Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [¹⁷⁷Lu]Lu-PSMA after a treatment break.

前瞻性结果表明，[ ¹⁷⁷ Lu]Lu-PSMA 放射性药物治疗对于患有转移性去势抵抗性前列腺癌的男性长达 6 个周期具有良好的安全性和有效性。然而，没有系统数据概述延长治疗超过 6 个周期的可行性。我们的目的是评估接受超过 6 个周期的患者延长 [ ¹⁷⁷ Lu]Lu-PSMA 放射性药物治疗的安全性和有效性。方法：本次多中心回顾性分析共纳入 111 名患者。根据个人决定，患者在 2014 年至 2023 年间接受不间断的继续治疗（连续治疗）或治疗中断后重新暴露（重新挑战治疗）。总生存期，前列腺特异性抗原 (PSA) 下降 50%（在治疗后 8-12 周测量）评估了不良事件通用术语标准的等级。应用χ ² 检验、多变量Cox回归分析和对数秩检验进行统计分析。结果：患者接受 [ ¹⁷⁷ Lu]Lu-PSMA 延长治疗，作为连续治疗 (43/111, 38.7%) 或作为重新挑战治疗 (68/111, 61.3%)，中位治疗累积剂量分别为 57.4 或 60.8 GBq。从 [ ¹⁷⁷ Lu]Lu-PSMA 治疗开始，整个队列、持续治疗组和再挑战治疗组的总生存期分别为 31.3、23.2 和 40.2 个月。复治组的初始 50% PSA 下降明显高于持续治疗组（57/63 [90.4%] vs. 26/42 [61.9%]；P = 0.006）。 62 名患者中有 23 名 (37.1%) 在第一次再挑战后观察到 PSA 下降 50%。 连续治疗和再次挑战治疗之间的 3-4 级毒性发生率相当（贫血，7/43 [16.3%] 与 13/68 [19.1%]），P = 0.6；白细胞减少症，1/43 [2.3%] vs. 2/67 [3.0%]，P = 0.3；血小板减少症，3/43 [7.0%] vs. 3/68 [4.4%]，P = 0.3；肾，2/43 [4.7%] vs. 5/68 [7.4%]，P = 0.2）。结论：[ ¹⁷⁷ Lu]Lu-PSMA 的延长治疗是安全的，并且与 3-4 级毒性增加无关。接受延长治疗的患者自第一次给药后中位生存期良好，为 31.3 个月。 [ ¹⁷⁷ Lu]Lu-PSMA 再次攻击下的反应表明，治疗中断后 [ ¹⁷⁷ Lu]Lu-PSMA 的功效得以保留。