Perspectives on the pharmacological management of esophageal cancer: where are we now and where do we need to go?

Introduction: Esophageal cancer (EC) represents a complicated heterogenous group of malignancies. ECs are divided broadly into two types, histologically: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Historically, EC study designs have used bucket type groupings (all subtypes and/or all gastroesophageal cancers) reducing contribution to developing precision oncology. Areas covered: Surgery remains the curative modality for resectable disease with reasonable patient physiology. Trimodality is recommended for localized ESCC. An exception is cervical EC. For EAC, preoperative chemoradiation or perioperative chemotherapy is utilized. For those who undergo trimodality, nivolumab is recommended as an adjuvant therapy for those with a non-pathological complete response (pCR). Additionally, immunotherapy and other targets have been added to advanced EC treatment. Expert opinion: Organ sparing approaches for localized tumors are starting to be investigated in many solid tumors and have been standard approaches for decades in certain tumors (i.e. certain head and neck tumors and anal SCCs). pCR differs between esophageal histologies with trimodality indicating potential of discriminating localized approaches. To determine if a watch and wait approach is feasible, prospectively correlating clinical complete response to pCR is needed, determining the best active surveillance strategy, and the best use of tools like liquid biopsies.