镥-177 PSMA 放射性配体治疗联合高剂量率近距离放疗用于先前根治性放疗后局部复发性前列腺癌：一项随机、单中心、I/II 期研究（ROADSTER）。
The use of Lutetium-177 PSMA radioligand therapy with high dose rate brachytherapy for locally recurrent prostate cancer after previous definitive radiation therapy: a randomized, single-institution, phase I/II study (ROADSTER).
机构信息
London Health Sciences Centre, London, Ontario, Canada.
Department of Oncology, Western University, London, Ontario, Canada.
出版信息
BMC Cancer. 2023 Apr 20;23(1):362. doi: 10.1186/s12885-023-10851-0.
BACKGROUND
Isolated local failure (ILF) can occur in patients who initially receive definitive radiation therapy for prostate cancer. Salvage therapy for ILF includes high dose rate (HDR) brachytherapy. Prostate Specific Membrane Antigen (PSMA) Positron Emission Tomography (PET) can accurately detect ILF and can exclude extraprostatic disease. Lutetium-177 PSMA Radioligand Therapy (RLT) is a novel treatment for prostate cancer that can target prostate cancer accurately, while sparing radiation dose to normal tissues.
METHODS
ROADSTER is a phase I/II randomized, single-institution study. Patients with an ILF of prostate cancer after definitive initial radiation therapy are eligible. The ILF will be confirmed with biopsy, magnetic resonance imaging (MRI) and PSMA PET. Patients will be randomized between HDR brachytherapy in two fractions (a standard of care salvage treatment at our institution) (cohort 1) or one treatment of intravenous Lutetium-177 PSMA RLT, followed by one fraction of HDR brachytherapy (cohort 2). The primary endpoints for the phase I portion of the study (n = 12) will be feasibility, defined as 10 or more patients completing the study protocol within 24 months of study activation; and safety, defined as zero or one patients in cohort 2 experiencing grade 3 or higher toxicity in the first 6 months post-treatment. If feasibility and safety are achieved, the study will expand to a phase II study (n = 30 total) where preliminary efficacy data will be evaluated. Secondary endpoints include changes in prostate specific antigen levels, acute toxicity, changes in quality of life, and changes in translational biomarkers. Translational endpoints will include interrogation of blood, urine, and tissue for markers of DNA damage and immune activation with each treatment.
DISCUSSION
ROADSTER explores a novel salvage therapy for ILF after primary radiotherapy with combined Lutetium-177 PSMA RLT and HDR brachytherapy. The randomized phase I/II design will provide a contemporaneous patient population treated with HDR alone to facilitate assessment of feasibility, tolerability, and biologic effects of this novel therapy.
TRIAL REGISTRATION
NCT05230251 (ClinicalTrials.gov).
背景
孤立局部失败（ILF）可发生于初始接受前列腺癌根治性放射治疗的患者中。ILF 的挽救性治疗包括高剂量率（HDR）近距离放射治疗。前列腺特异性膜抗原（PSMA）正电子发射断层扫描（PET）可准确检测 ILF 并排除前列腺外疾病。镥-177 PSMA 放射性配体治疗（RLT）是一种治疗前列腺癌的新方法，它可以准确地靶向前列腺癌，同时使正常组织免受辐射剂量的影响。
方法
ROADSTER 是一项 I/II 期随机、单机构研究。接受过根治性初始放射治疗后出现前列腺癌 ILF 的患者符合条件。ILF 将通过活检、磁共振成像（MRI）和 PSMA PET 进行确认。患者将在 HDR 近距离放射治疗两剂（我院标准的挽救性治疗）（队列 1）或单次静脉注射镥-177 PSMA RLT 治疗，随后进行 HDR 近距离放射治疗一剂（队列 2）之间进行随机分组。该研究 I 期部分（n=12）的主要终点为可行性，定义为在研究启动后 24 个月内有 10 名或更多患者完成研究方案；安全性，定义为在治疗后 6 个月内，队列 2 中无 1 名患者发生 3 级或更高级别的毒性。如果达到可行性和安全性，该研究将扩大至 II 期研究（总共 30 名患者），届时将评估初步疗效数据。次要终点包括前列腺特异性抗原水平的变化、急性毒性、生活质量的变化和转化生物标志物的变化。转化终点将包括在每次治疗时检测血液、尿液和组织中的 DNA 损伤和免疫激活标志物。
讨论
ROADSTER 探索了一种新的挽救性治疗方案，用于原发性放疗后出现的 ILF，采用联合镥-177 PSMA RLT 和 HDR 近距离放射治疗。这项 I/II 期随机设计将为接受 HDR 单独治疗的同期患者人群提供便利，有助于评估这种新疗法的可行性、耐受性和生物学效应。
试验注册
NCT05230251（ClinicalTrials.gov）。
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