Total neoadjuvant therapy in rectal cancer: the evidence and expectations

Current management of locally advanced rectal cancer achieves high cure rates, distant metastatic spread being the main cause of patients' death. Total neoadjuvant therapy (TNT) employs (chemo)radiotherapy and combined chemotherapy prior to surgery to improve the treatment outcomes. TNT has been shown to reduce significantly distant metastases, increase disease-free survival by 5 – 10% in 3 years, and finally also overall survival (≈ 5% in 7 years). It proved to double the rate of pathologic complete responses, making it an attractive strategy for non-operative management to avoid permanent colostomy in patients with distal tumors. In addition, it endorses adherence to the therapy due to better tolerance and, potentially, shortens its overall duration. A number of questions related to TNT remain currently unresolved including the indications, preferred radiotherapy and chemotherapy regimens, their sequence, timing of surgery, and role of adjuvant therapy. A stratified approach may be the optimal way to go. • Total neoadjuvant therapy involves radiotherapy and chemotherapy prior to surgery. • TNT is a novel strategy in the management of locally advanced rectal cancer. • It can significantly reduce the distant metastatic spread and increase DFS and OS. • It has been shown to double the rate of pCR, enabling the non-operative management. • A number of issues are still unresolved; a risk-based approach may be required.