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转移性前列腺癌男性患者接受[Lu]Lu-PSMA 治疗时肿瘤标志物的价值。

The value of tumor markers in men with metastatic prostate cancer undergoing [ Lu]Lu-PSMA therapy.

机构信息

Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany.

Department of Urology, University Hospital Bonn, Bonn, Germany.

出版信息

Prostate. 2020 Jan;80(1):17-27. doi: 10.1002/pros.23912. Epub 2019 Oct 3.

Abstract

BACKGROUND

Currently, prostate-specific membrane antigen-radioligand therapy (PSMA-RLT) is considered a last-line treatment option in advanced castration-resistant prostate cancer. Despite these patients' poor prognosis, accurate estimation of their overall survival (OS) is essential to determine whether benefits exist from the treatment and whether the loss of valuable time and unnecessary side effects can be avoided. The aim of the present study is to evaluate whether various biochemical markers can predict OS in men undergoing PSMA-RLT and whether the changes assessed after PSMA-RLT correlate with the OS.

METHODS

The tested tumor markers in this retrospective analysis were alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BAP), prostate-specific antigen (PSA), lactate dehydrogenase (LDH), chromogranin A, and pro-gastrin-releasing peptide (pro-GRP). For the evaluation, we performed blood tests before each PSMA-RLT cycle and during follow-up visits (which were 2-3 months apart). All patients were followed up until their deaths. To test the correlations between the tumor markers and survival, we conducted the logrank tests and the multivariate Cox proportional-hazards regression model. The significance level was set at P < .05.

RESULTS

The study included 137 patients who received a total of 487 PSMA-RLT cycles between January 2015 and November 2017. Of the tested biochemical tumor markers, baseline ALP (120 U/L cut-off), LDH (248 U/L cut-off), and PSA (first quartile cut-off) correlated significantly with survival post-PSMA-RLT (P < .001 for ALP and LDH, and P = .007 for PSA). Stable and/or decreased values in most of the initially abnormal parameters were associated with significantly better OS; these parameters were ALP (P = .009), LDH (P = .005), PSA (P < .001), and pro-GRP (P = .013). The BAP and ALP responses also correlated significantly with survival in patients with bone metastases (P = .002 and P < .001, respectively). Furthermore, there was a strong correlation of the kinetic patterns of PSA, ALP, BAP, and LDH with the survival, showing that patients with steadily increasing markers had the shortest OS.

CONCLUSION

Along with the established tumor marker PSA, ALP, LDH, BAP, and pro-GRP were correlated with the OS post-PSMA-RLT in the univariate and multivariate analyses.

摘要

背景

目前,前列腺特异性膜抗原放射性配体治疗(PSMA-RLT)被认为是晚期去势抵抗性前列腺癌的最后一线治疗选择。尽管这些患者预后较差,但准确估计其总生存期(OS)对于确定治疗是否存在获益以及是否可以避免浪费宝贵的时间和不必要的副作用至关重要。本研究旨在评估在接受 PSMA-RLT 的男性中,各种生化标志物是否可以预测 OS,以及 PSMA-RLT 后评估的变化是否与 OS 相关。

方法

在这项回顾性分析中,我们测试了碱性磷酸酶(ALP)、骨特异性碱性磷酸酶(BAP)、前列腺特异性抗原(PSA)、乳酸脱氢酶(LDH)、嗜铬粒蛋白 A 和胃泌素释放肽前体(pro-GRP)等肿瘤标志物。为了评估,我们在每次 PSMA-RLT 周期前和随访期间(每 2-3 个月一次)进行了血液检查。所有患者均随访至死亡。为了检验肿瘤标志物与生存之间的相关性,我们进行了对数秩检验和多变量 Cox 比例风险回归模型。显著性水平设为 P<0.05。

结果

该研究纳入了 137 例于 2015 年 1 月至 2017 年 11 月期间接受 PSMA-RLT 治疗的患者,共接受了 487 个周期的治疗。在测试的生化肿瘤标志物中,基线 ALP(120 U/L 临界值)、LDH(248 U/L 临界值)和 PSA(第一个四分位数临界值)与 PSMA-RLT 后生存显著相关(ALP 和 LDH 的 P<0.001,PSA 的 P=0.007)。大多数初始异常参数的稳定和/或降低值与显著更好的 OS 相关;这些参数包括 ALP(P=0.009)、LDH(P=0.005)、PSA(P<0.001)和 pro-GRP(P=0.013)。在有骨转移的患者中,BAP 和 ALP 反应也与生存显著相关(P=0.002 和 P<0.001)。此外,PSA、ALP、BAP 和 LDH 的动力学模式与生存也具有很强的相关性,表明标志物持续增加的患者 OS 最短。

结论

除了已确立的肿瘤标志物 PSA 外,ALP、LDH、BAP 和 pro-GRP 在单变量和多变量分析中与 PSMA-RLT 后的 OS 相关。

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