Neoadjuvant chemotherapy with or without radiation versus upfront esophagectomy in small cell carcinoma of the esophagus: A national database analysis of overall survival.

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e16126 Background: Small cell carcinoma of the esophagus (SCCE) is a rare malignancy characterized by aggressive biology, with most patients presenting with metastatic disease. For patients with locoregional disease, esophagectomy is commonly performed; however, the role of neoadjuvant chemotherapy with or without radiation remains unclear, and no standard treatment approach has been established. Methods: The United States National Cancer Database was queried for adults diagnosed with esophageal cancer between 2004 and 2023. Patients with pathologically confirmed small cell neuroendocrine carcinoma of the esophagus without metastatic disease were identified. Patients were grouped by treatment strategy: upfront esophagectomy or neoadjuvant chemotherapy with or without radiation followed by surgery. Demographic and clinical characteristics were compared using Wilcoxon rank-sum and Fisher’s exact tests. Overall survival (OS) was estimated using Kaplan–Meier methods and compared using the log-rank test. Multivariable Cox proportional hazards regression was used to assess the association between treatment strategy and OS, adjusting for age and Charlson–Deyo Comorbidity Index (CDCC). Results: A total of 114 patients were included; 86% were White, 8% Black, and 6% were of other racial or ethnic groups. Fifty-nine patients (51.7%) received neoadjuvant therapy, while 55 (48.3%) underwent upfront esophagectomy. Most patients (74.5%) had a CDCC score of 0. Patients receiving neoadjuvant therapy were significantly younger than those undergoing upfront surgery (median age 59.2 vs 66.2 years, p < 0.001). Neoadjuvant chemotherapy with or without radiation was associated with significantly improved OS compared with upfront esophagectomy (median OS 28.6 vs 14.1 months; log-rank p = 0.04). On multivariable analysis, upfront esophagectomy demonstrated a non-significant trend toward higher mortality (HR 1.22; 95% CI 0.65–2.28; p = 0.54), while increasing age was independently associated with worse OS. Conclusions: In this retrospective national cohort of patients with non-metastatic SCCE, neoadjuvant chemotherapy with or without radiation was associated with improved overall survival compared with upfront esophagectomy. These findings support consideration of neoadjuvant therapy in the management of locoregional SCCE. Treatment group Median OS (months) (95% CI) Log-rank P Neoadjuvant treatment- chemotherapy/radiation 28.62 (20.44-73.30) 0.04 Upfront esophagectomy 14.13 (11.17-40.61)

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