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

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. 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 option for patients with a goal for nonoperative management if a clinical complete response is achieved. Similarly, for select low-risk patients, surgery may be the only local therapy required allowing for safe omission of RT. In the treatment of rectal cancer, the future appears to be moving toward one local therapy. As an alternative to TNT, there is growing support for the concept we define herein as total definitive therapy 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. (C) 2021 Elsevier Inc. All rights reserved.

Automated summary

This narrative review evaluates the differences between Total Neoadjuvant Therapy (TNT) and alternative options in terms of quality of life (QoL) and oncologic outcomes for patients with rectal cancer. Survey data highlight the importance of considering QoL when discussing treatment options. While evidence supports TNT in improving distant metastases-free survival, the overall survival benefit is still unclear. The higher pathologic complete response rate with TNT suggests the potential for overtreatment with surgery, supporting a watch-and-wait approach. For low-risk patients, surgery may not be necessary, and radiation therapy can be omitted. Therefore, this review provides guidance on honoring patient preferences for QoL by avoiding treatments with negligible benefits in oncologic outcomes.