Comparison of the Clinical Features and Outcomes of Gallbladder Neuroendocrine Carcinoma with Those of Adenocarcinoma: A Propensity Score-Matched Analysis

SIMPLE SUMMARY: Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are extremely rare. We aimed to compare the clinical features of GB-NENs with those of adenocarcinomas (ADCs) of the GB. Among 21 patients with GB-NENs, 20 were diagnosed with poorly differentiated small-cell neuroendocrine carcinoma (NEC), and 1 patient had large-cell NEC. At initial presentation, all patients had advanced stages of cancer, with extensive local extension and/or distant metastasis. Nine patients with GB-NEC who underwent surgical resection had a significantly better progression-free survival (PFS) than those who did not undergo surgery. After a propensity score matching with a 1:1 ratio using the American Joint Committee on Cancer (AJCC) stage, age, sex, and operation status, there was no difference in the overall survival or PFS between AJCC stage-matched patients with GB-NEC or GB-ADC. In conclusion, GB-NEC is difficult to diagnose early and has a prognosis similar to that of GB-ADC. ABSTRACT: Neuroendocrine neoplasms (NENs) of the gallbladder (GB) are extremely rare. We aimed to compare the clinical features, disease progression, management, and prognosis of patients with GB-NENs with those of patients with GB-adenocarcinomas (ADCs). A total of 21 patients with GB-NENs and 206 patients with GB-ADCs, treated at three tertiary medical centers between January 2010 and December 2020, were enrolled. Of the 21 patients with GB-NENs, 20 were diagnosed with poorly differentiated small-cell neuroendocrine carcinomas (NECs), and 1 patient had large-cell NEC. All patients presented with advanced stages of cancer with extensive local extension and/or distant metastasis and non-specific symptoms. Tumor-node-metastasis stage IIIB and IV (A/B) tumors were found in 6 and 15 (1/14) patients, respectively. Nine patients with GB-NEC who underwent surgical resection had a significantly better progression-free survival (PFS) than those who did not undergo surgery. After a propensity score matching with a 1:1 ratio using the American Joint Committee on Cancer stage, age, sex, and operation status, 19 pairs of patients were included. Compared with stage-matched patients with GB-ADC, patients with GB-NEC had similar overall survival and PFS. However, as GB-NEC is rarely diagnosed early, further studies investigating methods for the early diagnosis and improvement in the survival of patients with GB-NEC are needed.