Chemotherapy and novel targeted therapies for operable esophageal and gastroesophageal junctional cancer.

During the past decades, several treatment strategies such as neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy and perioperative chemotherapy have been shown to improve the prognosis of resectable esophageal cancer. Patients with squamous cell tumors respond better to neoadjuvant chemoradiotherapy compared to adenocarcinoma. Therefore, in squamous tumors neoadjuvant chemoradiotherapy is the preferred strategy. Neoadjuvant chemoradiotherapy and perioperative chemotherapy are both effective in patients with adenocarcinoma. Chemoradiotherapy trials have shown higher rates of pCR, pN0 and R0 resection rates compared to neoadjuvant chemotherapy trials. Nonetheless, it is still unclear whether one strategy should be preferred over the other in terms of overall survival for adenocarcinoma. Based on the currently available evidence, the addition of targeted agents, such as VEGF and EGFR inhibitors, to the aforementioned strategies does not lead to survival benefit. Novel targeted treatment strategies that are currently being investigated include inhibition of HER2, PD-1 or the PD-1 ligand. Molecular subgroup analysis can contribute to better understanding of disease pathogenesis and prediction of response to treatment.