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AKR1C3 expression in primary lesion rebiopsy at the time of metastatic castration-resistant prostate cancer is strongly associated with poor efficacy of abiraterone as a first-line therapy.

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机构: [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China [2]Department of Pathology, West China Hospital, Sichuan University, Chengdu, China [3]Department of Abdominal Oncology, West China Hospital, Sichuan University, Chengdu, China [4]Department of Ultrasound, West China Hospital, Sichuan University, Chengdu, China [5]Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China [6]Department of Urology and Comprehensive Cancer Center, University of California Davis, Sacramento, California
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关键词: abiraterone AKR1C3 docetaxel mCRPC prostate rebiopsy

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Previous studies had demonstrated that aldo-keto reductase family 1 member C3 (AKR1C3), a crucial enzyme in the steroidogenic pathway, played an important role in abiraterone (ABI)-resistance in metastatic castration-resistant prostate cancer (mCRPC) by increasing intratumoral androgen synthesis. However, its value in predicting treatment response in patients with mCRPC is unknown. Data of 163 patients with metastatic prostate cancer between 2016 and 2018 were retrospectively analyzed. All patients received androgen deprivation therapy plus bicalutamide after initial diagnosis. After mCRPC, either ABI or docetaxel (DOC) treatment was used. No patient had the experience of therapy to the primary tumor. AKR1C3 protein was detected by immunohistochemical staining from rebiopsy (re-Bx) of primary prostate lesions at mCRPC. Kaplan-Meier curves and Cox regression were used to analyze the association between AKR1C3 and treatment outcomes. AKR1C3 was positive in 58 of 163 (35.6%) cases. AKR1C3 was associated with significantly shorter median prostate-specific antigen progression-free survival (mPSA-PFS, 5.6 mo vs 10.7 mo; P < .001), median radiographic progression-free survival (mrPFS, 11.1 mo vs 18.0 mo; P = .018), and numerically shorter median overall survival (mOS, 20.4 mo vs 26.4 mo; P = .157). Notably, AKR1C3-positive patients treated with ABI, but not DOC, had shorter mPSA-PFS and mrPFS compared with AKR1C3-negative men, (mPSA-PFS, 5.7 mo vs. 11.2 mo; P < .001; mrPFS, 12.4 mo vs 23.3 mo; P = .048). However, AKR1C3 expression had no correlation to PSA response or OS. Multivariate Cox regression indicated that AKR1C3 was independently accompanied with rapid PSA progression (hazard ratio [HR], 3.64; 95% confidence interval [CI], 2.10-6.31; P < 0.001) and radiological progression (HR, 2.08; 95% CI, 1.05-4.11; P = .036) in the ABI-treated subgroup. This study demonstrated that AKR1C3 detection in tissues from prostate re-Bx at mCRPC was associated with early resistance to ABI but not DOC. These results will help to make optimal personalized treatment decisions for patients with mCRPC, facilitate physicians predicting the effectiveness of ABI. © 2019 Wiley Periodicals, Inc.

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出版当年[2019]版:
大类 | 3 区 医学
小类 | 3 区 内分泌学与代谢 3 区 泌尿学与肾脏学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 泌尿学与肾脏学 4 区 内分泌学与代谢
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第一作者机构: [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
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通讯机构: [1]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China [2]Department of Pathology, West China Hospital, Sichuan University, Chengdu, China [*1]Department of Pathology, West China Hospital, Sichuan University, 610041 Chengdu, China. [*2]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, 610041 Chengdu, China.
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