Retrospective Cohort Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Apr 15, 2019; 11(4): 295-309
Published online Apr 15, 2019. doi: 10.4251/wjgo.v11.i4.295
Predictive factors of histological response of colorectal liver metastases after neoadjuvant chemotherapy
Chloé Serayssol, Charlotte Maulat, Florence Breibach, Fatima-Zohra Mokrane, Janick Selves, Rosine Guimbaud, Philippe Otal, Bertrand Suc, Emilie Berard, Fabrice Muscari
Chloé Serayssol, Charlotte Maulat, Bertrand Suc, Fabrice Muscari, Department of Digestive Surgery and Liver Transplantation, Toulouse-Rangueil University Hospital, Toulouse 31059, France
Florence Breibach, Janick Selves, Department of Pathology, Toulouse University Hospital, Toulouse 31059, France
Fatima-Zohra Mokrane, Philippe Otal, Department of Radiology, Toulouse-Rangueil University Hospital, Toulouse 31059, France
Rosine Guimbaud, Department of Oncology, Toulouse-Rangueil University Hospital, Toulouse 31059, France
Emilie Berard, The Toulouse Research Methodology Support Unit, Toulouse University Hospital, Toulouse 31000, France
Author contributions: Serayssol C, Maulat C, Breibach F, Berard E and Muscari F performed the research and wrote the paper; Mokrane FZ, Selves J, Guimbaud R, Otal P and Suc B provided critical revision of the manuscript for important intellectual content.
Institutional review board statement: This study was reviewed and approved by the Toulouse University Hospital Review Board.
Informed consent statement: Patients were not required to give informed consent to the study because the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent.
Conflict-of-interest statement: All authors declare no conflicts-of-interest related to this article.
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: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Charlotte Maulat, Academic Fellow, Department of Digestive Surgery and Liver Transplantation, Toulouse-Rangueil University Hospital, CHU Rangueil, 1 avenue J Poulhès, Toulouse 31059, France. charlotte.maulat@gmail.com
Telephone: +33-561322741 Fax: +33-561322936
Received: October 2, 2018
Peer-review started: October 2, 2018
First decision: October 25, 2018
Revised: November 27, 2018
Accepted: December 31, 2018
Article in press: January 1, 2019
Published online: April 15, 2019
Processing time: 196 Days and 12.9 Hours
ARTICLE HIGHLIGHTS
Research background

Colorectal cancer is the third most common cancer in men and the second most common in women worldwide. Almost a third of the patients has or will develop liver metastases. Neoadjuvant chemotherapy (NAC) has recently become nearly systematic prior to surgery of colorectal livers metastases (CRLMs). The response to NAC is evaluated by radiological imaging according to morphological criteria. More recently, the response to NAC has been evaluated based on histological criteria of the resected specimen. The most often used score is the tumor regression grade (TRG), which considers the necrosis, fibrosis, and number of viable tumor cells.

Research motivation

Few studies to date have documented the influence of TRG on patient survival, and they were mostly published by the authors of the scoring systems. This explains why the histological regression score of CRLM specimens is rarely used in current practice[15,32]. Therefore, at present, analysis of the histological response by the TRG has no influence on whether or not adjuvant chemotherapy is administered. To our knowledge, no study has attempted to identify the predictive factors of histological response after NAC.

Research objectives

Our research aimed to analyze the histological response, according to the Rubbia-Brandt TRG, on CRLM surgery performed after NAC. It also sought to identify independent predictive factors of a good response, and to analyze the influence of this response on overall and disease-free survival.

Research methods

From January 2006 to December 2013, 150 patients who had undergone surgery for CRLMs after NAC were included. The patients were separated into two groups based on their histological response, according to Rubbia-Brandt TRG. Based on their TRG, each patient was either assigned to the responder (R) group (TRG 1, 2, and 3) or to the non-responder (NR) group (TRG 4 and 5). All of the histology slides were re-evaluated in a blind manner by the same specialized pathologist. Univariate and multivariate analyses were performed.

Research results

Seventy-four patients were classified as responders and 76 as non-responders. The postoperative mortality rate was 0.7%, with a complication rate of 38%. Multivariate analysis identified five predictive factors of histological response. Three were predictive of non-response (NR): More than seven NAC sessions, absence of a radiological response after NAC, and repeat hepatectomy (P < 0.005). Two were predictive of a good response (R): Rectal origin of the primary tumor and a liver-first strategy (P < 0.005). The overall survival was 57% at 3 yr and 36% at 5 yr. The disease-free survival rates were 14% at 3 yr and 11% at 5 yr. Factors contributing to a poor prognosis for the DFS were: No histological response after NAC, largest metastasis > 3 cm, more than three preoperative metastases, R1 resection, and the use of a targeted therapy with NAC (P < 0.005).

Research conclusions

The histological response of CRLMs after NAC has an influence on survival, hence warranting consideration. We found, however, that this influence on overall survival was lacking in cases of particularly aggressive disease, with microscopic vascular invasion upon histological analysis.

Research perspectives

Two simple criteria enable the prediction of a histological response after NAC: More than seven treatment sessions and absence of a radiological response.