Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Prostate Cancer Translational Research Group, Barcelona, Spain.
Prostate. 2022 Aug;82 Suppl 1:S45-S59. doi: 10.1002/pros.24352.
Prostate cancer is a disease with significant interpatient genomics, with a proportion of patients presenting mutations in key homologous recombination repair (HRR) gene aberrations, particularly in late-stage disease. A better understanding of the genomic landscape of prostate cancer and the prognostic and predictive value of HRR mutations could lead to more precise care for prostate cancer patients. BRCA1/2 mutations are associated with a more aggressive disease course and higher risk of developing lethal prostate cancer, but also identify patients who could benefit from directed therapeutic strategies with PARP inhibitors. Other HRR mutations are also frequent but their prognostic and predictive value for prostate cancer patients is less clear. Moreover, a proportion of these mutations are associated with inherited germline defects, being relevant for the patients' risk of second malignancies but also to inform their relatives' risk of cancer through cascade testing. In this manuscript, we review current knowledge of the prognostic and predictive value for different HHR alterations across the different prostate cancer disease states. Additionally, we assess the challenges to implement genomic testing in clinical practice for prostate cancer patients.
前列腺癌是一种具有显著个体间基因组学差异的疾病，一部分患者表现出关键同源重组修复（HRR）基因异常的突变，特别是在晚期疾病中。更好地了解前列腺癌的基因组景观以及 HRR 突变的预后和预测价值，可以为前列腺癌患者提供更精确的治疗。BRCA1/2 突变与更具侵袭性的疾病过程和更高的致命性前列腺癌风险相关，但也确定了可以从 PARP 抑制剂等靶向治疗策略中获益的患者。其他 HRR 突变也很常见，但它们对前列腺癌患者的预后和预测价值尚不清楚。此外，这些突变中有一部分与遗传性种系缺陷相关，与患者发生第二恶性肿瘤的风险相关，也可以通过级联测试为其亲属的癌症风险提供信息。在本文中，我们回顾了不同 HRR 改变在不同前列腺癌疾病状态下的预后和预测价值的现有知识。此外，我们评估了在前列腺癌患者的临床实践中实施基因组检测所面临的挑战。
