Current Trends in the Treatment of Locally Advanced Rectal Cancer: Where We Are and How We Got Here

Purpose of Review The trimodal treatment for LARC-surgery, radiotherapy, and chemotherapy-has been the standard of care for more than 30 years but is facing fresh challenges. Major contemporary developments include the delivery of full systemic chemotherapy in the preoperative period, with or without chemoradiation (total neoadjuvant therapy or "TNT"), and the withholding of surgery for patients who achieve a complete clinical response (cCR) to initial treatment ("watch-and-wait"). We review the historical development of these trends and propose an approach to LARC treatment that integrates newly emerging protocols with the traditional standard of care. Recent Findings Data from the recent randomized trials PRODIGE 23 and CAO/ARO/AIO-12 show that patients with LARC treated with TNT have a higher frequency of cCR, longer disease-free survival, and increased ability to tolerate chemotherapy. Preliminary results of the prospective OPRA study indicate that a watch-and-wait approach may permit sphincter preservation for a high proportion of patients without compromising survival. The increasing adoption of TNT to treat LARC is due to high rates of cCR, low levels of toxicity, a superior ability to deliver full-dose chemotherapy, and better preservation of quality of life. Based on current evidence, the combination of preoperative systemic chemotherapy and non-surgical management is appropriate for selected patients who have achieved a cCR and face a high risk of sphincter loss or dysfunction with surgery.