Connecting the dots: a multidisciplinary approach to optimize rectal cancer treatment outcomes

Abstract

The treatment of advanced rectal cancer has been subjected to many changes in recent years. Diagnostics has improved and the number of treatment options has been expanded. The current neoadjuvant treatment consists of chemoradiotherapy. This results in a complete response in 15-27% of patients. A complete response supports rectal-sparing treatment strategies, such as active surveillance (also called watch-and-wait), or local excision. This can avert surgery-related morbidity (and associated deterioration in quality of life) and is therefore increasingly offered to patients. This thesis investigates whether and how adjusted neoadjuvant treatment results in a more complete response. A meta-analysis shows that more intensive neoadjuvant treatments do not result in better response or survival. In addition, intensive therapy is associated with more toxicity and reduced quality of life. The lack of response improvement may be a result of inadequate patient selection. It is therefore important to identify factors that can predict the effectiveness of a new treatment. This thesis investigated the predictive value of tumor-infiltrating lymphocytes in biopsies for complete response, but evidence for clinical applicability is lacking. Elderly or vulnerable patients might require less intensive neoadjuvant treatment. This thesis showed that this results in lower complete response rates. Hence, less intensive treatment has little rectal-sparing potential. However, it is safe: both radiotherapy and surgical side effects are acceptable. Based on this thesis, modification of the neoadjuvant treatment is not recommended. Multidisciplinary collaborations are needed for the identification and optimization of treatments that improve response while maintaining quality of life.