The Key Clinical Questions of Neoadjuvant Chemoradiotherapy for Resectable Esophageal Cancer—A Review

Over 50% of individuals with esophageal cancer (EC) present with advanced stages of the disease; therefore, their outcome following surgery alone is poor, with only 25%–36% being alive 5 years post-surgery. Based on the evidence that the CROSS and NEOCRTEC5010 trials provided, neoadjuvant chemoradiotherapy (nCRT) is now the standard therapy for patients with locally advanced EC. However, there are still many concerning clinical questions that remain controversial such as radiation dose, appropriate patient selection, the design of the radiation field, the time interval between chemoradiotherapy (CRT) and surgery, and esophageal retention. With immune checkpoint inhibitors (ICIs) rapidly becoming a mainstay of cancer therapy, along with radiation, chemotherapy, and surgery, the combination mode of immunotherapy is also becoming a hot topic of discussion. Here, we try to provide constructive suggestions to answer the perplexing problems and clinical concerns for the progress of nCRT for EC in the future.