Epidemiologic Trends and Factors Associated With Overall Survival for Patients With Hepatobiliary Neuroendocrine Neoplasms in the United States.

backgroundNeuroendocrine neoplasms (NENs) constitute a heterogeneous group of rare tumors that most commonly originate from the gastrointestinal tract and lungs, with a consistently rising global incidence over recent decades. Hepatobiliary neuroendocrine neoplasms (HB-NENs), defined as primary NENs arising in the liver and biliary tract, are exceedingly uncommon, accounting for less than 0.5% of all NENs. Owing to their low incidence, atypical clinical presentations, and the paucity of large-scale datasets, no distinct World Health Organization (WHO) classification criteria have yet been established for these entities. Epidemiological characteristics and prognostic studies of HB-NENs remain extremely limited. Current prognostic evaluation relies predominantly on the American Joint Committee on Cancer (AJCC) and European Neuroendocrine Tumor Society (ENETS) TNM staging systems, whereas population-level investigations into incidence trends, survival determinants, and individualized predictive tools for HB-NENs are still largely absent.

aimsTo investigate epidemiological trends (1992-2020) and prognostic factors associated with overall survival in a nationally representative cohort of patients with hepatobiliary neuroendocrine neoplasms using the Surveillance, Epidemiology, and End Results registry, with subgroup stratification by sex and race. Additionally, we aim to develop a prognostic nomogram integrating significant predictors to quantify individualized survival probabilities for this population.

methodsIn this cohort study, patients diagnosed with hepatobiliary neuroendocrine neoplasms between January 1, 1975, and December 31, 2020, were identified from the Surveillance, Epidemiology, and End Results Program. Related data were used for epidemiologic and survival analysis, as well as the development and validation of a nomogram to predict the overall survival probability of individual hepatobiliary neuroendocrine neoplasms patients.

resultsThe age-adjusted incidence rate of hepatobiliary neuroendocrine neoplasms increased 1.76-fold from 1992 to 2020 (annual percentage change [APC], 2.73; 95% CI, 1.86-3.65; p < 0.05). Furthermore, the incidence of hepatobiliary neuroendocrine neoplasms in the extrahepatic bile duct increased most significantly (APC, 3.73; 95% CI, 2.03-5.46; p < 0.05), and the gallbladder also increased most significantly (APC, 3.51; 95% CI, 1.97-5.08; p < 0.05), whereas patients with hepatobiliary neuroendocrine neoplasms in the liver had no significant difference. As for tumor type, the incidence increased in hepatobiliary neuroendocrine carcinomas (APC, 2.93; 95% CI, 1.34-4.53; p < 0.05) but the incidence was stable in hepatobiliary neuroendocrine tumors. On multivariate analyzes, age at diagnosis, race, tumor size, grade, tumor type, tumor stage, and surgery were significantly associated with overall survival for hepatobiliary neuroendocrine neoplasms patients. Furthermore, a nomogram based on significant associated factors (age at diagnosis, race, tumor size, stage, type, grade, chemotherapy and surgery) was constructed to predict the 6-month, 1-year and 2-year survival probability, with the concordance indexes of 0.829 (95% CI, 0.800-0.857) for the training cohort and 0.801 (95% CI, 0.745-0.857) for the validation cohort.

conclusionIn this study, the incidence of hepatobiliary neuroendocrine neoplasms has exhibited a persistent upward trend over nearly two decades. Furthermore, this study proposes that a nomogram comprising eight prognostic parameters can effectively quantify the mortality risk in hepatobiliary neuroendocrine neoplasms patients.