Currently, the most promising strategy to improve the prognosis of advanced
esophageal cancer is
neoadjuvant chemoradiation (CRT) followed by surgery. However, patients who achieved pathological complete response can experience more survival benefit. Therefore, it is critical to identify the responders early in the course of treatment. Published data demonstrate that clinic-histopathological factors, molecular
biomarkers, and functional imaging are predictive of
neoadjuvant therapy. The existing
biomarkers, including
epidermal growth factor receptors, angiogenetic
factors, transcription factors, tumor suppressor genes, cell cycle regulators, nucleotide excision repair pathway,
cytokines, and
chemotherapy associated genes, need to be validated and novel
biomarkers warrant further exploration. Positron emission tomography (PET) is useful for differentiating the responders of neoadjuvant CRT. The most valuable parameters and the time point of performing PET in the course of treatment remains to be elucidated. Furthermore, predictive models incorporating the multiple categories of factors need to be established with a large, prospective, and homogeneous patient cohort in the future. Standardization of staging,
biomarker detection method, and image acquisition protocol will be critical for the generalization of this model. Prospective, multi-center controlled trials, which stratified patients according to these predictive factors, will help guide individualized treatment strategies for patients with
esophageal cancer.