This contemporary review of esophageal cancer recognizes adenocarcinoma is increasingly prevalent in Western populations while squamous-cell carcinoma remains dominant worldwide. Major risk factors differ by histology, with reflux and obesity strongly linked to adenocarcinoma and tobacco and alcohol particularly important for squamous-cell carcinoma. Early detection remains challenging because dysphagia and weight loss occur late, although endoscopic screening of selected high-risk patients (age 50+ with chronic reflux) and ongoing surveillance of those with noted Barett’s provide opportunities for prevention and earlier diagnosis. When it comes to the use of chemoradiation: it is favored as definitive therapy for proximal SCC, is used as either adjuvant or stand-alone therapy for more distal SCC, and has recently been supplanted by peri-operative FLOT + durvafor resectable adenocarcinoma though remains a viable option as definitive management for adenocarcinoma that will not be resected. Finally, the small minority of mismatch-repair deficient tumors are potentially eligible for immunotherapy alone, and systemic therapy selection for metastatic disease is increasingly biomarker-driven (e.g., HER-2, PD-L1, claudin 18.2). | Xie, N Engl J Med 2026
