Extensive-stage small cell esophageal carcinoma: a retrospective analysis of treatment modalities

BACKGROUND: This study aimed to investigate the clinicopathological features, treatment strategies and outcomes, failure patterns, and prognostic factors impacting progression-free survival (PFS) and overall survival (OS) in patients with extensive-stage primary small cell esophageal carcinoma (ES-SCEC). METHODS: This retrospective study included consecutive patients with ES-SCEC diagnosed and treated at Fudan University Shanghai Cancer Center from January 2006 to December 2024. Clinicopathological data related to diagnosis, staging, and follow-up were collected. In patients with available tumor specimens, immunohistochemistry (IHC) was performed to assess the expression of POU2F3 (POU class 2 homeobox 3), standard neuroendocrine markers, thyroid transcription factor-1 and Ki-67. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors, with statistical significance defined as a two-sided p value < 0.05. RESULTS: Among the 112 patients with ES-SCEC, the median PFS was 5.0 months (95% CI: 4.4-5.6), and the median OS was 9.0 months (95% CI: 7.9-10.1). Liver metastasis was the most common metastatic site at initial diagnosis (58.9%). The use of immune checkpoint inhibitors (ICIs), the number of chemotherapy (CT) cycle and T stage were identified as independent prognostic factors for OS. Independent predictors of PFS included T stage, CT cycle, and thoracic radiotherapy (TRT). The overall response rate (RR) was 52.7%, and the disease control rate (DCR) was 90.2%. Patients receiving CT combined with ICIs (n = 33) achieved significantly longer median OS than those who not treated with ICIs (n = 72) (13.8 months vs. 8.8 months, p = 0.029). Patients treated with TRT (n = 36) demonstrated improved local control and longer median PFS compared with those not receiving TRT (n = 69) (7.9 months vs. 4.1 months, p < 0.001). The combination of CT, ICIs, and TRT was associated with favorable outcomes, with median PFS and OS of 10.1 and 16.9 months, respectively. CONCLUSION: The addition of ICIs to CT may be associated with improved survival in patients with ES-SCEC. This findings warrant validation in larger cohorts and prospective randomized studies.