Evolving treatment paradigms in esophageal cancer

A heterogenous disease with a dismal prognosis, esophageal cancer poses a major health challenge worldwide. In recent years, the treatment landscape for esophageal adenocarcinoma and squamous cell carcinoma (SCC) has undergone major evolution, with the elucidation of underlying biologic pathways and predispositions. Neoadjuvant chemoradiation has emerged as a leading approach for the management of locoregional esophageal cancer, while perioperative chemotherapy has shown promising outcomes specifically in adenocarcinoma of the lower esophagus and gastroesophageal junction (GEJ). Studies also explore the implementation of chemoradiation in various sequential preoperative strategies, as well as in the adjuvant setting. Definitive chemoradiation is considered a valid alternative for non-surgical candidates with SCC. Clinical trials currently evaluating the potential benefits of different approaches may shed light on existing controversies regarding optimal management of locoregional disease. For patients with metastatic cancer, chemotherapy remains the backbone of antineoplastic treatment alongside palliative care, moreover the discovery of novel biological targets has led to the initiation of targeted and immune therapy for specific subpopulations. Taken together, an era of burgeoning clinical trials and changing paradigms has evolved in esophageal oncology. Multidisciplinary collaboration is key to effective combination and sequencing of treatment modalities tailored per patient and per tumor histology. This work aims to provide a comprehensive overview of state-of-the-art oncological management of esophageal cancer, with consideration of new challenges and obstacles to be overcome.