Sequencing Strategies After Progression to mCRPC

This segment addresses treatment sequencing when patients progress from doublet therapy to metastatic castration-resistant prostate cancer (mCRPC). The discussion emphasizes avoiding ARPI-to-ARPI switches, which rarely provide durable benefit, and instead pivoting to evidence-supported options: docetaxel chemotherapy, radioligand therapy (e.g., Lu177 PSMA) for appropriate PSMA-positive disease, radium223 for symptomatic bone-predominant disease, and sipuleucel-T in eligible patients. Clinicians stressed repeat imaging and actionable testing—including updated somatic profiling—to identify candidates for PARP inhibitors or other targeted strategies, rather than changing therapy on PSA rise alone. Practical considerations include chemo fitness and willingness, drug–drug interactions, and comorbidity management. The panel also discussed oligoprogression, where limited metastatic lesions progress and can be controlled with targeted radiation while maintaining systemic therapy. Overall, the discussion emphasized biology-driven sequencing that integrates modern imaging and genomics to personalize treatment and optimize long-term outcomes.

Panelists noted that abiraterone, apalutamide, and enzalutamide demonstrate overall survival benefits, while darolutamide primarily delays progression. They discussed side-effect profiles and monitoring needs—highlighting the need for liver function monitoring and steroid co-administration with abiraterone—and emphasized that treatment selection often depends on balancing efficacy, toxicity, and clinician comfort.