Clinical management and prognostic determinants of gallbladder neuroendocrine carcinoma: a single-institutional analysis of 31 cases.

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 3.90, p=0.042), and delayed adjuvant chemotherapy (HR 15.62, p=0.006). Discussion: 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.