同步转移的去势敏感型前列腺癌（mCSPC）的标准治疗方案包括雄激素剥夺疗法与第二代抗雄激素疗法和/或多西他赛。最近的随机数据显示，前列腺定向治疗（PDT）与低体积转移性疾病患者的总体生存率（OS）有所改善。肿瘤基因组学代表了定义mCSPC患者临床进程的附加维度。为了评估高风险（HiRi）基因组标志对PDT效益的预测作用，我们对接受了肿瘤DNA面板测序的同步低体积mCSPC男性进行了一项单中心回顾性研究。根据是否存在HiRi突变，包括TP53、ATM、BRCA1、BRCA2或Rb1的致病性突变，对患者进行了分类。主要终点是确定HiRi突变对PDT对OS的影响。采用Kaplan-Meier方法进行生存分析，并与log-rank检验和多变量Cox回归进行比较。评估HiRi突变与PDT之间的相互作用。共纳入了101例同步低体积CSPC患者，随访中位数为44个月。约有一半的患者被发现具有HiRi致病性突变（49%）。具有HiRi突变的患者，无PDT组与PDT组的中位OS分别为73个月与66.8个月（p=0.3）。相反，没有HiRi突变的患者，无PDT组与PDT组的中位OS分别为60个月与105.3个月（p<0.001）。对于PDT与HiRi突变之间的OS相互作用，p值在统计学上是显著的（p<0.001）。研究的局限性包括回顾性的性质。在这里，我们确定了一种HiRi基因组标志物，似乎可以预测同步低体积mCSPC患者对PDT的效益不明显。进一步验证这些结果的工作是必要的。在该报告中，我们评估了一种高风险基因组生物标志物，用于预测同步低体积转移性去势敏感型前列腺癌男性患者接受前列腺定向治疗的效益。我们发现，没有高风险突变的男性患者似乎比具有高风险突变的男性患者更能从前列腺定向治疗中获得临床益处。© 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Standard of care management for synchronous metastatic castration-sensitive prostate cancer (mCSPC) includes androgen deprivation therapy with a second-generation antiandrogen therapy and/or docetaxel. Recently, randomized data have demonstrated that prostate-directed therapy (PDT) is associated with an improvement in overall survival (OS) among patients with low-volume metastatic disease. Tumor genomics represents an additional dimension to define the clinical trajectory of patients with mCSPC.To evaluate a high-risk (HiRi) genomic signature to predict the benefit from PDT.We performed a single-institution retrospective review of men with synchronous low-volume mCSPC who underwent DNA panel sequencing of their tumor. Patients were classified according to the presence of HiRi mutation including pathogenic mutations in TP53, ATM, BRCA1, BRCA2, or Rb1.The primary endpoint was to determine the effect of PDT on OS in patients with and without a HiRi mutation. A survival analysis was performed with the Kaplan-Meier method compared with log-rank test and multivariable Cox regression. The interaction between HiRi mutation and PDT was evaluated.A total of 101 patients with synchronous low-volume CSPC were included with a median follow-up of 44 mo. Approximately half of patients were found to have a HiRi pathogenic mutation (49%). Patients with HiRi mutations demonstrated median OS of 73 versus 66.8 mo (p = 0.3) for no PDT versus PDT. Conversely, patients without a HiRi mutation demonstrated a significant improvement in OS of 60 versus 105.3 mo (p < 0.001) for no PDT versus PDT. The p value for interaction for OS between PDT and HiRi mutation was statistically significant (p < 0.001). Limitations include the retrospective nature of the study.Here, we have identified a HiRi genomic biomarker that appears predictive for the lack of benefit from PDT in men with synchronous low-volume mCSPC. Further work validating these results is warranted.In this report, we evaluated a high-risk genomic biomarker to predict the benefit from prostate-directed therapy for men with synchronous low-volume metastatic castration-sensitive prostate cancer. We found that men without a high-risk mutation appear to experience a greater clinical benefit from prostate-directed therapy than those with a high-risk mutation.Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.