Abstract
BACKGROUND: Neuroendocrine carcinoma of the esophagus is a highly aggressive and rare type of cancer, making diagnosis and treatment challenging for clinicians. The current guidelines provide conflicting recommendations, and no standardized treatment protocol is available. We aim to deliver a systematic review of esophageal neuroendocrine carcinoma, including patient characteristics, treatment options, and prognostic factors. METHODS: PubMed, Web of Science, Scopus, and Embase were searched up to May 2025 to retrieve the relevant studies containing at least 5 cases that reported treatment details, survival outcomes, or patient characteristics. Meta-analysis was conducted using a random-effects model for prognostic factors reported in at least three studies. We calculated survival information using the Kaplan-Meier method and estimated the median 1, 3, and 5-year survival rates in studies with available individual data that did not directly report the survival outcomes. RESULTS: Overall, 24 articles with 1618 cases were included. The median overall survival of patients was 22.5 months, with median 1-, 3-, and 5-year survival rates of 76%, 47%, and 34%, respectively. Distant metastasis (HR, 2.68; 95% CI: 2.10 to 3.41; P < .01) and lymph node involvement (HR, 1.44; 95% CI: 1.04 to 1.99; P = .02) were significantly associated with poor prognosis. Surgery in selected cases improved the survival outcomes with an HR of 0.36 (95% CI, 0.28 to 0.46; P = < .01). CONCLUSION: The current study demonstrates that distant metastasis and lymph node involvement are significant predictors of poor prognosis in esophageal neuroendocrine carcinoma. Survival outcomes were comparable between patients with resectable tumors undergoing surgery and those receiving definitive chemoradiotherapy, both of which outperformed chemotherapy alone or no treatment. While adjuvant therapy may improve survival in node-positive cases post-surgery, this evidence remains limited by small sample sizes in existing studies. Further large-scale, prospective studies are needed to validate optimal treatment strategies, particularly the role of multimodal therapy in advanced disease.