Dong Baijun, Fan Liancheng, Wang Yanqing, Chi Chenfei, Ma Xiaowei, Wang Rui, Cai Wen, Shao Xiaoguang, Pan Jiahua, Zhu Yinjie, Shangguan Xun, Xin Zhixiang, Hu Jianian, Xie Shaowei, Kang Xiaonan, Zhou Lixin, Xue Wei
Department of Urology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Department of Clinical Laboratory, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Prostate. 2017 May;77(13):1373-1380. doi: 10.1002/pros.23397. Epub 2017 Aug 14.
To determine the influence of abiraterone Acetate (AA) on neuroendocrine differentiation (NED) in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC).
We conducted an analysis in 115 chemotherapy-naïve mCRPC patients who would be treated with chemotherapy. The serum levels of chromogranin A (CgA), neurone-specific enolase (NSE) were measured in 67 mCRPC patients without AA treatment and 48 patients after the failure of AA treatment, in which these markers were also measured in 34 patients before and after 6 months of AA treatment. Comparative t-test was used to evaluate the serial changes of serum NED markers during AA treatment and univariate and multivariate analyses were performed to test the influence of AA treatment on NED.
Serum CgA were NSE were evaluated to be above the upper limit of normal (ULN) in 56 (48.7%) and 29 (25.2%) patients before chemotherapy. In 34 patients with serial evaluation, serum CgA level of 14 patients and NSE of 14 patients increased after the failure of AA treatment. There was no significant difference of NED markers (CgA or NSE variation (P = 0.243) between at baseline and after the failure of AA treatment. Compared with the CgA elevation group in the first 6 months of AA treatment and baseline supranormal CgA group, the CgA decline group, and baseline normal CgA group has a much longer median PSA PFS (14.34 vs 10.00 months, P < 0.001, and 14.23 vs 10.30 months, P = 0.02) and rPFS, respectively (18.33 vs 11.37 months, P < 0.001, and 17.10 vs 12.07 months, P = 0.03). In logistic univariate analysis, AA treatment and its duration were not independent factors influencing NED.
We hypothesized that AA might not significantly lead to progression of NED of mCRPC in general. Furthermore, we found there was heterogeneity in changes of NED markers in different mCRPC patients during AA treatment. Serial CgA and NSE evaluation might help clinicians guide clinical treatment of mCRPC patients.
确定醋酸阿比特龙（AA）对未经化疗的转移性去势抵抗性前列腺癌（mCRPC）患者神经内分泌分化（NED）的影响。
我们对115例将接受化疗的未经化疗的mCRPC患者进行了分析。在67例未接受AA治疗的mCRPC患者和48例AA治疗失败后的患者中测量了嗜铬粒蛋白A（CgA）、神经元特异性烯醇化酶（NSE）的血清水平，其中还在34例患者AA治疗6个月前后测量了这些标志物。采用比较t检验评估AA治疗期间血清NED标志物的系列变化，并进行单因素和多因素分析以检验AA治疗对NED的影响。
化疗前56例（48.7%）和29例（25.2%）患者的血清CgA和NSE被评估高于正常上限（ULN）。在34例进行系列评估的患者中，AA治疗失败后14例患者的血清CgA水平和14例患者的NSE升高。AA治疗失败时与基线时NED标志物（CgA或NSE变化，P = 0.243）无显著差异。与AA治疗前6个月CgA升高组和基线CgA超正常组相比，CgA下降组和基线CgA正常组的中位PSA无进展生存期分别更长（14.34对10.00个月，P < 0.001，以及14.23对10.30个月，P = 0.0）和rPFS（18.33对11.37个月，P < 0.001，以及17.10对12.07个月，P = 0.03）。在逻辑单因素分析中，AA治疗及其持续时间不是影响NED的独立因素。
我们假设一般而言AA可能不会显著导致mCRPC的NED进展。此外，我们发现在AA治疗期间不同mCRPC患者的NED标志物变化存在异质性。连续CgA和NSE评估可能有助于临床医生指导mCRPC患者的临床治疗。
