Azad Arun A, Gurney Howard, Campbell Ainsley, Goh Jeffrey C, Rathi Vivek
Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
Asia Pac J Clin Oncol. 2025 Aug;21(4):345-358. doi: 10.1111/ajco.14150. Epub 2025 Jan 18.
Some patients with metastatic castration-resistant prostate cancer (mCRPC) possess germline or acquired defects in the DNA damage repair (DDR) genes BRCA1 and BRCA2. Tumors with BRCA mutations exhibit sensitivity to poly-ADP ribose polymerase inhibitors (PARPi) such as olaparib and rucaparib. As a result, molecular diagnostic testing to identify patients with BRCA mutations eligible for the PARPi therapy has become an integral component of managing patients with mCRPC. There are practical challenges in the current molecular testing pathway in Australia that can compromise testing success. Testing success is often contingent on quality of tissue handling and laboratory processing techniques to minimize DNA degradation and suboptimal sequencing data quality. Greater adoption of best testing practices in Australia can be facilitated with education and greater awareness of expert recommendations. Here, we provide expert recommendations on how to optimize BRCA molecular diagnostic testing in patients with mCRPC. Optimization and standardization of molecular diagnostic testing will support health care providers and institutes in establishing more efficient testing pathways, enabling access to targeted therapies such as PARPi, and improving patient outcomes.
一些转移性去势抵抗性前列腺癌（mCRPC）患者在DNA损伤修复（DDR）基因BRCA1和BRCA2中存在种系或获得性缺陷。携带BRCA突变的肿瘤对奥拉帕利和鲁卡帕利等聚ADP核糖聚合酶抑制剂（PARPi）表现出敏感性。因此，分子诊断检测以识别符合PARPi治疗条件的BRCA突变患者已成为mCRPC患者管理的一个重要组成部分。澳大利亚目前的分子检测途径存在实际挑战，可能会影响检测的成功率。检测成功往往取决于组织处理质量和实验室处理技术，以尽量减少DNA降解和测序数据质量不佳的情况。通过教育和提高对专家建议的认识，可以促进澳大利亚更多地采用最佳检测方法。在此，我们提供关于如何优化mCRPC患者BRCA分子诊断检测的专家建议。分子诊断检测的优化和标准化将支持医疗保健提供者和机构建立更有效的检测途径，使患者能够获得PARPi等靶向治疗，并改善患者预后。
