Neoadjuvant chemoradiotherapy versus chemotherapy alone for locally advanced esophageal adenocarcinoma: A National Cancer Database analysis.

Abstract

302 Background: The optimal neoadjuvant strategy for resectable, locally advanced esophageal adenocarcinoma (EAC) remains debated. While pivotal trials have established neoadjuvant chemoradiotherapy (nCRT) as a standard of care, several recent studies suggest that neoadjuvant chemotherapy (nCT) alone may offer similar survival with reduced toxicity. However, comparative effectiveness in a large, real-world U.S. population is unknown. We utilized a national database to compare outcomes between patients receiving nCRT and nCT. Methods: We identified patients in the National Cancer Database (NCDB) from 2010-2020 with clinical stage II/III (cT2-4aN0-3M0) EAC who underwent esophagectomy. Patients were categorized as receiving multi-agent nCT or nCRT. To minimize selection bias, we performed 1:1 propensity score matching (PSM) based on patient demographics, comorbidities (Charlson-Deyo score), and tumor characteristics (cT stage, cN stage, grade). The primary endpoints were pathologic complete response (pCR) rate and 5-year overall survival (OS). OS was analyzed using the Kaplan-Meier method and Cox proportional hazards regression. Results: Of 8,542 eligible patients, 6,120 (71.6%) received nCRT and 2,422 (28.4%) received nCT. After PSM, 2,000 well-matched pairs were identified (Table 1). In the matched cohort, the pCR rate was significantly higher in the nCRT group compared to the nCT group (28.5% vs. 9.8%, p<0.001). Furthermore, nCRT was associated with a significant improvement in 5-year OS (45.2% vs. 38.6%; Hazard Ratio 0.82; 95% CI 0.75-0.90; p<0.001). Rates of positive surgical margins were also lower with nCRT (5.1% vs 9.3%, p<0.001). Conclusions: In this large, real-world analysis of patients with locally advanced EAC, neoadjuvant chemoradiotherapy was associated with significantly higher rates of pathologic complete response and improved long-term overall survival compared to neoadjuvant chemotherapy alone. These findings support the continued use of nCRT as a standard of care in this setting. Baseline patient and tumor characteristics before and after propensity score matching. Characteristic nCRT (unmatched) (N=6,120) nCT (unmatched) (N=2,422) SMD (unmatched) nCRT (matched) (N=2,000) nCT (matched) (N=2,000) SMD (matched) Age, median (IQR) 64 (57-71) 62 (55-69) 0.21 63 (56-70) 63 (56-70) 0.01 Male Sex, % 85.1 82.3 0.08 84.5 84.2 0.01 Charlson-Deyo 1+, % 35.2 28.9 0.14 33.1 33.5 0.01 cT3/T4a, % 78.5 65.4 0.30 71.2 71.0 <0.01 cN+, % 66.7 55.1 0.24 60.5 60.8 0.01 Grade 3, % 58.0 49.5 0.17 54.1 54.3 <0.01 SMD: Standardized Mean Difference; IQR: Interquartile Range.