Lurbinectedin in treating CNS metastases from small cell neuroendocrine prostate cancer-a case report.

De novo neuroendocrine prostate cancer is an aggressive, androgen receptor-independent subtype of prostate cancer with poor prognosis. Central nervous system (CNS) metastases from de novo neuroendocrine prostate tumors are rare, and evidence guiding treatment is limited. Lurbinectedin, approved for small cell lung cancer (SCLC), has shown activity in neuroendocrine tumors, though CNS-specific data remain sparse. A 57-year-old man presenting with tenesmus, dyschezia, and urinary retention was diagnosed with high-grade neuroendocrine prostate carcinoma with low prostate-specific antigen (PSA) and high proliferative index. Genomic profiling revealed alterations in ATM and BRCA2 and was negative for Rb1 and TP53. He achieved complete systemic response following platinum-based chemoradiotherapy and immunotherapy but later developed multifocal brain metastases with suspected leptomeningeal involvement. After progression on whole-brain radiotherapy and topotecan, lurbinectedin was initiated. Imaging demonstrated marked intracranial response, including resolution and reduction of multiple lesions. Disease progression occurred after six cycles. This case underscores similarities between neuroendocrine prostate carcinoma and SCLC, supporting the use of SCLC-based therapies. The observed response suggests that lurbinectedin may have clinically meaningful CNS activity, even after failure of standard CNS-directed treatments. Lurbinectedin may be a therapeutic option in CNS-dominant neuroendocrine prostate carcinomas. Further studies are needed to better define its intracranial efficacy and durability of response.