Metastatic prostate cancer with neuroendocrine differentiation and liver metastases: prognosis and response to platinum-based chemotherapy.
10 affiliations
- 1School of Medicine and Health, Department of Nephrology, Technical University of Munich, TUM University Hospital, Ismaninger Str. 22, 81675, Munich, Germany. [email protected].
- 2Department of Hematology and Oncology, Martini‑Klinik, Prostate Cancer Center, University Cancer Center Hamburg, University Medical Center Hamburg- Eppendorf, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
- 3School of Medicine and Health, Department of Urology, Technical University of Munich, TUM University Hospital, Munich, Germany.
- 4School of Medicine and Health, Institute of Pathology, Technical University of Munich, Munich, Germany.
- 5School of Medicine and Health, Department of Nephrology, Technical University of Munich, TUM University Hospital, Ismaninger Str. 22, 81675, Munich, Germany.
- 6School of Medicine and Health, Department of Diagnostic and Interventional Radiology, Technical University of Munich, TUM University Hospital, Munich, Germany.
- 7Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg- Eppendorf, Hamburg, Germany.
- 8School of Medicine and Health, Department of Nuclear Medicine, Technical University of Munich, TUM University Hospital, Munich, Germany.
- 9German Cancer Consortium (DKTK), partnersite Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
- 10TUM School of Medicine and Health, Gynecological Tumor Genetics, Technical University of Munich, TUM University Hospital, Munich, Germany.
Abstract
Purpose
Neuroendocrine differentiation represents an aggressive prostate cancer subtype with poor prognosis. Platinum-based chemotherapy (PT) is standard of care, yet responses are often short-lived. This study aimed to define histopathological subgroups and identify predictors of survival in patients with liver-metastatic prostate cancer with neuroendocrine differentiation treated with PT.Methods
We retrospectively analyzed 950 patients with metastatic prostate cancer treated between 2006 and 2025, identifying 31 patients with neuroendocrine differentiation, liver metastases and PT. Tumors were classified into four subgroups based on the proportion of neuroendocrine features. Clinical characteristics, treatment response, tumor markers, and molecular alterations (TP53, RB1, PTEN, BRCA1/2) were evaluated. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox regression.Results
Median OS following PT initiation was 8.5 months. Disease control was achieved in 81% of patients, but responses were transient. Patients with a high proportion of remaining adenocarcinoma features showed the longest median OS (15 months), while pure neuroendocrine subtypes had the poorest outcomes (6-10 months). Osteolytic bone metastases (HR 2.48; 95% CI 1.08-5.72), TP53 loss-of-function variants (HR 2.43; 95% CI 1.14-5.16), and ≥ 2 concurrent alterations in TP53/RB1/PTEN (HR 2.13; 95% CI 1.03-4.41) were associated with inferior OS. Early reduction in liver metastasis size (HR 0.41; 95% CI 0.19-0.89) and decline in LDH (HR 0.50; 95% CI 0.23-1.09) after two treatment cycles predicted improved survival.Conclusions
Metastatic prostate cancer with neuroendocrine differentiation and liver metastases is characterized by extreme aggressiveness. There seems to be only limited durable benefit from PT especially in the presence of pure neuroendocrine morphology and tumor suppressor gene alterations. Therefore, these characteristics seem to be promising criteria to be investigated in larger prospective trials to further validate their clinical implications.
Related
- Case Report: Apparent progressive complete mismatch repair protein loss during platinum-based chemotherapy in metastatic rectal neuroendocrine tumour grade 2
- The Enemy of My Enemy: Two Cases of De Novo Metastatic Small-Cell Neuroendocrine Prostate Cancer with BRCA2 Alterations and Brain Metastases.
- Bone metastases identify a high-risk subgroup in metastatic neuroendocrine tumors with particular relevance in NETs of unknown primary
- Widespread Cutaneous Metastases as the Primary Presentation of an Occult Neuroendocrine Tumour of Unknown Primary
- Small Cell Neuroendocrine Carcinoma of the Bladder With Lymph Node Metastases: A Case Report
BibTeX
@article{schaaf2026metastatic,
title = {{Metastatic prostate cancer with neuroendocrine differentiation and liver metastases: prognosis and response to platinum-based chemotherapy.}},
author = {Christian W Schaaf and G von Amsberg and J J Werner and C Mogler and N Borcherding and N Pfarr and K Steiger and F Jungmann and L Steinhelfer and T Lorenzini and U A Schatz and J Steinhaus and L Renders and U Heemann and J Gschwend and M Retz and M Jahnen},
journal = {World journal of urology},
year = {2026},
month = oct,
doi = {10.1007/s00345-026-06859-3},
url = {https://europepmc.org/article/MED/42955315},
note = {CC BY},
}
RIS
TY - JOUR
TI - Metastatic prostate cancer with neuroendocrine differentiation and liver metastases: prognosis and response to platinum-based chemotherapy.
AU - Christian W Schaaf
AU - G von Amsberg
AU - J J Werner
AU - C Mogler
AU - N Borcherding
AU - N Pfarr
AU - K Steiger
AU - F Jungmann
AU - L Steinhelfer
AU - T Lorenzini
AU - U A Schatz
AU - J Steinhaus
AU - L Renders
AU - U Heemann
AU - J Gschwend
AU - M Retz
AU - M Jahnen
PY - 2026
DA - 2026/10/28
JO - World journal of urology
DO - 10.1007/s00345-026-06859-3
UR - https://europepmc.org/article/MED/42955315
AB - Purpose Neuroendocrine differentiation represents an aggressive prostate cancer subtype with poor prognosis. Platinum-based chemotherapy (PT) is standard of care, yet responses are often short-lived. This study aimed to define histopathological subgroups and identify predictors of survival in patients with liver-metastatic prostate cancer with neuroendocrine differentiation treated with PT.Methods We retrospectively analyzed 950 patients with metastatic prostate cancer treated between 2006 and 2025, identifying 31 patients with neuroendocrine differentiation, liver metastases and PT. Tumors were classified into four subgroups based on the proportion of neuroendocrine features. Clinical characteristics, treatment response, tumor markers, and molecular alterations (TP53, RB1, PTEN, BRCA1/2) were evaluated. Overall survival (OS) was analyzed using Kaplan-Meier estimates and Cox regression.Results Median OS following PT initiation was 8.5 months. Disease control was achieved in 81% of patients, but responses were transient. Patients with a high proportion of remaining adenocarcinoma features showed the longest median OS (15 months), while pure neuroendocrine subtypes had the poorest outcomes (6-10 months). Osteolytic bone metastases (HR 2.48; 95% CI 1.08-5.72), TP53 loss-of-function variants (HR 2.43; 95% CI 1.14-5.16), and ≥ 2 concurrent alterations in TP53/RB1/PTEN (HR 2.13; 95% CI 1.03-4.41) were associated with inferior OS. Early reduction in liver metastasis size (HR 0.41; 95% CI 0.19-0.89) and decline in LDH (HR 0.50; 95% CI 0.23-1.09) after two treatment cycles predicted improved survival.Conclusions Metastatic prostate cancer with neuroendocrine differentiation and liver metastases is characterized by extreme aggressiveness. There seems to be only limited durable benefit from PT especially in the presence of pure neuroendocrine morphology and tumor suppressor gene alterations. Therefore, these characteristics seem to be promising criteria to be investigated in larger prospective trials to further validate their clinical implications.
SN - 0724-4983
SN - 1433-8726
ER -