Diagnostic Challenge in Treatment-Emergent Neuroendocrine Prostate Cancer: A Case Requiring Prostate Rebiopsy After...

Treatment-emergent neuroendocrine prostate cancer (t-NEPC) is an aggressive variant arising from lineage plasticity after androgen receptor pathway inhibitor therapy. We report an 80-year-old man with metastatic prostate adenocarcinoma treated with enzalutamide who developed lung lesions despite stable prostate-specific androgen levels. A transbronchial lung biopsy revealed poorly differentiated carcinoma without confirmation of the primary site. Suspecting t-NEPC based on his treatment history, a prostate rebiopsy confirmed the diagnosis. He was treated with carboplatin, etoposide, and durvalumab, but he later succumbed to carcinomatous meningitis. This case highlights the limitations of small metastatic biopsies and the importance of considering phenotypic transformation during prostate cancer treatment.