Key clinical considerations in selecting total neoadjuvant therapy for locally advanced rectal cancer

Total neoadjuvant therapy (TNT) is gaining favour as the preferred treatment approach for all locally advanced rectal cancer (LARC). The evidence landscape for TNT is supported by multiple trials that show a reduction in distant metastases and more recently an overall survival benefit. However, LARC as a term includes a heterogenous patient population. There are also several different schedules of radiotherapy and chemotherapy that fall under the umbrella term of TNT. The role of watch and wait strategies after TNT is an evolving option that can improve long term functional outcomes for a subgroup of patients. These developments together have resulted in a complex clinical and evidence landscape with different endpoints that need attention when selecting a neoadjuvant treatment strategy.

Three broad considerations are discussed in this commentary. Firstly, tumour characteristics and MRI-based risk stratification relevant to a summary of oncological outcomes, including impact on rates of local control, development of distant metastases, survival and relevant functional outcomes after TNT is presented. Secondly, the value placed by the patient on non-operative management. The evidence supporting watch and wait after TNT and the limitations of such an approach is summarised with helpful infographics to support shared decision making in clinic. Finally, patient specific factors such as comorbidity are detailed.

This commentary aims to serve as a nuanced map that describes how the current landscape of TNT strategies can be applied to an individual patient. In conclusion, the anticipated near-future developments in TNT are also highlighted.