Real-world experience in treatment outcome and genomic insights for metastatic prostate neuroendocrine carcinoma

Background: Neuroendocrine prostate cancer (NEPC) (de novo or treatment-related [t-NEPC]) is a rare and deadly variant of prostate cancer. While de novo NEPC is rare, t-NEPC occurs more frequently in patients with castration-refractory prostate cancer. Owing to the rarity of NEPC, no standard treatment has been established, and the outcomes are generally unsatisfactory. Methods: This study retrospectively reviewed NEPC cases at Taipei Veterans General Hospital between 2018 and 2023. Clinical outcomes, treatment modalities, and related genomic profiles were recorded. We also performed a literature review of case series reporting the outcomes of chemotherapeutic regimens for NEPC. Results: From 2158 cases of prostate cancer cases diagnosed during the study period, only 7 had pathologically proven NEPC (0.3%), and the median overall survival was 364 days. Three patients who underwent multigene panel sequencing had mutations in RB1, and delta-like ligand 3 (DLL3) immunohistochemical staining showed a positivity rate of 50%. We performed a literature review on chemotherapy outcomes in patients with NEPC. In six studies with 104 patients, etoposide + platinum treatment was most commonly used. The progression-free survival (PFS) and overall survival ranged from 3.4 to 9.3 and 8.4 to 22.4 months, respectively. The response rates ranged from 44% to 69.2%. These studies were consistent with a dismal overall survival rate, despite a high response rate to the initial chemotherapy regimen. Conclusion: Our study reported poor outcomes with chemotherapy, with a high frequency of retinoblastoma protein (RB) loss and DLL3 positivity. Further clinical developments targeting DLL3 are warranted.