ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Hepato Pancreatic Biliary Cancers
This article is part of the Research TopicInnovative Approaches in Chemotherapy and Immunotherapy for Gastroenteropancreatic Neuroendocrine CarcinomaView all 4 articles
Clinical Management and Prognostic Determinants of Gallbladder Neuroendocrine Carcinoma: A Single-Institutional Analysis of 31 Cases
Provisionally accepted- 1Sichuan University West China Hospital Department of Biliary Surgery, Chengdu, China
- 2Sichuan University West China Hospital Department of Pathology, Chengdu, China
- 3Sichuan University West China School of Medicine, Chengdu, China
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graphical abstract (Created in https://BioRender.com) Background: Gallbladder neuroendocrine carcinoma (GB-NEC) is an exceptionally rare and highly aggressive malignancy, accounting for only 0.2% of gastrointestinal neuroendocrine neoplasms and 2.3% of gallbladder cancers. Due to its nonspecific clinical presentation and diagnostic challenges, most patients present with advanced disease at diagnosis, resulting in poor prognosis with median survival typically under 12 months. This study aimed to analyze clinicopathological characteristics and identify independent prognostic factors in GB-NEC patients. Methods: We conducted a retrospective cohort study of 31 histologically confirmed GB-NEC cases treated at a tertiary referral center between 2015-2024. Comprehensive data including demographic characteristics, tumor markers, pathological features (differentiation, Ki-67 index, invasion patterns), treatment modalities (surgical approach, chemotherapy regimens), and survival outcomes were analyzed. Statistical methods included Kaplan-Meier survival analysis, log-rank tests, and multivariate Cox proportional hazards regression models. Results: The cohort demonstrated median progression-free survival of 12 months and overall survival of 36 months. Multivariate analysis identified three independent poor prognostic factors: elevated alpha-fetoprotein (AFP) (HR 1.01, p=0.034), mixed neuroendocrine-non-neuroendocrine histology (HR 18.22, p=0.042), and delayed adjuvant chemotherapy (HR 15.62, p=0.006). Conclusion: This study establishes AFP elevation, mixed histology, and delayed chemotherapy as critical determinants of poor prognosis in GB-NEC. Our findings emphasize the importance of early diagnosis, aggressive surgical resection, and timely initiation of platinum-based adjuvant therapy.
Keywords: Gallbladder neuroendocrine carcinoma, Platinum-based chemotherapy, survival analysis, prognostic factors, Retrospective study
Received: 15 Aug 2025; Accepted: 29 Oct 2025.
Copyright: © 2025 Luo, Zhou, Wang, Saad, You and Jiang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: 
Zhen  You, youzhen@wchscu.cn
Dan  Jiang, danjiang@scu.edu.cn
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
