Evolving Treatment Options and Future Directions for Locally Advanced Rectal Cancer

Locally advanced rectal cancer can be biologically heterogeneous, but imaging advances have improved clinical assessment of primary tumor and involved lymph nodes in relation to pelvic structures and intended surgical planes. Contemporary treatment for rectal cancer is tailored to the individual patient through multidisciplinary collaboration among diagnosticians, surgeons, medical oncologists, and radiation oncologists to minimize local recurrence and distant metastases. Furthermore, patient preferences and quality of life preservation are becoming more relevant in the decision-making, and upcoming treatment strategies specifically are designed to minimize toxicities and long-term morbidity. Accumulating data have continued to support the use of total neoadjuvant therapy, namely the completion of: (1) multiagent cytotoxic chemotherapy; and (2) pelvic radiation with or without a radiosensitizing agent, before surgery. The total neoadjuvant therapy strategy not only eliminates potentially occult metastases early but also opens up the possibility of nonsurgical management for those who decline or are unfit for surgery. Finally, noncytotoxic agents in combination with established chemotherapy agents along with potentially predictive biomarkers are also being actively investigated to further improve the clinical outcomes of rectal cancer.