Clonal selection of pre-existing neuroendocrine component in prostate cancer during androgen receptor signaling inhibitor therapy: A case report

Neuroendocrine prostate cancer (NEPC) is often considered treatment-induced. We report a case with pre-existing neuroendocrine differentiation that became evident during androgen receptor signaling inhibitor (ARSI) therapy. A 79-year-old man with metastatic prostate cancer received degarelix plus apalutamide. Prostate-specific antigen (PSA) decreased to <0.01 ng/mL. Subsequently, lung and liver metastases developed while PSA remained low, with neuron-specific enolase rising to 584 ng/mL. Liver biopsy revealed PSA-negative, neuroendocrine marker-positive carcinoma. Re-evaluation of initial biopsy demonstrated positivity for both PSA and neuroendocrine markers, indicating pre-existing neuroendocrine differentiation.