Controversies in the multidisciplinary management of locally advanced rectal cancer including total neoadjuvant therapy

Abstract Improvements in surgical techniques, radiotherapy strategies, and multidisciplinary team management have led to substantial reductions in the rate of locally recurrent rectal cancer. Emphasis has now shifted to more significant issues such as reducing the risk of distant metastases and facilitating non-operative management. In response, the field has witnessed the development and evolution of total neoadjuvant therapy, the preoperative delivery of chemotherapy in sequence with (chemo)radiotherapy. However, numerous controversies surround total neoadjuvant therapy, namely correct patient selection and the significant potential for overtreatment. In an attempt to spare patients from unnecessary drug, radiation, and surgical morbidity, adaptive trials have aimed to individualize treatment based on response rates. Unfortunately, there are currently no reliable biomarkers to aid the multidisciplinary team in selecting the optimal neoadjuvant treatment modalities. This chapter discusses the influential total neoadjuvant therapy trials, the concept of non-operative management, as well as controversies surrounding total neoadjuvant therapy in the elderly, adjuvant chemotherapy for locally advanced rectal cancer, and the evidence for immunotherapy in microsatellite unstable rectal cancer.