A narrative review of advances in biomarker guided multidisciplinary systemic therapy for metastatic castration resistant prostate cancer

Prostate cancer management increasingly requires multidisciplinary coordination across urology, medical oncology, radiation oncology, nuclear medicine, radiology, pathology, and genetics, particularly after progression to advanced disease states. Although androgen deprivation therapy remains effective in hormone-sensitive disease, many patients ultimately develop castration-resistant prostate cancer, and metastatic castration-resistant prostate cancer remains a major lethal stage. Over the past two decades, systemic treatment has evolved from taxane-centered therapy to a biomarker-guided framework comprising six established classes: androgen receptor pathway inhibitors, taxane chemotherapy, poly(ADP-ribose) polymerase inhibitors, prostate-specific membrane antigen radioligand therapy, bone-targeted radium-223, and immunotherapy. This narrative review critically appraises the biological rationale, pivotal clinical evidence, study populations, limitations, toxicities, and practical implications of these approaches. Particular attention is given to androgen receptor pathway inhibitor cross-resistance, heterogeneous benefit among homologous recombination repair genes, negative phase III immunotherapy trials, the timing of prostate-specific membrane antigen radioligand therapy, and sequencing after first-line intensification or androgen receptor pathway inhibitor–PARP inhibitor combinations. Optimal sequencing remains unresolved; homologous recombination repair alterations should not be treated as equivalent, and genomic and imaging findings must be interpreted alongside prior therapy, disease tempo and distribution, symptoms, fitness, access, and patient preferences within multidisciplinary care.