Neoadjuvant therapy linked to higher mortality in early esophageal adenocarcinoma: a national cohort study

The benefit of neoadjuvant therapy in early-stage esophageal adenocarcinoma, particularly clinical T1N0 tumors, remains uncertain. Although neoadjuvant therapy is standard for locally advanced disease, its role in early-stage cases is less clear. This study evaluated outcomes of endoscopic mucosal resection (EMR), upfront esophagectomy, and neoadjuvant therapy followed by surgery.

We analyzed the National Cancer Database (2018-2022) for adult patients with cT1N0M0 esophageal adenocarcinoma. Patients were grouped by initial treatment: EMR, upfront esophagectomy, or neoadjuvant therapy followed by surgery. Exclusions included patients with advanced staging, metastases, nonadenocarcinoma histology, or palliative care. The primary outcomes included length of stay (LOS), 30- and 90-day mortality, and overall survival. Multivariable Cox regression was adjusted for demographics, comorbidities, facility type, and tumor characteristics.

Among 1179 patients, 15 (1.3%) underwent EMR, 977 (82.9%) underwent upfront esophagectomy, and 187 (15.9%) received neoadjuvant therapy with surgery. Patients receiving neoadjuvant therapy had a shorter median LOS (8 vs 9 days, P <.001) but higher 90-day mortality (7.5% vs 4.1%, P = .005). On multivariable analysis, neoadjuvant therapy was associated with worse overall survival than upfront surgery (hazard ratio, 1.77; 95% CI, 1.24-2.52; P = .002). No significant survival differences were observed when comparing either upfront surgery or neoadjuvant therapy + surgery with EMR. In patients with clinical T1b, node negative (cT1bN0) subgroup, neoadjuvant therapy was again associated with higher 90-day mortality and worse adjusted survival.

Among patients with cT1N0 esophageal adenocarcinoma, neoadjuvant therapy followed by surgery was associated with increased perioperative mortality and worse survival compared with upfront esophagectomy in this retrospective cohort. EMR showed favorable short-term outcomes, although the small sample size limited conclusions. Further study is warranted in selected early-stage patients.