患有高危前列腺癌 (PCa) 的男性接受雄激素剥夺疗法 (ADT) 和放射疗法治疗，但 30% 的患者会复发。 PCa治疗后的生化复发受肿瘤缺氧的影响。高度缺氧的肿瘤具有侵袭性、对治疗有抵抗力并且转移能力增加。来自诊断活检的基因表达特征可以预测肿瘤缺氧和放射敏感性，但由于担心这些生物标志物对新患者群体的适用性，没有一个在常规临床中使用。在高风险 PCa 队列中没有进行或有限的测试。我们为高风险 PCa 患者队列生成了转录组数据。患者接受 ADT 治疗，然后接受外照射放射治疗，有或没有近距离放射治疗。从文献中筛选的生物标志物是根据治疗前活检基因表达数据计算的。生存分析的主要终点是生化无复发生存 (bRFS)，次要终点是无远处转移生存 (DMFS) 和总生存。所选生物标志物的性能较差，没有一个对 bRFS 或 DMFS 具有预后意义在任何队列中。近距离放射治疗加强队列比传统分割或大分割队列接受的 ADT 持续时间更短（Wilcoxon 秩和检验，p 分别为 2.1×10-18 和 2.3×10-10），并且远处转移的风险增加（对数秩检验， p=8×10-4）。生物标志物评分与任何终点的结果之间都没有一致的关系。缺氧和放射敏感性生物标志物对于接受 ADT 加放疗治疗的高危 PCa 患者并不能预测预后。我们推测，缺乏预后能力可能是由于这些高危患者在放疗之前和期间接受的 ADT 的不同缺氧调节作用所致。在推荐缺氧生物标志物用于治疗前的常规临床使用之前，需要更深入地了解与患者特征、样本处理和治疗方式相关的生物标志物结构、性能和队列间可转移性。版权所有 © 2024。由 Elsevier 出版公司

Men with high-risk prostate cancer (PCa) are treated with androgen deprivation therapy (ADT) and radiotherapy, but the disease reoccurs in 30% of patients. Biochemical recurrence of PCa after treatment is influenced by tumour hypoxia. Tumours with high levels of hypoxia are aggressive, resistant to treatment, and have increased metastatic capacity. Gene expression signatures derived from diagnostic biopsies can predict tumour hypoxia and radiosensitivity, but none are in routine clinical use, due to concerns about the applicability of these biomarkers to new patient cohorts. There has been no or limited testing in cohorts of high-risk PCa.We generated transcriptomic data for cohorts of high-risk PCa patients. Patients were treated with ADT followed by external beam radiotherapy with or without a brachytherapy boost. Biomarkers curated from the literature were calculated from pre-treatment biopsy gene expression data. The primary endpoint for survival analyses was biochemical recurrence-free survival (bRFS) and the secondary endpoints were distant metastasis-free survival (DMFS) and overall survival.The performance of the selected biomarkers was poor, with none achieving prognostic significance for bRFS or DMFS in any cohort. The brachytherapy boost cohort received shorter durations of ADT than the conventionally fractionated or hypofractionated cohorts (Wilcoxon rank sum test, p=2.1 × 10-18 and 2.3 × 10-10 respectively) and had increased risk of distant metastasis (log-rank test, p=8 × 10-4). There were no consistent relationships between biomarker score and outcome for any of the endpoints.Hypoxia and radiosensitivity biomarkers were not prognostic in high-risk PCa patients treated with ADT plus radiotherapy. We speculate that the lack of prognostic capability could be caused by the variable hypoxia-modifying effects of the ADT that these high-risk patients received before and during definitive treatment with radiotherapy. A deeper understanding of biomarker construction, performance and inter-cohort transferability in relation to patient characteristics, sample handling and treatment modalities is required before hypoxia biomarkers can be recommended for routine clinical use in the pre-treatment setting.Copyright © 2024. Published by Elsevier Inc.