Department of Radiology and Nuclear Medicine, Radboudumc, Nijmegen, the Netherlands.
Department of Urology, Radboudumc, Nijmegen, the Netherlands.
Clin Cancer Res. 2021 Jul 1;27(13):3595-3601. doi: 10.1158/1078-0432.CCR-20-4298. Epub 2021 Apr 21.
[Lu]Lu-PSMA-617 radioligand therapy (Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of Lu-PSMA in pateints with low-volume mHSPC.
Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS.
All patients received two cycles of Lu-PSMA without complications. No treatment-related grade III-IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease.
Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC.
[Lu]Lu-PSMA-617 放射性配体疗法（Lu-PSMA）是一种治疗转移性去势抵抗性前列腺癌（mCRPC）的新方法，也可应用于 PSMA 表达的转移性激素敏感性前列腺癌（mHSPC）患者。在这项前瞻性研究（NCT03828838）中，我们分析了 Lu-PSMA 在低容量 mHSPC 患者中的毒性、辐射剂量和治疗效果。
10 名接受局部治疗后的 mHSPC 进展患者，[Ga]Ga-PSMA-11 PET/诊断 CT 成像（PSMA-PET）上最多有 10 个转移病灶，且血清 PSA 倍增时间<6 个月，接受了两个周期的 Lu-PSMA 治疗。全身单光子发射 CT/CT（SPECT/CT）和血液剂量学用于计算肿瘤和危险器官（OAR）的剂量。在第 2 周期后 24 周、研究结束（EOS）时监测不良事件（AE）、实验室值（监测反应和毒性）和生活质量。所有患者在筛选时、第 1 周期后 8 周、第 2 周期后 12 周和 EOS 时进行 PSMA-PET。
所有患者均接受了两个周期的 Lu-PSMA 治疗，无并发症。未观察到与治疗相关的 III-IV 级不良事件。根据剂量学，没有任何 OAR 达到与辐射相关毒性相关的阈值剂量。此外，所有靶病灶接受的辐射剂量均高于 OAR。所有 10 名患者的 PSA 动力学均发生改变，推迟了雄激素剥夺治疗，并保持了良好的生活质量。一半的患者 PSA 反应超过 50%。一名患者在 EOS 时 PSMA-PET 成像上出现完全缓解，另外两名患者仅出现最小残留疾病。
Lu-PSMA 似乎是一种治疗低容量 mHSPC 患者的可行且安全的治疗方法。
