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Published on: March 6, 2018
BRCA Mutation Testing in Men With Metastatic Castration-Resistant Prostate Cancer: Practical Guidance for Australian
Arun A Azad1,2, Howard Gurney3, Ainsley Campbell4
1Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
Abstract:
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.
Insights
Molecular testing for BRCA mutations in metastatic castration-resistant prostate cancer (mCRPC) is crucial for PARPi therapy. Optimizing testing practices in Australia can improve patient access to targeted treatments and outcomes.
Area of Science:
- Oncology
- Genetics
- Molecular Diagnostics
Background:
- Metastatic castration-resistant prostate cancer (mCRPC) patients may have DNA damage repair (DDR) gene defects, including BRCA1 and BRCA2.
- BRCA mutations in tumors indicate sensitivity to poly-ADP ribose polymerase inhibitors (PARPi), such as olaparib and rucaparib.
- Molecular diagnostic testing for BRCA mutations is essential for identifying eligible mCRPC patients for PARPi therapy.
Purpose of the Study:
- To provide expert recommendations for optimizing BRCA molecular diagnostic testing in mCRPC patients.
- To address practical challenges in current molecular testing pathways in Australia.
- To facilitate greater adoption of best testing practices and improve patient outcomes.
Main Methods:
- Review of current molecular diagnostic testing practices for BRCA mutations in mCRPC.
- Identification of challenges impacting testing success, including tissue handling and DNA quality.
- Development of expert recommendations for optimizing testing pathways.
Main Results:
- Current molecular testing in Australia faces challenges compromising success rates.
- Tissue handling and laboratory processing significantly impact DNA quality and sequencing data.
- Standardization of testing can enhance efficiency and patient access to PARPi.
Conclusions:
- Optimizing BRCA molecular diagnostic testing is vital for mCRPC management.
- Implementing standardized best practices can improve testing efficiency and outcomes.
- Enhanced education and awareness are key to facilitating adoption of improved testing protocols.
