Therapeutic Management of Locally Advanced Rectal Cancer: Existing and Prospective Approaches

Rectal cancer (RC) presents significant challenges in diagnosis and treatment, with increasing incidence among younger populations. Treatment approaches, particularly for locally advanced rectal cancer (LARC), have evolved, notably with the introduction of total neoadjuvant therapy (TNT). TNT combines neoadjuvant chemotherapy and chemoradiotherapy before surgery, improving overall survival and reducing both metastasis and local recurrence rates compared to traditional methods, while enabling more patients to complete the full oncological treatment. Clinical trials, such as RAPIDO, OPRA, and PRODIGE 23, have demonstrated the effectiveness of TNT in tumor downstaging and complete pathological responses, offering better outcomes for patients; however, debates persist regarding the role of neoadjuvant radiotherapy, with novel strategies exploring its omission in specific cases to reduce toxicity and enhance quality of life. In addition, organ preservation strategies, such as the watch-and-wait (WW) approach, have emerged as viable options for patients with a complete response to neoadjuvant therapy. Future directions point towards personalized treatment plans incorporating radiogenomics and the integration of artificial intelligence into diagnostics to optimize patient outcomes. This review aims to synthesize current treatment strategies and ongoing advancements in rectal cancer management, providing insights into potential future innovations.