Abstract
The standard treatments for locally advanced rectal cancer typically involved neoadjuvant therapy with either short-course radiation or long-course chemoradiation, followed by radical surgery and adjuvant chemotherapy. While the advancement of surgical techniques and the adoption of multimodal therapy have greatly contributed to reducing local failure, there has been limited improvement in overall survival, primarily due to the stagnation in systemic failure. In response to this challenge, a new strategy known as total neoadjuvant therapy (TNT) has emerged, involving the administration of both full-dose chemotherapy and radiation before surgery. It has shown promise in reducing systemic failure, enhancing tumor regression, and improving treatment adherence, ushering in a new era in the standard treatment of locally advanced rectal cancer. This review aims to summarize the evolution of multimodal treatments for locally advanced rectal cancer, ultimately converging into the current TNT strategy, and provides an assessment of the benefits and limitations of TNT based on available evidence, serving as a foundation for selecting the best treatment option.