Total Neoadjuvant Therapy for High Risk Rectal Cancer in Western and Asian Populations - Current Evidence and Clinical Applications.

Recent data from several randomized controlled trials (RCTs) have shown that Total Neoadjuvant Therapy (TNT) can improve the treatment outcome of patients with high-risk rectal cancer from Western and East Asian populations. Systemic intensification with chemotherapy administered before (induction) or after (consolidation) neoadjuvant radiotherapy (RT) prior to total mesorectal excision (TME) surgery has been shown to improve disease-free survival (DFS), pathologic complete response (pCR) rate, treatment compliance and/or reduce the risk of disease-related treatment failure for high-risk rectal cancer. In this review we highlighted the key results of RCTs on different TNT approaches conducted in Western and Asian populations, and their impact on clinical practice and research direction. We discussed the salient issues and controversies arising from these studies such as the optimal duration of TNT, factors affecting patient selection and the feasibility of adopting a watch-and-wait approach in complete responders to TNT. There are considerable variations between treatment guidelines from Western and East Asian regions on adopting TNT in the management of high-risk rectal cancer, therefore reflecting regional differences in oncologist's preferences and feasibility in implementing TNT. The review concluded by providing an update on some of the key ongoing RCTs into a risk-adapted approach to incorporating TNT in clinical practice, and also translational research into predictive and prognostic biomarkers of response to TNT for high risk rectal cancer.