Tumor Regression Grade (TRG) in rectal adenocarcinoma: an overview of scoring systems and inter-pathologist agreement

The current therapeutic strategy for the treatment of stage II or III rectal adenocarcinomas includes the combination of chemoradiotherapy followed by surgery. This kind of treatment showed an increase in OS, in DFS, and in sphincter-sparing procedure rates. The modifications induced by neoadjuvant therapy on the tumor bed can be evaluated by applying pathological tumor regression scoring (TRG) systems, whose aim is to quantify and evaluate the extension of regressive modifications after treatment. Several classification methods have been built and included in clinical practice. It is possible to recognize two main approaches to characterize the pathological response: (i) valuation of the amount of therapy-induced fibrosis compared with the residual tumor; and (ii) estimation of the percentage of residual tumor related to the size of the former tumoral bed. The primary aim of the TRG system is to allow a prognostic stratification of tumors, identifying the best adjuvant treatment for the patients, even if there are several studies whose results conflict about the TRG prognostic impact. There is no widely accepted/applied TRG system in the clinical practice. This study aimed to describe the most used TRG scoring systems and identify their interobserver agreement and reproducibility in a large series of rectal adenocarcinomas treated with a combination of chemoradiotherapy and immunotherapy (the AVANA protocol; chemoradiotherapy plus avelumab in patients with locally advanced rectal cancer).