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 seven had pathologically proven NEPC (0.3%), and the median overall survival was 364 d. Three patients who underwent multi-gene panel sequencing had mutations in RB1, and 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 RB loss and DLL3 positivity. Further clinical developments targeting DLL3 are warranted.