Epidemiology and overall survival of de novo and transformed neuroendocrine prostate cancer: a two-nation population-based study of 1,465 patients from the United States and England.

Neuroendocrine prostate cancer (NEPC) is a rare and aggressive variant of prostate cancer (PC) that can be de novo (d-NEPC) or transform from prior prostate adenocarcinoma (PCa) as treatment-emergent NEPC (t-NEPC). This study aimed to study the clinical characteristics and overall survival (OS) of NEPC using data from the SEER and NCRAS registries and to compare OS of d-NEPC and t-NEPC. A total of 1,465 patients with NEPC were extracted from SEER (n = 990, 2010-2022) and NCRAS (n = 475, 2010-2021). Patients were classified as t-NEPC if preceded by a documented PCa. The primary outcome was OS measured from the date of NEPC diagnosis. Kaplan-Meier analysis, the log-rank test, and Cox regression were performed for SEER, NCRAS, and pooled cohorts. t-NEPC represented 9.9% in NCRAS and 15.2% in SEER. Small cell carcinoma was the most common subtype (80.2% NCRAS, 74.7% SEER). Median time to transformation was 4.63 years in NCRAS and 5 years in SEER. In the pooled cohort, median OS was 9 months for d-NEPC and 7 months for t-NEPC (log-rank P < 0.001). The 60-month OS was 7.9% for d-NEPC and 4.0% for t-NEPC. In the pooled multivariable Cox regression, t-NEPC was independently associated with worse OS (aHR: 1.30, 95% CI: 1.11-1.53, P = 0.001). Data source was not associated with OS (aHR: 1.08, P = 0.206), indicating comparable OS between the USA and England. In this bi-national, population-based study, t-NEPC was associated with worse OS than d-NEPC. OS for NEPC was comparable between the USA and England. These findings support distinguishing d-NEPC from t-NEPC.