Total neoadjuvant treatment, non-operative management and radiotherapy-free strategies: New approaches for the management of proficient mismatch repair/microsatellite stable locally advanced rectal cancer. A narrative review and evidence-based algorithm

In recent years, new therapeutic approaches have emerged in addition to classical neoadjuvant (chemo)radiotherapy for the treatment of locally advanced rectal cancer (LARC): total neoadjuvant treatment, non-operative management, and radiotherapy-free strategy. While the introduction of these approaches in a relatively short timeframe has quickly increased our therapeutic armamentarium, on the other hand it has complicated the decision-making process regarding the choice of the most appropriate treatment strategy for each patient with LARC. Therefore, a tool to interpret the evidence from clinical trials and to translate them into daily practice is highly demanded. In the present review, we address how these new developments are changing the multimodal treatment of LARC and offer an algorithm to integrate them into clinical practice.