Schlack Katrin, Krabbe Laura-Maria, Rahbar Kambiz, Isenberg Karoline, Semjonow Axel, Schrader Andres Jan, Boegemann Martin
Department of Urology, Prostate Center, University of Muenster Medical Center, Muenster, Germany.
Department of Nuclear Medicine, University of Muenster Medical Center, Muenster, Germany.
Transl Androl Urol. 2021 Oct;10(10):3986-3999. doi: 10.21037/tau-20-1117.
In bone metastatic castration-resistant prostate cancer (bmCRPC) treated with Enzalutamide commonly used prostate-specific antigen (PSA) can be misleading since initial PSA-flares may occur. In other therapies, bouncing of alkaline phosphatase (ALP-bouncing) was shown to be a promising surrogate for survival outcome. Low lactate dehydrogenase (LDH) is usually associated with better outcome. We evaluated the prognostic ability of ALP-bouncing, LDH, PSA, and the combination of these markers after initiation of Enzalutamide.
Eighty-nine patients with bmCRPC and dynamic changes of PSA, LDH and ALP were analyzed. ALP-bouncing, an increase after therapy start followed by a decline below baseline during the first 8 weeks, LDH-normalization and PSA-decline were analyzed regarding their association with survival using Kaplan-Meier analyses and uni- and multivariate (UV and MV) Cox-regression models.
In Kaplan-Meier analysis a PSA-decline >50%, LDH-normalization and ALP-bouncing were associated with longer median progression-free survival (PFS) with 7 [95% confidence interval (CI): 4.2-9.8] 3 (2.3-3.7) months for PSA-decline (log-rank P<0.01), 6 (4.1-8) 2 (1.2-2.8) for LDH-normalization (P<0.01) and 8 (0-16.3) 3 (1.9-4.1) for ALP-bouncing (P=0.01). Analysis of overall survival (OS) showed similar, not for all parameters significant, results with 17 (11.7-22.3) 12 (7.0-17.1) months for PSA (P=0.35), 17 (13.2-20.8) 7 (5.8-8.2) for LDH-normalization (P<0.01) and 19 (7.9-30.1) 12 (7.7-16.3) for ALP-bouncing (P=0.32). In UV analysis, ALP-bouncing [hazard ratio (HR): 0.5 (0.3-1.0); P=0.02], PSA-decline >50% [HR: 0.5 (0.3-0.7); P<0.01] and LDH-normalization [HR: 0.4 (0.2-0.6); P<0.01] were significantly associated with longer PFS. For OS, LDH-normalization significantly prognosticated longer survival [HR: 0.4 (0.2-0.6); P<0.01]. In MV analysis, LDH-normalization was associated with a trend towards better OS [HR: 0.5 (0.2-1.1); P=0.09]. Comparing ALP-bouncing, LDH-normalization and PSA-decline with a PSA-decline alone, Kaplan-Meier analysis showed significantly longer PFS [11 (0.2-21.8) 4 (0-8.6); P=0.01] and OS [20 (17.7-22.3) 8 (0.3-15.7); P=0.02] in favor of the group presenting with the beneficial dynamics of all three markers. In UV analysis, the presence of favorable changes in the three markers was significantly associated with longer PFS [HR: 0.2 (0.1-0.7); P<0.01] and OS [HR: 0.3 (0.1-0.8); P=0.02].
ALP-bouncing and LDH-normalization may add to identification of bmCRPC-patients with favorable prognosis under Enzalutamide.
在用恩杂鲁胺治疗的骨转移性去势抵抗性前列腺癌（bmCRPC）中，常用的前列腺特异性抗原（PSA）可能会产生误导，因为最初可能会出现PSA升高。在其他疗法中，碱性磷酸酶波动（ALP波动）被证明是生存结果的一个有前景的替代指标。低乳酸脱氢酶（LDH）通常与较好的结果相关。我们评估了恩杂鲁胺开始治疗后ALP波动、LDH、PSA以及这些标志物组合的预后能力。
分析了89例bmCRPC患者以及PSA、LDH和ALP的动态变化。使用Kaplan-Meier分析以及单因素和多因素（UV和MV）Cox回归模型，分析了ALP波动（治疗开始后升高，随后在最初8周内降至基线以下）、LDH正常化和PSA下降与生存的相关性。
在Kaplan-Meier分析中，PSA下降>50%、LDH正常化和ALP波动与更长的中位无进展生存期（PFS）相关，PSA下降时为7[95%置信区间（CI）：4.2 - 9.8] 3（2.3 - 3.7）个月（对数秩检验P<0.01），LDH正常化时为6（4.1 - 8） 2（1.2 - 2.8）个月（P<0.01），ALP波动时为8（0 - 16.3） 3（1.9 - 4.1）个月（P = 0.01）。总生存期（OS）分析显示了类似的结果，并非所有参数都具有显著性，PSA为17（11.7 - 22.3） 12（7.0 - 17.1）个月（P = 0.35），LDH正常化为17（13.2 - 20.8） 7（5.8 - 8.2）个月（P<0.01），ALP波动为19（7.9 - 30.1） 12（7.7 - 16.3）个月（P = 0.32）。在单因素分析中，ALP波动[风险比（HR）：0.5（0.3 - 1.0）；P = 0.02]、PSA下降>50%[HR：0.5（0.3 - 0.7）；P<0.01]和LDH正常化[HR：0.4（0.2 - 0.6）；P<0.01]与更长的PFS显著相关。对于OS，LDH正常化显著预示更长的生存期[HR：0.4（0.2 - 0.6）；P<0.01]。在多因素分析中，LDH正常化与OS改善的趋势相关[HR：0.5（0.2 - 1.1）；P = 0.09]。将ALP波动、LDH正常化和PSA下降与单独的PSA下降进行比较，Kaplan-Meier分析显示，所有三个标志物呈现有益动态变化的组的PFS[11（0.2 - 21.8） 4（0 - 8.6）；P = 0.01]和OS[20（17.7 - 22.3） 8（0.3 - 15.7）；P = 0.02]显著更长。在单因素分析中，三个标志物出现有利变化与更长的PFS[HR：0.2（0.1 - 0.7）；P<0.01]和OS[HR：0.3（0.1 - 0.8）；P = 0.02]显著相关。
ALP波动和LDH正常化可能有助于识别恩杂鲁胺治疗下预后良好的bmCRPC患者。
