Prostatic Neoplasms, Castration-Resistant

The supplied grounding does not support a single established cause for castration-resistant prostate neoplasms. The literature instead emphasizes treatment-emergent resistance and disease evolution under androgen deprivation therapy.

Activation of androgen receptor signaling and AR-driven transcriptional programs is central to the biology of this disease. Resistance can arise through molecular alterations in the androgen signaling axis, and some tumors evolve toward AR-indifferent states through genetic, epigenetic, and hormonal changes that promote lineage plasticity and neuroendocrine transformation. Loss of BRCA1/BRCA2-related DNA repair function and other genomic alterations are also discussed in the literature as part of the broader biology of advanced disease.

The supplied grounding does not support general population risk factors for developing castration-resistant prostate neoplasms. It does support prior exposure to androgen deprivation therapy and treatment with second-generation anti-androgens as contexts in which resistance and lineage plasticity emerge.

Treatment is generally described at the level of continued androgen deprivation therapy with sequential addition of systemic agents. The literature includes next-generation androgen receptor–directed therapies such as enzalutamide and darolutamide, androgen synthesis inhibition with abiraterone plus prednisone, taxane chemotherapy such as docetaxel, PARP inhibitors such as olaparib and rucaparib for actionable genomic alterations, immunotherapy such as pembrolizumab in selected settings, and radiopharmaceuticals such as radium-223 and lutetium-177–based therapy. Management is also guided by disease state, prior treatment, symptoms, and genomic biomarkers.