Neoadjuvant treatment of esophageal cancer: chemotherapy, chemoradiation, immunotherapy, and future trends of therapy.

In the Western hemisphere, nonmetastatic locally advanced esophageal carcinoma is mostly treated in multimodal therapy protocols according to current therapy guidelines. In squamous cell carcinoma of the esophagus, neoadjuvant chemoradiation is the favorable option. Unimodal surgical and chemoradiation treatment alternatives show inferior results on this entity. For locally advanced adenocarcinoma of the esophagus perioperative chemotherapy and neoadjuvant chemoradiation have been competing treatment approaches in the recent past. Both are evidence based (class I evidence) and superior compared to unimodal surgery. However, the latest results of head-to-head comparative therapy studies show superior overall survival results for the FLOT regimen of perioperative chemotherapy. Furthermore, immunotherapy and targeted therapy with monoclonal antibodies have become a strong focus of current clinical research. Nivolumab as well as trastuzumab are already an important part of the current standard therapies. In both entities - SCC and AC - a significant quota of patients shows a locoregional complete remission of the tumor in the specimen after modern neoadjuvant therapy and surgical resection. The addition of immunotherapy and targeted therapy to neoadjuvant therapy further increases complete remission rates in defined subgroups according to the results of current studies. Currently, three prospective randomized trials are ongoing on the subject of future possibilities for organ-preserving concepts in case of complete clinical remission ("surgery as needed," "watch and wait"). It is to be expected for the future that curative short-term and long-term treatment results in locally advanced esophageal carcinoma will significantly improve, particularly due to the additional possibilities of immunotherapy and organ-preserving therapy concepts in postneoadjuvant complete remission.