Pathological Tumor Regression Grade Classifications in Gastrointestinal Cancers: Role on Patients’ Prognosis

Abstract

Preoperative chemotherapy or combined radiotherapy and chemotherapy (CRT), followed by surgery, represents the standard approach for locally advanced esophageal, gastric, and rectal carcinomas. To adequately evaluate the effects of neoadjuvant CRT in the resection specimens, several histopathologic tumor regression grade (TRG) scoring systems have been introduced into clinical practice. The primary goal of these TRG systems relies on a correct prognostic stratification of patients in the attempt to help clinical decision-making and influence surgical strategies, postoperative adjuvant therapies, and surveillance intensity. However, most TRG systems suffer from poor reproducibility and low interobserver concordance rates. Many efforts have been made in the identification of alternative, robust, simple, and universally accepted TRG scoring systems, which would help in the comparison of different treatment strategies and in the standardization of multimodal therapies. The aim of this review is to analyze the most commonly used TRG systems in gastrointestinal cancers highlighting their pitfalls and usefulness, depending on the tumor type.

Prognostic significance of viable tumor size measurement in hepatocellular carcinomas after preoperative locoregional treatment

“…The extent of residual viable tumor after neoadjuvant treatment is a prognostic factor for various malignant neoplasms, including esophageal, gastric, pancreatic, lung, and colorectal cancers [17][18][19][20][21]. For example, for pancreatic ductal adenocarcinoma, the maximal dimension of the residual tumor is used for assigning the ypT stage according to the TNM system, and although there is still no worldwide consensus on what grading system should be used to evaluate response to neoadjuvant therapy, the degree of tumor response is reported in surgical pathology practice along with the ypT stage [13,22].…”

Comparison of tumor regression grading systems for locally advanced gastric adenocarcinoma after neoadjuvant chemotherapy

“…Although the benefit of this multimodality treatment was first confirmed by the MAGIC trial in 2006, the use of NACT had been adopted in GC for 30 years[ 22 , 23 ]. To assess the treatment response, despite the widespread use of the TRG system for gastrointestinal tract tumors, the response rates are always poor in GC compared with esophageal or colorectal cancer[ 5 ]. This might be due to the lack of chemoradiation and sensitive regimens in preoperative settings.…”

“…The effects of NACT on the tumor can be histopathologically evaluated in subsequent resection specimens by applying pathological tumor regression grading (TRG) systems. There are currently more than five commonly used TRG systems for GC across the world with different principles, different layers, and different cutoff values[ 4 , 5 ]. These various practices in TRG evaluation place a large burden on oncologists and pathologists and make it hard to interpret results from different systems in similar clinical contexts.…”

Precancerous lesions of the stomach, gastric cancer and hereditary gastric cancer syndromes

“…There are many possible reasons which explain the lack of a universally accepted TRG system: 1) absence of standardized different sampling methods which could lead to over-diagnosis of complete pathological tumor regression and this may in part explain its variable prognostic impact. Indeed, the complete microscopic assessment of the entire ulcerated/scarring area should be performed and this is absolutely mandatory if no tumor is identified in the initial blocks; 2) not all classifications take into account the evaluation of response in loco-regional lymph nodes; 3) there is a relatively low concordance rate among pathologists in TRG assignment; 4) systems with a higher number of tiers (more than 4) do not offer any clear cut prognostic advantage 93 .…”