Systematic Reviews
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2016; 22(37): 8414-8434
Published online Oct 7, 2016. doi: 10.3748/wjg.v22.i37.8414
Defining response to radiotherapy in rectal cancer using magnetic resonance imaging and histopathological scales
Muhammed R S Siddiqui, Jemma Bhoday, Nicholas J Battersby, Manish Chand, Nicholas P West, Al-Mutaz Abulafi, Paris P Tekkis, Gina Brown
Jemma Bhoday, Manish Chand, Al-Mutaz Abulafi, Muhammed RS Siddiqui, Department of Colorectal Surgery, Croydon University Hospital, Croydon, London CR7 7YE, United Kingdom
Jemma Bhoday, Nicholas J Battersby, Gina Brown, Muhammed RS Siddiqui, Department of Radiology, Royal Marsden Hospital, Sutton SM2 5PT, United Kingdom
Nicholas P West, Pathology and Tumour Biology, Leeds Institute of Cancer and Pathology, St. James’s University Hospital, Leeds LS9 7TF, United Kingdom
Paris P Tekkis, Department of Surgery, Royal Marsden Hospital, Fulham Rd, London SM2 5PT, United Kingdom
Author contributions: Siddiqui MRS, Bhoday J and Battersby NJ performed the literature search; Siddiqui MRS and Brown G analysed the data; Chand M wrote and corrected the manuscript; Siddiqui MRS, West NP, Abulafi AM, Tekkis PP and Brown G wrote and corrected the manuscript and approved it for final submission.
Supported by the Royal Marsden Hospital United Kingdom National Institute for Health Research Biomedical Research Centre (to Brown G); and the Yorkshire Cancer Research and Pathological Society of Great Britain and Ireland (to West NP).
Conflict-of-interest statement: None to declare.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Dr. Gina Brown, Consultant Radiologist, Professor, Department of Radiology, Royal Marsden Hospital, Downs Rd, Sutton SM2 5PT, United Kingdom.
Telephone: +44-208-6613156 Fax: +44-208-6439414
Received: March 23, 2016
Peer-review started: March 23, 2016
First decision: May 12, 2016
Revised: July 4, 2016
Accepted: July 31, 2016
Article in press: August 1, 2016
Published online: October 7, 2016

To define good and poor regression using pathology and magnetic resonance imaging (MRI) regression scales after neo-adjuvant chemotherapy for rectal cancer.


A systematic review was performed on all studies up to December 2015, without language restriction, that were identified from MEDLINE, Cochrane Controlled Trials Register (1960-2015), and EMBASE (1991-2015). Searches were performed of article bibliographies and conference abstracts. MeSH and text words used included “tumour regression”, “mrTRG”, “poor response” and “colorectal cancers”. Clinical studies using either MRI or histopathological tumour regression grade (TRG) scales to define good and poor responders were included in relation to outcomes [local recurrence (LR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS)]. There was no age restriction or stage of cancer restriction for patient inclusion. Data were extracted by two authors working independently and using pre-defined outcome measures.


Quantitative data (prevalence) were extracted and analysed according to meta-analytical techniques using comprehensive meta-analysis. Qualitative data (LR, DR, DFS and OS) were presented as ranges. The overall proportion of poor responders after neo-adjuvant chemo-radiotherapy (CRT) was 37.7% (95%CI: 30.1-45.8). There were 19 different reported histopathological scales and one MRI regression scale (mrTRG). Clinical studies used nine and six histopathological scales for poor and good responders, respectively. All studies using MRI to define good and poor response used one scale. The most common histopathological definition for good response was the Mandard grades 1 and 2 or Dworak grades 3 and 4; Mandard 3, 4 and 5 and Dworak 0, 1 and 2 were used for poor response. For histopathological grades, the 5-year outcomes for poor responders were LR 3.4%-4.3%, DR 14.3%-20.3%, DFS 61.7%-68.1% and OS 60.7-69.1. Good pathological response 5-year outcomes were LR 0%-1.8%, DR 0%-11.6%, DFS 78.4%-86.7%, and OS 77.4%-88.2%. A poor response on MRI (mrTRG 4,5) resulted in 5-year LR 4%-29%, DR 9%, DFS 31%-59% and OS 27%-68%. The 5-year outcomes with a good response on MRI (mrTRG 1,2 and 3) were LR 1%-14%, DR 3%, DFS 64%-83% and OS 72%-90%.


For histopathology regression assessment, Mandard 1, 2/Dworak 3, 4 should be used for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5, respectively.

Keywords: Tumour regression, mrTRG, Poor response, Neo-adjuvant therapy, Rectal cancer

Core tip: The degree of primary tumour regression following neo-adjuvant therapy identified on final histopathological specimens is a prognostic factor and response variation has allowed risk stratification, aiding in post-surgical treatment and follow-up decisions. To do this effectively, we need to have a common language for defining good and poor response. Definitions of response using histopathology scales are heterogenous with 19 different scales. There is one pre-operative magnetic resonance imaging (MRI) scale. Outcomes of recurrence and survival histopathology regression assessments should use Mandard 1, 2/Dworak 3, 4 for good response and Mandard 3, 4, 5/Dworak 0, 1, 2 for poor response. MRI indicates good and poor response by mrTRG1-3 and mrTRG4-5, respectively.