The Potential for Overtreatment with Total Neoadjuvant Therapy (TNT): Consider One Local Therapy Instead

ABSTRACT Purpose of Review With increased therapeutic options in rectal cancer, a central question has become how to tailor therapy to patient preferences to avoid both over and under treatment. Total Neoadjuvant Therapy (TNT), defined as delivering all planned chemotherapy and radiation therapy (RT) before surgery, was developed with the primary goal of improving overall survival through early elimination of micrometastatic disease. In this narrative review assessing patients with operable adenocarcinoma of the rectum, we sought to evaluate TNT versus alternative options with regard to both quality of life (QoL) and oncologic outcomes. Recent Findings Survey data of patient preferences reveal that an increased focus on QoL when discussing options is essential. While evidence favors TNT improving distant metastases-free survival, this has not yet translated to a clear OS benefit. The improved pathologic complete response rate with TNT compared to short course RT or chemoradiation alone suggests proceeding to surgery might result in overtreatment, lending support to a Watch-and-Wait (W&W) option for patients with a goal for non-operative management (NOM) if a clinical complete response (cCR) is achieved. Similarly, for select low-risk patients, surgery may be the only local therapy required allowing for safe omission of RT. Conclusions In the treatment of rectal cancer, the future appears to be moving towards one local therapy. As an alternative to TNT, there is growing support for the concept we define herein as total definitive therapy (TDT) instead: chemoradiation followed by consolidation chemotherapy, saving surgery only for incomplete responders rather than as part of the initial treatment plan. Also, selective use of RT should be considered for low-risk patients. By thoroughly assessing how these treatment de-escalation options compare to more traditional treatment algorithms, this narrative review provides guidance on how to honor patient preferences for QoL by avoiding treatments that might offer negligible benefits in oncologic outcomes.