Abstract
The optimal management of locally advanced rectal cancer (LARC) often presents a therapeutic challenge. Balancing the benefits of treatment against toxicities and reducing the risk for local and distal recurrences are the mainstay of therapeutic approaches. Recently, several studies have compared a more aggressive approach of delivering several cycles of systemic chemotherapy to the established standard of combined chemoradiation. This approach is termed total neoadjuvant therapy and appears to be beneficial, at least for a subset of patients. The results of the main Phase III studies along with their variations in study design are hereby discussed with the goal of extracting useful clinical suggestions for treatment.