Treatment Selection Considerations in mCRPC
An expert explains that metastatic castration-resistant prostate cancer (mCRPC) treatment is guided by prior therapies, disease features, and genetic profiles—favoring androgen receptor pathway inhibitors (ARPIs) for those without progression, PARP inhibitor combinations for patients with BRCA-mutated disease, and tailored options such as radium-223 for bone metastases or chemotherapy for aggressive, genetically altered tumors—with evolving strategies including radioligand therapies aimed at improving survival while preserving quality of life.
Treatment of metastatic castration-resistant prostate cancer (mCRPC) mCRPC depends heavily on prior therapies, disease characteristics, and genetic profiles. For patients who have not progressed on androgen receptor pathway inhibitors (ARPIs)ARPIs, reusing agents such as enzalutamide or abiraterone remains a common approach. Genomic profiling plays a critical role in guiding treatment, especially for those harboring BRCA1 or BRCA2 mutations. In these patients, combination therapies involving PARP inhibitors plus ARPIs have shown promising efficacy. For patients with other homologous recombination repair (HRR) mutations, similar combination regimens may be offered. Treatment choices are also influenced by symptom burden and disease progression rate, with less aggressive disease managed differently than rapidly progressing cases.
In patients with mildly symptomatic bone metastases and no HRR mutations, combining ARPIs with radiopharmaceutical agents like such as radium-223 offers a well-tolerated treatment option that balances efficacy with quality of life. Conversely, those exhibiting aggressive disease features—particularly with genetic alterations such as RB1, PTEN, or TP53 loss—may benefit from initiating chemotherapy with agents like such as docetaxel upfront, addressing the high tumor burden more effectively. This tailored approach reflects a shift toward personalized care, optimizing outcomes based on individual tumor biology and patient condition.
For patients who have progressed after ARPI therapy, overall survival tends to be shorter, necessitating alternative strategies. Chemotherapy with docetaxel is a standard option, and cabazitaxel is typically used in those previously treated with docetaxel in earlier disease stages. In cases of high-volume visceral metastases, combining cabazitaxel with carboplatin may induce rapid tumor shrinkage. Additionally, newer treatments such as PSMA prostate-specific membrane antigen-targeted radioligand therapies are emerging, offering hope for improved outcomes. Treatment duration and endpointend points focus not only on extending survival but also on maintaining quality of life and minimizing treatment-related toxicity.
