Abstract

Abstract Background nCT and nCRT are the standard of care for locally advanced esophageal cancer (LAEC) treated with curative intent. However, no published randomized controlled trial to date has demonstrated superiority of either approach. This study aimed to compare clinicopathologic, oncologic and health-related quality of life (HRQL) outcomes following neoadjuvant chemoradiation (nCRT) and chemotherapy (nCT) in the ENSURE international multicenter study. Methods ENSURE is an international multicenter study of consecutive patients undergoing surgery for LAEC (2009–2015) across 20 high-volume centers (NCT03461341). The primary outcome measure was overall survival (OS), secondary outcomes included histopathologic response, recurrence pattern, oncologic outcome, and HRQL in survivorship. Results 2211 patients were studied (48% nCT, 52% nCRT). pCR was observed in 4.9% and 14.7% (P < 0.001), with R0 in 78.2% and 94.2% (P < 0.001) post nCT and nCRT, respectively. Postoperative morbidity was equivalent, but in-hospital mortality was independently increased (HR 2.73, 95%CI 1.43–5.21, P = 0.002) following nCRT vs nCT. Probability of local recurrence was reduced (OR 0.71, 956% CI 0.54–0.93, P = 0.012), and distant recurrence free survival time reduced (HR 1.18, 95% CI 1.02–1.37, P = 0.023) after nCRT vs nCT, with no difference in OS among all patients (HR 1.10, 95% CI 0.98–1.25, P = 0.113). On subgroup analysis, patients who underwent R0 resection following nCT as compared with nCRT had improved OS (median 60.7, 95% CI 49.5–71.8 months, vs 40.8, 95% CI 42.8–53.4, P < 0.001). Conclusion In this European multicenter study, nCRT compared with nCT was associated with reduced probability of local recurrence but reduced distant recurrence free survival for patients with LAEC, without differences in overall survival. These data support tailored patient-specific decision-making in the overall approach to achieving optimum outcomes in LAEC.

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