New Frontiers in the Treatment of Rectal Cancer

For decades, the management of locally advanced rectal cancer has been trimodal therapy with radiotherapy, surgery, and chemotherapy. Collectively, the adoption of total neoadjuvant therapy (TNT), advances in how radiotherapy and chemotherapy are administered, and the introduction of immunotherapy for patients with mismatch repair-deficient tumors have revolutionized the treatment paradigm of locally advanced rectal cancer, most notably by making nonoperative management possible in up to half of patients. Here, we highlight landmark studies that inform the use of TNT. We then discuss ongoing research efforts and future directions in the field with the ultimate goal of improving both survival and quality of life for patients with locally advanced rectal cancer.