Small cell carcinoma of the esophagus: A SEER-based analysis of stage-stratified radiotherapy outcomes and histologic comparisons.

362 Background: Primary small cell carcinoma of the esophagus (SCEC) is a rare and aggressive malignancy, representing <1% of esophageal cancers. Given its rarity, treatment strategies are largely extrapolated from small cell lung cancer. The role of radiotherapy (RT) across disease stages in SCEC, and how outcomes compare with adenocarcinoma and squamous cell carcinoma (SCC), remains poorly defined. Methods: The SEER 18 registries (2000–2022) were queried for patients with histologically confirmed esophageal carcinoma. Histology was grouped as SCEC (ICD-O-3: 8041/3, 8043/3, 8044/3, 8045/3), adenocarcinoma, or SCC. Patients with unknown survival time, non-first primaries, or missing treatment information were excluded. Overall survival (OS) was estimated using Kaplan–Meier methods and compared using log-rank tests. Analyses included SCEC patients treated with RT without surgery, stratified by SEER historic stage (localized, regional, distant), and comparisons across histologic subtypes. Multivariable Cox regression was used to calculate adjusted hazard ratios (HRs). Results: Among 56,126 patients with esophageal carcinoma, SCEC accounted for 403 (0.7%), adenocarcinoma for 66.4%, and SCC for 32.8%. Median OS for SCEC was 9 months (95% CI 8–10), significantly inferior to adenocarcinoma (11 mo, 95% CI 11–12, p <0.001) but not different from SCC (8 mo, 95% CI 8–9). In SCEC patients without surgery, median OS was 6 mo (95% CI 4–8) without RT versus 13 mo (95% CI 11–16) with RT ( p <0.001). Stage-stratified outcomes are summarized in the table: localized SCEC showed a marked OS benefit with RT (7 vs 48 mo, HR 0.18, 95% CI 0.07–0.44, p <0.001). For regional disease, OS was 8 vs 15 mo (HR 0.41, 95% CI 0.15–1.12, p =0.08), and for distant disease, 6 vs 10 mo (HR 0.70, 95% CI 0.46–1.07, p =0.10). Comparisons with non-SCEC histologies revealed that localized SCEC patients receiving RT achieved superior survival (48 mo) compared with 16 mo for both adenocarcinoma and SCC. Conclusions: SCEC is an exceptionally rare esophageal malignancy with poor outcomes relative to adenocarcinoma and SCC. RT provides a substantial survival advantage in localized SCEC, while its effect diminishes in regional and distant disease. These findings support stage-directed RT and highlight the need for prospective studies to optimize treatment in this rare cancer. Overall survival in small cell carcinoma of the esophagus (SCEC) with and without radiotherapy (RT) by stage. Subgroup Median OS without RT (mo) Median OS with RT (mo) HR (95% CI) p value All SCEC (no surgery) 6 (95% CI 4–8) 13 (95% CI 11–16) – <0.001 Localized SCEC 7 48 0.18 (0.07–0.44) <0.001 Regional SCEC 8 15 0.41 (0.15–1.12) 0.08 Distant SCEC 6 (95% CI 3–8) 10 (95% CI 8–13) 0.70 (0.46–1.07) 0.10