Abstract

Abstract Curative treatment for esophageal cancer requires local and systemic disease control. Neoadjuvant treatment increases long-term survival, but the evidence to date is insufficient to determine if neoadjuvant chemoradiotherapy (nCRT) with focus on local control or neoadjuvant chemotherapy (nCT) with focus on systemic control, is more beneficial. In this analysis of the ENSURE study we aimed to compare recurrence patterns and survival between nCRT and nCT in a large multicenter European cohort study. All patients treated with neoadjuvant therapy and esophagectomy for cancer from 2009-2015 in the ENSURE study (NCT03461341) were included. Univariable and multivariable logistic regression and Cox proportional hazard models were used to compare recurrence pattern, diseases-free, and overall survival. Results are shown as odds ratios (OR), hazard ratios (HR) and 95% confidence intervals (CI). The multivariable model was pre-specified and included age, sex, clinical tumor stage, and tumor histology. In total 3267/4682 (69.8%) patients were treated with neoadjuvant therapy and were included in the study. nCRT was given to 1798 (55.0%) patients, and nCT was given to 1496 (45.0%) patients. Median age for nCRT was 63 vs. 64 for nCRT, 65.5% in the nCRT group had adenocarcinoma vs. 81.4% in the nCT group. In the nCRT group 38.7% of patients had tumor stage III-IV compared to 61.3% in the nCT group. Multivariable adjusted OR for local recurrence comparing nCRT to nCT was 1.31 (95% CI: 1.08-1.59), distant recurrence OR 1.87 (95% CI: 1.57-2.22), and combined recurrence 1.49 (95% CI: 1.26-1.76). Adjusted HR for disease specific survival comparing nCRT to nCT was 1.38 (95% CI: 1.24-1.55), disease free survival: 1.39 (95% CI: 1.25-1.54), and for overall survival: 1.44 (95% CI: 1.30-1.60). The results of the study show significantly increased risk for recurrent disease and decreased survival after nCRT compared to nCT for esophageal cancer. nCRT is administered with a lower total dose of chemotherapy compared to nCT. Radiotherapy is given for local control, which is also achieved with adequate lymphadenectomy. The results indicate that effective systemic treatment with nCT might be beneficial compared to nCRT in curative intended treatment of esophageal cancer.

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