The Expansion of Curative Treatment Options for Locally Advanced Rectal Cancer as a Model for the Translation of Personalized Medicine

Abstract The management of locally advanced rectal cancer (LARC) has witnessed a relatively rapid expansion of treatment options. Previously, most patients were treated with radiation therapy, surgery, and adjuvant chemotherapy regardless of tumor stage, molecular characteristics, or patient preference. It was long recognized that each treatment modality can negatively impact the well-being and quality of life of long-term survivors and that many patients were probably being overtreated. Fortunately, many thoughtful and practice-changing clinical trials have revolutionized the management of LARC and conclusively shown that not all patients require trimodality therapy. Omission of surgery or radiation is feasible for appropriately selected patients with adequate responses to neoadjuvant therapies, and many patients with tumors that harbor microsatellite instability mutations can be adequately treated with immunotherapy alone. Many patients with LARC have multiple treatment options, and selection of the most appropriate therapy requires careful consideration of their tumor characteristics and personal priorities. In many ways, LARC has been an excellent example of the practical application of personalized medicine in the curative setting. This review will provide an overview of the key advances that have shaped the current treatment options and highlight ongoing studies that are expected to provide further clarity for existing knowledge gaps.