Targeted Therapy in mHSPC: Effects of Mutation Absence

Clinical Brief: Genetic Considerations in Treatment Planning for Recurrent Prostate Cancer

Main Discussion Topics

• Genetic Testing Recommendations: Germline testing recommended for all metastatic disease patients
• Treatment Implications: Absence of genetic alterations impacts eligibility for PARP inhibitor therapy
• Reassessment Strategy: Reevaluation for interval development of somatic mutations at disease progression
• Future Therapeutic Options: Potential role of PARP inhibitors upon castration-resistance development

Key Points for Physicians

• PARP inhibitors currently approved only for castration-resistant disease with HRR mutations
• Available PARP inhibitors include olaparib, rucaparib, talazoparib (with enzalutamide), and niraparib (with abiraterone)
• Insurance restrictions may limit somatic testing in hormone-sensitive setting
• Somatic testing at progression to castration resistance is appropriate to guide subsequent therapy

Notable Insights

The presenter emphasizes that even without current genetic alterations, reevaluation for development of somatic mutations should occur when progression to castration resistance develops.

Clinical Significance

Genetic testing is increasingly important in prostate cancer management, with results guiding both immediate treatment decisions and planning for future therapeutic interventions as disease biology evolves.