Adoption of Total Neoadjuvant Therapy in the Treatment of Locally Advanced Rectal Cancer

Abstract

Local and metastatic recurrence are primary concerns following the treatment of locally advanced rectal cancer (LARC). Chemoradiation (CRT) can reduce the local recurrence rates and has subsequently moved to the neoadjuvant setting from the adjuvant setting. Pathological complete response (pCR) rates have also been noted to be greater in patients treated with neoadjuvant CRT prior to surgery. The standard approach to treating LARC would often involve CRT followed by surgery and optional adjuvant chemotherapy and remained the treatment paradigm for almost two decades. However, patients were often unable to complete adjuvant chemotherapy due to a decreased tolerance of chemotherapy following surgery, which led to upfront treatment with both CRT and chemotherapy, and total neoadjuvant therapy, or TNT, was created. The efficacy outcomes of local recurrence, disease-free survival, and pCR have improved in patients receiving TNT compared to the standard approach. Additionally, more recent data suggest a possible improvement in overall survival as well. Patients with a complete clinical response following TNT have the opportunity for watch-and-wait surveillance, allowing some patients to undergo organ preservation. Here, we discuss the clinical trials and studies that led to the adoption of TNT as the standard of care for LARC, with the possibility of watch-and-wait surveillance for patients achieving complete responses. We also review the possibility of overtreating some patients with LARC.