Abstract
Combined-modality therapy, using radiotherapy and chemotherapy with surgery, has been the traditional therapeutic algorithm for locally advanced rectal cancer. Standard of care in the United States has evolved to include neoadjuvant concurrent chemotherapy and radiotherapy followed by surgical excision and adjuvant chemotherapy. This approach has led to a significant improvement in local recurrences (LR), to the point where distant sites are the more common site of failure. Further improvements in local control have failed to improve overall survival. This article reviews historical trials that shifted the treatment paradigm to the current standard of care, as well as recent research trials, which have sought to incorporate new treatment methodologies, and treatment agents to improve outcomes. Finally this article describes ongoing studies and their potential impact on the future of therapeutic management of locally-advanced rectal cancer.