Endocrine Abstracts

Background: Prostate adenocarcinoma (AC) is a very common cancer worldwide, with an estimated 54,732 new cases in the UK (2022), and approximately 313,780 in the US (2025). Prostate neuroendocrine carcinoma (NEPC) can present as De-Novo (d-NEPC) or Transformed (t-NEPC) if preceded by AC. The population incidence and prognosis of these two types is unclear, with prior studies exploring small cohorts from single centres. To address this, we studied two large population-based cancer registries, NCRAS (UK) and SEER (US), to provide robust comparative analyses of survival outcomes in d-NEPC and t-NEPC.

Methods: A total of 433 and 893 patients with NEPC were extracted from NCRAS (2012-2021) and SEER (2012-2022) databases respectively. Histology sub-types included small cell, large cell and other neuroendocrine carcinomas. Patients were classified as d-NEPC and t-NEPC. Numerical variables were presented as medians and interquartile ranges (IQR). Kaplan-Meier (KM) plots were generated to assess their overall survival (OS) with their confidence intervals (CI).

Results: The median age was 72 (IQR 66-78) and 71 (IQR 64-78) years in NCRAS and SEER respectively. t-NEPC represented 10.4% in NCRAS versus 15.9% in SEER. Small cell carcinoma was the commonest subtype (79.7% NCRAS, 74.7% SEER). Median time to transformation was 52.7 months (IQR 30.80-97.70) in NCRAS and 60 months (IQR 24.0-120.0) in SEER. In NCRAS, 60-month OS was 6.9% (CI: 4.6-10.5) and 4.4% (CI: 1.1-17.2) for d-NEPC and t-NEPC respectively. Similarly, in SEER, 60-month OS was 8% (CI: 5.9-10.7) versus 3% (CI: 0.9-9.7) for d-NEPC and t-NEPC respectively. KM plots demonstrated that t-NEPC showed worse OS than d-NEPC across both cohorts. There was no statistically significant difference in OS between histology subtypes in both cohorts.

Conclusion: This large population-based study demonstrated that transformed neuroendocrine prostate carcinoma can occur many years after prostate adenocarcinoma and is associated with significantly worse overall survival when compared to De-Novo patients. This was consistent across two independent national registries. Overall survival did not differ significantly by histological subtype. These findings emphasise the importance of considering transformation as this may change therapeutic options.