A comprehensive review of randomized clinical trials shaping the landscape of rectal cancer therapy

ABSTRACT Colorectal carcinoma is the second leading cause of cancer-related deaths in the United States, with rectal cancer accounting for approximately one-third of newly diagnosed cases. Surgery remains the cornerstone of curative therapy with total mesorectal excision being the standard of care. Although minimally invasive procedures may be appropriate for a subset of patients with early-stage, superficial tumors, the standard of care approach for medically operable patients with non-metastatic rectal cancer includes a comprehensive multimodality approach of neoadjuvant chemoradiotherapy, surgery with total mesorectal excision, and systemic chemotherapy. However, morbidity and mortality related to both local and distant organ relapse remain a challenge. In this review, the authors discuss trial-level evidence that has shaped current clinical practice patterns in the treatment of curable, non-metastatic rectal cancer. In addition, we discuss anticipated results of ongoing clinical trials, as well as outline pragmatic opportunities for future investigation to optimize the current status quo, and hopefully provide prospective validation of novel approaches in the treatment of rectal cancer.