神经内分泌分化可预测阿比特龙和多西他赛作为转移性去势抵抗性前列腺癌一线治疗的疗效。

Neuroendocrine differentiation predicts the therapeutic efficacy of abiraterone and docetaxel as first-line therapy in metastatic castration-resistant prostate cancer.

机构信息

Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, China.

出版信息

J Cancer Res Clin Oncol. 2023 Aug;149(10):7247-7258. doi: 10.1007/s00432-023-04639-9. Epub 2023 Mar 13.

DOI:10.1007/s00432-023-04639-9

PMID:36907910

Abstract

PURPOSE

We aim to explore the predictive value of neuroendocrine differentiation (NED) in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving abiraterone or docetaxel as first-line therapy.

METHODS

We retrospectively analyzed data of 262 mCRPC patients receiving abiraterone or docetaxel as first-line mCRPC treatment. NED was evaluated using prostate biopsy samples at the time of mCRPC by immunohistochemical staining. Kaplan-Meier curves and Cox regression were used to assess the association between NED and treatment outcomes including PSA progression-free survival (PSA-PFS), radiographic progression-free survival (rPFS), and overall survival (OS).

RESULTS

NED was confirmed in 100/262 (38.2%) mCRPC patients, with 76/100 (76.0%) and 24/100 (24.0%) men harboring NED < 10% and NED ≥ 10%, respectively. 203/262 (77.5%) and 59/262 (22.5%) patients received abiraterone and docetaxel, respectively. In abiraterone treatment, NED was associated with a significantly shorter median PSA-PFS (mPSA-PFS, 7.5 vs. 10.3-Mo, P < 0.001), median rPFS (mrPFS, 15.9 vs. 19.5-Mo, P = 0.010), and median OS (mOS, 23.2 vs. 34.3-Mo, P = 0.014)). Likewise, for mCRPC patients receiving docetaxel, the positive detection of NED also predicted shorter mPSA-PFS (3.8 vs. 5.9-Mo, P = 0.052), mrPFS (8.4 vs. 20.4-Mo, P = 0.016) and mOS (13.6 vs. 29.0-Mo, P = 0.033). The adverse prognostic trait of NED is consistent in most subgroups. Additionally, patients' survival outcomes deteriorated as the NED proportion grew in both therapies. After propensity score matching, NED-positive patients showed comparable prognosis in abiraterone and docetaxel therapy.

CONCLUSION

For mCRPC patients receiving abiraterone or docetaxel, NED and its proportion were critical predictive factors. NED detection at mCRPC might aid in predicting patients' outcomes and optimizing treatment decisions.

摘要

目的

我们旨在探讨神经内分泌分化（NED）在接受阿比特龙或多西他赛作为一线治疗的转移性去势抵抗性前列腺癌（mCRPC）患者中的预测价值。

方法

我们回顾性分析了 262 例接受阿比特龙或多西他赛作为一线 mCRPC 治疗的 mCRPC 患者的数据。通过免疫组织化学染色，在 mCRPC 时使用前列腺活检样本评估 NED。Kaplan-Meier 曲线和 Cox 回归用于评估 NED 与治疗结局之间的关联，包括 PSA 无进展生存期（PSA-PFS）、影像学无进展生存期（rPFS）和总生存期（OS）。

结果

在 262 例 mCRPC 患者中，100/262（38.2%）例患者的 NED 得到确认，其中 76/100（76.0%）和 24/100（24.0%）例患者的 NED<10%和 NED≥10%。203/262（77.5%）和 59/262（22.5%）例患者分别接受了阿比特龙和多西他赛治疗。在阿比特龙治疗中，NED 与中位 PSA-PFS（mPSA-PFS，7.5 与 10.3 个月，P<0.001）、中位 rPFS（mrPFS，15.9 与 19.5 个月，P=0.010）和中位 OS（mOS，23.2 与 34.3 个月，P=0.014）显著缩短相关。同样，对于接受多西他赛治疗的 mCRPC 患者，NED 的阳性检测也预示着 mPSA-PFS（3.8 与 5.9 个月，P=0.052）、mrPFS（8.4 与 20.4 个月，P=0.016）和 mOS（13.6 与 29.0 个月，P=0.033）缩短。在大多数亚组中，NED 的不良预后特征是一致的。此外，随着两种治疗方法中 NED 比例的增加，患者的生存结果恶化。在倾向评分匹配后，NED 阳性患者在阿比特龙和多西他赛治疗中表现出可比的预后。