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. 2025 Apr 1;88(4):283-289.
doi: 10.1097/JCMA.0000000000001209. Epub 2025 Jan 17.

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

Jiun-I Lai  1   2 , Yu-Ching Peng  3 , Peter Mu-Hsin Chang  1   4   5 , Yen-Hwa Chang  5   6   7 , Hsiao-Jen Chung  5   6   7 , Yi-Hsiu Huang  5   6   7 , Tzu-Ping Lin  5   6   7 , William J Huang  5   6   7 , Tzu-Chun Wei  5   6   7 , Tzu-Hao Huang  5   6   7 , Chueh-Chuan Yen  1   4   5   8
Affiliations

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

Jiun-I Lai et al. J Chin Med Assoc. .

Abstract

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.

Keywords: DLL3; Neuroendocrine; Prostate cancer.

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Conflict of interest statement

Conflicts of interest: Dr. William J. Huang, an editorial board member at the Journal of the Chinese Medical Association, had no role in the peer review process or decision to publish this article. The other authors declare no conflicts of interest related to this article’s subject matter or materials.

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