多西紫杉醇已成为晚期前列腺癌 (PC) 护理的标准组成部分；然而，它的益处并不能为患者所普遍接受。一部分 PC 病例表现出 TMPRSS2-ERG 基因融合，导致肿瘤中 ERG 过度表达。我们的目的是评估多西紫杉醇对激素敏感 PC (HSPC) 男性疗效的生物标志物。治疗前前列腺活检是从两项随机 3 期临床试验的参与者身上获得的，该试验调查了多西紫杉醇在高危局部 PC (GETUG 12) 和转移性 HSPC 中的作用（格图 15）。对 GETUG 12 样品进行 Ki67、PTEN、RB 和磷酸化 RB 的免疫组织化学染色，对 GETUG 12 和 GETUG 15 样品进行 ERG 染色。我们使用单变量和多变量分析（根据其他经过验证的预后因素进行调整）来检查生物标志物与结果的关联。在 GETUG 12 名患者中，Ki67 与较差的无复发生存率相关（RFS；风险比 [HR] 1.72；p = 0.0092）。两项试验的汇总分析（pinteraction = 0.056）显示，基于多西他赛的化疗可改善 ERG 阳性癌症患者的无失败生存期（HR 0.58；p = 0.03），但不能改善 ERG 阴性癌症患者的无失败生存期（HR 1.08） p = 0.72）。在 GETUG 12 的 ERG 阳性亚组（高危局部 PC）中，单独使用雄激素剥夺疗法 (ADT) 时的中位 RFS 为 7.79 年，而使用 ADT 多西紫杉醇则未达到这一效果。在 ERG 阴性亚组中，单独使用 ADT 的中位无进展生存期 (mPFS) 为 7.79 年，而使用 ADT 多西他赛的中位无进展生存期 (mPFS) 为 7.08 年。在 GETUG 15（转移性 HSPC）的 ERG 阳性亚组中，单独使用 ADT 的 mPFS 为 10.7 个月，而使用 ADT 的 mPFS 为 18.8 个月。在 ERG 阴性亚组中，单独 ADT 组的 mPFS 为 10.6 个月，而 ADT 多西他赛组的 mPFS 为 13.2 个月。Ki67 可能作为 HSPC 的预后因素，而 ERG 表达似乎可以预测高风险局部和转移性 HSPC 对多西他赛的反应我们评估了可以预测晚期前列腺癌患者多西紫杉醇化疗后结果的因素。我们发现一种名为 ERG 的蛋白质的表达可以预测这些患者对多西紫杉醇的良好反应。版权所有 © 2024 欧洲泌尿外科协会。由 Elsevier B.V. 出版。保留所有权利。

Docetaxel has become a standard component of care for advanced prostate cancer (PC); however, its benefits are not universal among patients. A subset of PC cases exhibit TMPRSS2-ERG gene fusion, resulting in ERG overexpression in tumors. Our aim was to assess biomarkers for docetaxel efficacy in men with hormone-sensitive PC (HSPC).Pretreatment prostate biopsies were obtained from participants in two randomized phase 3 clinical trials investigating docetaxel in high-risk localized PC (GETUG 12) and metastatic HSPC (GETUG 15). Immunohistochemistry staining for Ki67, PTEN, RB, and phosphorylated RB was conducted for GETUG 12 samples, and ERG staining for GETUG 12 and GETUG 15 samples. We examined biomarker association with outcomes using univariate and multivariable analyses adjusted for other validated prognostic factors.Among GETUG 12 patients, Ki67 was associated with a worse relapse-free survival (RFS; hazard ratio [HR] 1.72; p = 0.0092). A pooled analysis for the two trials (pinteraction = 0.056) revealed that docetaxel-based chemotherapy improved failure-free survival for patients with ERG-positive cancer (HR 0.58; p = 0.03), but not patients with ERG-negative cancer (HR 1.08; p = 0.72). In the ERG-positive subgroup in GETUG 12 (high-risk localized PC), median RFS was 7.79 yr with androgen deprivation therapy (ADT) alone, and was not reached with ADT + docetaxel. In the ERG-negative subgroup, median progression-free survival (mPFS) was 7.79 yr with ADT alone versus 7.08 yr with ADT + docetaxel. In the ERG-positive subgroup in GETUG 15 (metastatic HSPC), mPFS was 10.7 mo with ADT alone versus 18.8 mo with ADT + docetaxel. In the ERG-negative subgroup, mPFS was 10.6 mo with ADT alone versus 13.2 mo with ADT + docetaxel.Ki67 may serve as a prognostic factor in HSPC, while ERG expression appears to predict a response to docetaxel in both high-risk localized and metastatic HSPC.We assessed factors that could predict outcomes after docetaxel chemotherapy in patients with advanced prostate cancer. We found that expression of a protein called ERG can predict a good response to docetaxel in these patients.Copyright © 2024 European Association of Urology. Published by Elsevier B.V. All rights reserved.