Somatostatin Analogues Do Not Improve Survival in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Registry-Based Analysis with Ki-67 Stratification
7 affiliations
- 1Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, 8091 Zurich, Switzerland
- 2Department of Hematology and Oncology, Hirslanden Klinik Zurich, 8032 Zurich, Switzerland
- 3Department of Clinical Research, University of Bern, 3010 Bern, Switzerland
- 4Clinic for Radiology and Nuclear Medicine, Center for Neuroendocrine and Endocrine Tumors, University Hospital Basel, 4031 Basel, Switzerland
- 5ENETS Center of Excellence, University Hospital Basel, 4031 Basel, Switzerland
- 6Center of Endocrine and Neuroendocrine Tumors, Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, University of Basel, 4031 Basel, Switzerland
- 7Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, 3010 Bern, Switzerland
Abstract
Background/Objectives: The efficacy of somatostatin analogues (SSA) in Grade 3 (G3) neuroendocrine neoplasms (NEN) remains controversial, and registry data rarely permit a formal separation of NET G3 from neuroendocrine carcinoma (NEC). Methods: We analyzed 519 patients with G3 gastroenteropancreatic (GEP) NEN recorded in a national neuroendocrine tumor registry (data export 3 April 2025; 464 de novo G3, 55 transformed G3); bronchopulmonary primaries were excluded. A Ki-67 > 55%, entered as a time-varying indicator, served as a surrogate for NEC. Outcomes were compared using Kaplan–Meier and Cox proportional hazards models with all treatments and the Ki-67 > 55% indicator entered as time-varying covariates. Results: Among 410 patients with classifiable Ki-67, 256 (62.4%) ever had a Ki-67 > 55%. Ki-67 > 55% was associated with worse progression-free survival (PFS; HR 1.40, 95% CI 1.06–1.84; p = 0.016) and overall survival (OS; HR 1.65, 95% CI 1.15–2.37; p = 0.006). SSA use was not significantly associated with PFS (HR 1.32, 95% CI 0.85–2.04; p = 0.215) or OS (HR 0.91, 95% CI 0.54–1.56; p = 0.744). After adjustment for Ki-67, transformed G3 was associated with worse OS (HR 1.60, 95% CI 1.02–2.51; p = 0.040). Conclusions: SSA therapy was not associated with improved survival in G3 GEP-NEN. As this is an observational analysis subject to confounding by indication, these estimates do not establish a lack of biological efficacy of SSA. A Ki-67 threshold of 55% identified a prognostically distinct subgroup and explains why transformed G3 appears indolent: after adjustment, it was associated with worse overall survival. This finding rests on 55 patients with 29 deaths and is hypothesis-generating.
Related
- Genomic Landscape of Gastroenteropancreatic Neuroendocrine Neoplasms Using Panel Sequencing
- Clinicopathologic characteristics and survival outcomes of gastroenteropancreatic neuroendocrine neoplasms in Peru: A 15-year retrospective cohort study
- Recent Advances in the Management of Gastroenteropancreatic Neuroendocrine Tumors
- [177Lu]Lu-edotreotide versus everolimus for gastroenteropancreatic neuroendocrine tumours (COMPETE): a phase 3, multicentre, randomised, open-label, superiority trial
- Somatostatin Receptor Scintigraphy Aiding the Exclusion of Cardiac Sarcoidosis in a Patient with Duodenal Neuroendocrine Tumor who Developed Complete Atrioventricular Block
BibTeX
@article{siebenhuner2026somatostatin,
title = {{Somatostatin Analogues Do Not Improve Survival in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Registry-Based Analysis with Ki-67 Stratification}},
author = {Alexander R. Siebenhüner and Jean-Benoît Rossel and Emanuel Christ and Attila Kollár},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203357},
url = {https://www.mdpi.com/2072-6694/18/20/3357},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Somatostatin Analogues Do Not Improve Survival in Grade 3 Gastroenteropancreatic Neuroendocrine Neoplasms: A Registry-Based Analysis with Ki-67 Stratification
AU - Alexander R. Siebenhüner
AU - Jean-Benoît Rossel
AU - Emanuel Christ
AU - Attila Kollár
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203357
UR - https://www.mdpi.com/2072-6694/18/20/3357
AB - Background/Objectives: The efficacy of somatostatin analogues (SSA) in Grade 3 (G3) neuroendocrine neoplasms (NEN) remains controversial, and registry data rarely permit a formal separation of NET G3 from neuroendocrine carcinoma (NEC). Methods: We analyzed 519 patients with G3 gastroenteropancreatic (GEP) NEN recorded in a national neuroendocrine tumor registry (data export 3 April 2025; 464 de novo G3, 55 transformed G3); bronchopulmonary primaries were excluded. A Ki-67 > 55%, entered as a time-varying indicator, served as a surrogate for NEC. Outcomes were compared using Kaplan–Meier and Cox proportional hazards models with all treatments and the Ki-67 > 55% indicator entered as time-varying covariates. Results: Among 410 patients with classifiable Ki-67, 256 (62.4%) ever had a Ki-67 > 55%. Ki-67 > 55% was associated with worse progression-free survival (PFS; HR 1.40, 95% CI 1.06–1.84; p = 0.016) and overall survival (OS; HR 1.65, 95% CI 1.15–2.37; p = 0.006). SSA use was not significantly associated with PFS (HR 1.32, 95% CI 0.85–2.04; p = 0.215) or OS (HR 0.91, 95% CI 0.54–1.56; p = 0.744). After adjustment for Ki-67, transformed G3 was associated with worse OS (HR 1.60, 95% CI 1.02–2.51; p = 0.040). Conclusions: SSA therapy was not associated with improved survival in G3 GEP-NEN. As this is an observational analysis subject to confounding by indication, these estimates do not establish a lack of biological efficacy of SSA. A Ki-67 threshold of 55% identified a prognostically distinct subgroup and explains why transformed G3 appears indolent: after adjustment, it was associated with worse overall survival. This finding rests on 55 patients with 29 deaths and is hypothesis-generating.
SN - 2072-6694
ER -