The evolution of rectal cancer treatment: the journey to total neoadjuvant therapy and organ preservation

There has been a staggering increase in the incidence of rectal cancer, drawing our attention to early detection and optimization of its medical and surgical treatment. With this review we highlight all the major trials that revolutionized rectal cancer management and improved oncologic outcomes. We present the origins of the trimodal therapy and the studies that supported the sequence of treatment. We describe the evolution in surgical management with total mesorectal excision as the standard of care, and we review the most impactful short- vs. long-course long-course radiation therapy trials. Today, the current standard of care for non-metastatic locally advanced rectal cancer includes preoperative chemoradiation with either induction or consolidation chemotherapy, total mesorectal excision and adjuvant therapy. We discuss the advent of the "watch and wait" strategy for patients who have a complete clinical response after total neoadjuvant treatment, as well as possible future directions in the treatment of locoregional disease.