Characterizing esophageal mixed neuroendocrine-non-neuroendocrine neoplasms: insights from a retrospective multicenter study of clinical outcomes and prognostic indicators.

Background: The esophageal mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) is an extremely rare but poor prognosis tumor.

Objectives: This retrospective study aimed to analyze the clinical characteristics of MiNEN and to investigate postoperative survival and prognostic factors.

Design: This retrospective study analyzed 69 patients diagnosed with esophageal MiNEN at two major esophageal cancer centers in China from January 2000 to December 2021.

Methods: We assessed demographic data, tumor characteristics, treatment modalities, and survival outcomes. Statistical analyses included Kaplan-Meier survival curves and Cox regression models to evaluate prognostic factors.

Results: The most common histological types were combinations of small-cell carcinoma and squamous carcinoma (91.3%). The correct diagnostic rate of preoperative pathologic biopsy was only 4.3%. The median overall survival (OS) was 24.0 months, and disease-free survival (DFS) was 16.6 months. The 1-, 3-, and 5-year survival rates were 84.1%, 34.8%, and 25.3%, respectively. A peak period of recurrence or metastasis occurs in the first year after surgery, and regional lymph node recurrence is the main route of postoperative recurrence or metastasis. Tumor size, T-stage, N-stage, and tumor, lymph node, metastasis (TNM) stage were significant prognostic factors. Subgroup analyses showed that in patients with limited-stage MiNEN in stages I-III, the postoperative adjuvant treatment modality failed to improve OS and DFS compared with surgery alone. Postoperative adjuvant therapy also failed to prolong OS and DFS in patients with lymph node-positive MiNEN. No significant survival benefits were observed with different surgical techniques or adjuvant chemotherapy regimens.

Conclusion: Esophageal MiNEN has aggressive behavior and a poor prognosis. In China, the pathologic type of esophageal MiNEN may be dominated by a combination of small-cell carcinoma and squamous carcinoma. Early-stage disease significantly correlated with improved survival outcomes. Current treatment protocols, similar to those for other esophageal cancers, show limited efficacy in improving patient survival.