A Comprehensive Review of Randomized Clinical Trials Shaping the Landscape of Rectal Cancer Therapy

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 might be appropriate for a subset of patients with early-stage, superficial tumors, the standard of care for medically operable patients with nonmetastatic rectal cancer includes a comprehensive multimodality approach of neoadjuvant chemoradiotherapy, surgery with total mesorectal excision, and systemic chemotherapy. However, the morbidity and mortality related to both local and distant organ relapse have remained challenging. In the present review, we have discussed the trial-level evidence that has shaped the current clinical practice patterns in the treatment of curable, nonmetastatic rectal cancer. In addition, we have discussed the anticipated results of ongoing clinical trials and outlined 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.