A contemporary nationwide analysis of neoadjuvant regimens for esophageal adenocarcinoma

In the United States, neoadjuvant chemoradiotherapy with CROSS (41.6 Gy, carboplatin/paclitaxel) has been the standard for patients with operable locally advanced esophageal adenocarcinoma (EAC). Recently, the ESOPEC multicenter phase III trial reported superior overall survival (OS) with perioperative FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) compared to CROSS. We aimed to examine trends in neoadjuvant treatment strategies and compare outcomes in a contemporary real-world cohort.

Patients with clinical stage II-IVA (T2-4aN0-3M0 by the American Joint Committee on Cancer 8th Edition staging classification) EAC who underwent neoadjuvant chemoradiation (nCRT; ≥41.4 Gy) or neoadjuvant chemotherapy (nCT) followed by esophagectomy were identified in the National Cancer Database (2015-2022). Postoperative outcomes and overall survival (Kaplan-Meier) were compared in propensity-matched cohorts.

A total of 9845 patients were identified, of whom 8955 (91.0%) received nCRT and 890 (9.0%) received nCT before esophagectomy. The median patient age was 65 years (interquartile range [IQR], 58-71 years), and 88.1% (n = 8674) of the patients were male. Over time, there was trend toward increasing use of nCT, from 6.7% of patients in 2015 to 9.6% in 2022 (P < .001). In well-balanced matched cohorts (1:1, nCT vs nCRT; n = 106), despite an improved pathologic response with nCRT, nCT was associated with improved OS (median, 51.4 months vs 40.5 months; P = .029; hazard ratio, 0.82; 95% confidence interval, 0.68-0.98) and a better 5-year OS rate (49.8% vs 43.3%) at a median follow-up of 28.8 months (IQR, 17.2-42.5 months).

In a contemporary cohort of patients with locally advanced EAC, nCRT remained the predominant approach. However, consistent with ESOPEC, nCT alone was associated with improved OS.