Outcomes of Neoadjuvant Chemoradiation in Clinical Stage I-II Esophageal Cancers with Signet Ring Histology

Abstract ABSTRACTPurpose: Esophageal signet ring cell carcinoma (SRC) is a rare subtype of esophageal adenocarcinoma associated with aggressive biology and poor outcomes. The role of neoadjuvant chemoradiation (NCRT) in clinical stage I-II esophageal SRC remains poorly defined.Methods: Patients with clinical stage I-II (cT1-2N0, cT1N1) esophageal SRC who underwent esophagectomy between 2004 and 2017 were identified from the National Cancer Database. Patients were stratified by receipt of NCRT followed by esophagectomy versus upfront surgery. Overall survival was evaluated using Kaplan–Meier analysis and the log-rank test. Multivariable Cox proportional hazards regression assessed the association between NCRT and survival after covariate adjustment.Results: Of 198 patients, 88 (44.4%) received NCRT and 110 (55.6%) underwent upfront surgery. Patients receiving NCRT presented with more advanced disease preoperatively. Postoperative T stage differed between groups, with higher rates of residual pT3 disease following NCRT. Median overall survival was significantly shorter among patients receiving NCRT compared with upfront surgery (36.1 vs. 68.2 months; p=0.038). In subgroup analysis, upfront surgery was associated with improved survival in cT1 disease (97.5 vs. 26.9 months; p=0.008), with no difference observed in cT2 disease (36.1 vs. 33.4 months; p=0.790). On multivariable analysis, NCRT remained independently associated with worse overall survival (HR 1.62, 95% CI 1.05–2.50, p=0.030).Conclusion: In this national cohort of patients with clinical stage I-II esophageal SRC, NCRT was associated with inferior overall survival compared with upfront surgery. These findings suggest standard neoadjuvant approaches may not benefit this aggressive subtype and highlight the need for histology-specific treatment strategies.