Bräuer Axel, Grubert Lena Sophie, Roll Wolfgang, Schrader Andres Jan, Schäfers Michael, Bögemann Martin, Rahbar Kambiz
Department of Nuclear Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
Department of Urology, University Hospital Münster, Münster, Germany.
Eur J Nucl Med Mol Imaging. 2017 Sep;44(10):1663-1670. doi: 10.1007/s00259-017-3751-z. Epub 2017 Jun 17.
Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with Lu-PSMA-617.
Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee.
The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1-7) of Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9-6.3 GBq). The median follow-up was 24 weeks (IQR 15-36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01).
A PSA decline after the first cycle of Lu-PSMA-617 and an initial ALP level <220 U/L were predictors of a longer OS in patients with end-stage mCRPC. An ALP level <220 U/L was additionally associated with a longer PPFS.
在过去十年中，已确立了针对前列腺特异性膜抗原（PSMA）的放射性配体疗法用于治疗转移性去势抵抗性前列腺癌（mCRPC），且显示出有前景的缓解率和良好的毒性特征。本研究的目的是评估总生存期（OS），并确定预测接受Lu-PSMA-617治疗的mCRPC患者预后的参数。
2014年12月至2017年1月期间，本研究纳入了59例连续的mCRPC患者（中位年龄72岁；四分位间距，（IQR，66 - 76岁），这些患者已接受至少一种下一代抗激素药物以及化疗。使用前列腺癌工作组3（PCWG3）标准评估生化反应。使用Kaplan-Meier估计法和Cox回归比例风险模型评估生存期。使用不良事件通用毒性标准（CTCAE）评估毒性。该研究获得了当地伦理委员会的批准。
59例患者共接受了159个周期（中位3个周期，范围1 - 7）的Lu-PSMA-617治疗（中位剂量6.11GBq，IQR 5.9 - 6.3GBq）。中位随访时间为24周（IQR 15 - 36周）。76%（45例）的患者有至少12周（PCWG3）的随访数据。对于结局结果，分析了所有接受至少一个周期治疗的患者的数据。53%的患者前列腺特异性抗原（PSA）下降≥50%，91%的患者PSA有任何程度的下降。估计中位OS为32周。初始碱性磷酸酶（ALP）水平<220 U/L以及第一个周期后PSA下降与更长的OS相关（分别为56周对28周，p < 0.01，以及56周对29周，p = 0.04）。中位估计PSA无进展生存期（PPFS）为18周。仅ALP水平<220 U/L与更长的PPFS显著相关（41周对18周，p < 0.01）。
Lu-PSMA-617第一个周期后PSA下降以及初始ALP水平<220 U/L是晚期mCRPC患者更长OS的预测指标。ALP水平<220 U/L还与更长的PPFS相关。
