CRPC

Castration-resistant prostate cancer (CRPC) is prostate cancer that continues to progress despite castration-level testosterone, defined as less than 50 ng/dL, achieved by surgical castration or ongoing androgen-deprivation therapy. CRPC may develop after treatment of hormone-sensitive disease or present as metastatic disease that remains active despite castration.

The cancer often remains driven by androgen receptor signaling even at low testosterone. Mechanisms include AR gene amplification or mutation, intratumoral androgen synthesis, splice variants, and activation of alternative growth pathways or neuroendocrine differentiation. CRPC is diagnosed when progression occurs despite castration, evidenced by rising PSA, new or enlarging lesions on imaging, or worsening symptoms, with testosterone below 50 ng/dL.

Treatment aims to slow progression and relieve symptoms, and may extend survival. Options include androgen receptor pathway inhibitors (abiraterone acetate, enzalutamide, apalutamide); chemotherapy (docetaxel, cabazitaxel); radiopharmaceuticals (radium-223 for symptomatic bone metastases); PARP inhibitors for tumors with BRCA1/2 or other homologous recombination repair mutations; Lutetium-177-PSMA-617 for PSMA-positive disease after prior therapy; sipuleucel-T for asymptomatic or minimally symptomatic metastatic CRPC; and bone-targeted agents to reduce skeletal events.

Prognosis is variable and depends on disease extent and molecular features; however, newer treatments have improved survival for many patients. Monitoring typically includes prostate-specific antigen levels, periodic imaging, and assessment of symptoms, with sustained suppression of testosterone below castration levels. Ongoing research continues to explore combination strategies, sequencing, and biomarker-driven approaches.