van Riel Joost H H M, Donswijk Maarten L, Brouwer Christel, Gerritsen Winald R, Tan-Phan T T Ha, Thimister Paul W L, Noordzij Walter, Te Beek Erik T, van Warmerdam Laurence J C, Bergman Andries M, van Oort Inge M, Wyndaele Dirk N J, van der Doelen Maarten J
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Nuclear Medicine, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
J Nucl Med. 2025 Jul 1;66(7):1027-1033. doi: 10.2967/jnumed.125.269746.
Ra-dichloride (Ra) is an approved therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have symptomatic bone metastases. After an initial course of 6 Ra injections, treatment may be repeated. The purpose of this study was to evaluate the safety and efficacy of Ra retreatment of mCRPC in a real-world population. This multicenter, retrospective cohort study included patients who had mCRPC and bone metastases who previously received 6 consecutive injections of Ra and received at least 1 Ra retreatment injection between 2014 and 2024. The primary endpoint was safety, measured as hematologic and nonhematologic adverse events (AEs), including skeletal-related events. Secondary endpoints included the number of injections administered, overall survival, and biochemical response rates. Exploratory analyses intended to identify variables associated with alkaline phosphatase response during retreatment, completion of Ra retreatment, and overall survival. Sixty-one patients were evaluated. Median age was 75 y, 44% of patients received prior chemotherapy, and 87% of patients previously received at least 1 androgen receptor pathway inhibitor. The median number of prior systemic therapies was 3. In total, 56 patients (95%) experienced at least 1 hematologic AE, including 14% with grade 3 hematologic AEs. Forty-four patients (72%) experienced at least 1 nonhematologic AE during Ra retreatment. No grade 4 or 5 AEs occurred. Patients received a median of 6 Ra retreatment injections. Overall survival was 16.9 mo (95% CI, 11.9-21.9 mo), and 56% of patients had an alkaline phosphatase response of at least 30%. High baseline hemoglobin levels, no prior chemotherapy, and a prostate-specific antigen response of at least 30% during the initial Ra course were predictors for completion of 6 Ra retreatment injections. A prior skeletal-related event, baseline performance status, and baseline hemoglobin level were prognostic for survival in this population. Ra retreatment was well tolerated and is therefore deemed safe in selected patients with mCRPC. In addition, the high number of administered injections and the high alkaline phosphatase response rate suggest that retreatment is beneficial to patients with advanced mCRPC. Patients with high hemoglobin levels, good performance status, and prior prostate-specific antigen response to Ra therapy may be the best candidates for Ra retreatment.
镭 - 二氯化物(Ra)是转移性去势抵抗性前列腺癌(mCRPC)且有症状性骨转移患者的一种获批治疗选择。在初始6次Ra注射疗程后,治疗可重复进行。本研究的目的是评估在真实世界人群中Ra对mCRPC进行再治疗的安全性和有效性。这项多中心回顾性队列研究纳入了患有mCRPC和骨转移且此前连续接受6次Ra注射并在2014年至2024年期间接受至少1次Ra再治疗注射的患者。主要终点是安全性,以血液学和非血液学不良事件(AE)衡量,包括骨相关事件。次要终点包括注射次数、总生存期和生化反应率。探索性分析旨在确定与再治疗期间碱性磷酸酶反应、Ra再治疗完成情况和总生存期相关的变量。对61名患者进行了评估。中位年龄为75岁,44%的患者接受过先前的化疗,87%的患者先前至少接受过1种雄激素受体途径抑制剂治疗。先前全身治疗的中位次数为3次。总共56名患者(95%)经历了至少1次血液学AE,包括14%的患者发生3级血液学AE。44名患者(72%)在Ra再治疗期间经历了至少1次非血液学AE。未发生4级或5级AE。患者接受Ra再治疗注射的中位次数为6次。总生存期为16.9个月(95%CI,11.9 - 21.9个月),56%的患者碱性磷酸酶反应至少为30%。高基线血红蛋白水平、未接受过先前化疗以及在初始Ra疗程期间前列腺特异性抗原反应至少为30%是完成6次Ra再治疗注射的预测因素。先前的骨相关事件、基线体能状态和基线血红蛋白水平是该人群生存的预后因素。Ra再治疗耐受性良好,因此在选定的mCRPC患者中被认为是安全的。此外,高注射次数和高碱性磷酸酶反应率表明再治疗对晚期mCRPC患者有益。血红蛋白水平高、体能状态良好且先前对Ra治疗有前列腺特异性抗原反应的患者可能是Ra再治疗的最佳候选人。