Treatment Landscape of Advanced Metastatic Castration-Resistant Prostate Cancer (mCRPC)

In this Peers & Perspectives discussion, Alicia Morgans, MD, MPH, and Paul Sieber, MD, examine how the modern treatment paradigm for metastatic castration-resistant prostate cancer (mCRPC) continues to evolve with the growing role of personalized immunotherapies and precision diagnostics. The experts begin by highlighting recent advances in the therapeutic landscape, including enhanced use of germline and somatic genetic testing, microsatellite-instability status assessment, and PSMA-PET imaging, which are refining treatment decision-making. They explore how these innovations have expanded access to targeted agents and how physicians are incorporating individualized care strategies beyond guideline-defined pathways.

The discussion transitions to a deep analysis of real-world evidence supporting the use of sipuleucel-T, a personalized cellular immunotherapy for mCRPC. Morgans and Sieber evaluate new ASCO 2025 survival data, which reaffirm sipuleucel-T’s long-term benefits and durable immune response, even in patients with comorbidities or concurrent therapies. They contrast these findings with outcomes observed from enzalutamide and abiraterone acetate in real-world settings, providing balanced perspectives on efficacy, tolerability, and sequencing. The conversation highlights how patient biology, disease heterogeneity, and treatment timing can influence response durability and overall survival.

The experts conclude with a forward-looking discussion on implementation challenges and emerging innovations. They address logistical barriers to personalized immunotherapy—such as manufacturing timelines and patient coordination—and share practical strategies for streamlining integration into community practice. Finally, they look toward the future of prostate cancer immunotherapy, discussing novel agents in development and the anticipated evolution toward mechanism-based, personalized treatment models. The series underscores the importance of aligning real-world experience, diagnostic precision, and multidisciplinary collaboration to optimize outcomes in advanced prostate cancer.