Treatment of T4 esophageal cancer. Definitive chemo-radiotherapy vs chemo-radiotherapy followed by surgery.

The outcome of patients with T4 esophageal cancer, defined as a tumor that invades neighboring structures (e.g., aorta, trachea, bronchus, and lung), is extremely poor. Despite recent advances in surgical techniques, these tumors are usually considered inoperable. Two distinct therapeutic options are currently available for T4 esophageal cancers: chemo-radiotherapy followed by surgery (CRT-S), which comprises esophagectomy following down-staging of the tumor by CRT, and definitive chemo-radiotherapy (D-CRT), which is designed to avoid esophagectomy by using maximum doses of irradiation. CRT-S is superior to D-CRT with respect to local control and short-term survival although CRT-S is associated with relatively higher perioperative mortality and morbidity. On the other hand, it is sometimes difficult to achieve local control with D-CRT and the treatment often results in fistula formation, though a complete response to CRT is often associated with better prognosis. Admittedly, the difference in the survival rate between the two modalities is marginal at long-term follow-up due to operative morbidity and inadequate control of distant metastasis in CRT-S. Changes in perioperative management and intensive systemic chemotherapy may enhance the outcome. Randomized controlled trials involving large population samples are needed to define the standard treatment for T4 esophageal cancer.