Department of Urology, Radboud University Medical Center, Geert Grooteplein Zuid 10, 6525, GA, Nijmegen, The Netherlands.
Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Eur J Nucl Med Mol Imaging. 2021 Sep;48(10):3325-3334. doi: 10.1007/s00259-021-05283-6. Epub 2021 Mar 8.
Radium-223 is a life-prolonging therapy for castration-resistant prostate cancer (CRPC) patients with symptomatic bone metastases. However, validated biomarkers for response monitoring are lacking. The study aim was to investigate whether early alkaline phosphatase (ALP) dynamics after the first radium-223 injection can act as surrogate marker for overall survival (OS).
This retrospective multicenter study included consecutive CRPC patients treated with radium-223. Patients were divided into four subgroups based on baseline ALP level (normal/elevated) and early ALP response, defined as ≥10% ALP decrease after the first radium-223 injection. Primary endpoint was OS among the subgroups. Secondary endpoints included time to first skeletal-related event, time to ALP progression, and treatment completion rate.
A total of 180 patients were included for analysis. Median OS was 13.5 months (95% confidence interval 11.5-15.5). Patients with elevated baseline ALP without ALP response after the first injection had significantly worse OS when compared to all other patients (median OS 7.9 months versus 15.7 months, hazard ratio 2.56, 95% confidence interval 1.73-3.80, P < 0.001). Multivariate analysis demonstrated that elevated baseline ALP without ALP response after the first injection, the number of prior systemic therapies, baseline LDH level, and baseline ECOG performance status were prognostic factors of OS. Patients with elevated baseline ALP without ALP response after the first injection had significantly shorter times to ALP progression and first skeletal-related event, and more frequently discontinued radium-223 therapy when compared to other patients.
Early treatment-induced changes in ALP after one radium-223 injection were associated with OS in metastatic CRPC patients.
镭-223 是一种可延长有症状骨转移去势抵抗性前列腺癌（CRPC）患者生命的疗法。然而，目前缺乏用于监测反应的有效生物标志物。本研究旨在探讨首次镭-223 注射后碱性磷酸酶（ALP）的早期动力学是否可作为总生存期（OS）的替代标志物。
这是一项回顾性多中心研究，纳入了接受镭-223 治疗的连续 CRPC 患者。根据基线 ALP 水平（正常/升高）和早期 ALP 反应，将患者分为四组，前者定义为首次镭-223 注射后 ALP 下降≥10%，后者定义为首次镭-223 注射后 ALP 下降≥10%。主要终点是各组之间的 OS。次要终点包括首次骨骼相关事件时间、ALP 进展时间和治疗完成率。
共纳入 180 例患者进行分析。中位 OS 为 13.5 个月（95%置信区间 11.5-15.5）。与所有其他患者相比，基线 ALP 升高且首次注射后无 ALP 反应的患者 OS 显著更差（中位 OS 7.9 个月与 15.7 个月，风险比 2.56，95%置信区间 1.73-3.80，P < 0.001）。多变量分析表明，基线 ALP 升高且首次注射后无 ALP 反应、先前系统治疗的数量、基线乳酸脱氢酶（LDH）水平和基线东部肿瘤协作组（ECOG）表现状态是 OS 的预后因素。与其他患者相比，基线 ALP 升高且首次注射后无 ALP 反应的患者，ALP 进展和首次骨骼相关事件的时间更短，且更频繁地停止镭-223 治疗。
首次镭-223 注射后 ALP 的早期治疗诱导变化与转移性 CRPC 患者的 OS 相关。
