Opinion
Video
BRCA Mutations in mHSPC: Impact on Therapy Selection
Author(s):
Paul E. Dato, MD, discusses how the presence of a BRCA mutation can influence treatment selection and sequencing, supporting consideration of upfront triplet therapy intensification and planning for earlier integration of PARP inhibitors when castration resistance develops.
Clinical Brief: Genetic Considerations in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)
Main Discussion Topics
- Implications of BRCA Mutations: More aggressive molecular phenotype requiring consideration of treatment intensification
- Genetic Counseling: Recommended for all BRCA-positive patients due to implications for family members and risk of second malignancies
- Treatment Strategy Modification: Support for triplet therapy with androgen deprivation therapy, chemotherapy, and androgen receptor targeting agent
- Future Therapy Planning: Early integration of PARP inhibitors when castration resistance develops
Key Points for Physicians
- Multiple clinical trials support PARP inhibitor use in castration-resistant disease with HRR mutations:
- TALAPRO trial (talazoparib with enzalutamide)
- PROpel trial (olaparib with abiraterone)
- MAGNITUDE trial (niraparib with abiraterone)
- PROfound trial (olaparib as single agent)
- TRITON trial (rucaparib as single agent)
- Trial data should influence initial androgen receptor–targeted agent selection
- PARP inhibitors not currently indicated for hormone-sensitive disease
Notable Insights
The presence of HRR mutations warrants consideration of more aggressive upfront treatment approaches, even in borderline high-volume disease, and planning for earlier integration of PARP inhibitors upon disease progression.
Clinical Significance
Genetic testing results significantly influence both immediate treatment decisions and long-term therapeutic planning in metastatic prostate cancer management, underscoring the importance of precision medicine approaches.
