Potential risk factors, course of disease, and clinical outcomes of neuroendocrine prostate cancer (NEPC): A retrospective analysis.

e17051 Background: Despite the rising number of newly diagnosed neuroendocrine prostate cancer (NEPC), there is little data available on risk factors and the course of disease. Methods: Patients (pts) with NEPC who were treated at the University Medical Center Hamburg-Eppendorf Germany between 05/2018 and 10/2024 were retrospectively analyzed. Descriptive statistics with medians, proportions of evaluable patients and Kaplan-Meier analyses were used. Results: A total of 56 pts with histologically confirmed NEPC were included (table). Minimum and median follow up were 4.2 and 7.8 months, respectively. At the time of prostate cancer (PCa) diagnosis, the median age was 62 years, 66% of the pts were primarily metastatic of whom 51% had high volume disease according to CHAARTED criteria. A positive family history of PCa or other malignancies was present in 38% and 46% of the pts, respectively. 50% of the pts reported current or previous nicotine abuse. Pure neuroendocrine histology was found in 64% of the biopsies at NEPC diagnosis. Pts who developed a treatment emergent (t)NEPC in the course of disease (n=39) received ADT monotherapy (41%) or an intensified treatment with an androgen receptor pathway inhibitor (ARPI) (33%), docetaxel (23%) or triple therapy with darolutamide and docetaxel (3%) in the hormone-sensitive stage. Median time to castration resistance was 17 months, with 41% of the patients experiencing a direct transition to NEPC. At initial diagnosis of NEPC, 93% of the patients were started on 1 st line chemotherapy of whom 92% received a platinum-based combination with etoposide. However, 33% of these pts showed primary radiographic progression or did not receive imaging due to rapid deterioration. Significantly fewer pts were exposed to 2 nd , 3 rd , or 4 th therapy (46%, 25% and 14%). Median progression free survival (PFS) from 1 st , 2 nd , 3 rd and 4 th line therapy in NEPC was 3.7, 2.8, 2.7 and 1.8 months, respectively. Median overall survival (OS) from the time of diagnosis of NEPC was 8.5 months, with 61% of patients dying within the first year. Conclusions: Prognosis of NEPC pts remains poor with rapid progression through multiple lines of treatment and most patients dying within 1 year of diagnosis. This highlights the great need for new therapeutic strategies for pts with NEPC. Baseline characteristics and clinical outcomes of pts with NEPC. NEPC (n=56) tNEPC(n=39) de novo NEPC (n=17) Median age at 1st diagnosis of PCa (years) 62 62 62 Primary metastatic [%] 66 56 88 High volume according to CHAARTED criteria at initial diagnosis [%] 37 29 53 Pure neuroendocrine histology at initial diagnosis of NEPC [%] 64 64 60 Family history PCa [%] 38 38 38 Family history other cancers [%] 46 38 63 Nicotine abuse (%) 50 53 46 Median PFS 1st line therapy (Q1; Q3) [months] 3.7 (2.1-6.5) 3.1 (1.6-6.5) 5.2 (3.7-5.6) Median OS (Q1; Q3) [months] 8.5 (4.2-14.2) 7.2 (3.0-12.8) 14.2 (6.5-18.6)