Editorial
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2017; 9(3): 98-104
Published online Mar 15, 2017. doi: 10.4251/wjgo.v9.i3.98
Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?
Torhild Veen, Kjetil Søreide
Torhild Veen, Kjetil Søreide, Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, N-4068 Stavanger, Norway
Kjetil Søreide, Gastrointestinal Translational Research Unit, Molecular Laboratory, Stavanger University Hospital, N-4068 Stavanger, Norway
Kjetil Søreide, Department of Clinical Medicine, University of Bergen, N-5020 Bergen, Norway
Author contributions: Søreide K planned the editorial; both Veen T and Søreide K searched the literature, drafted the paper, contributed to rounds of revisons and, approved the final version for submisssion.
Conflict-of-interest statement: None declared.
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/
Correspondence to: Kjetil Søreide, MD, PhD, Professor, Consultant Surgeon, Department of Gastrointestinal Surgery, HPB Unit, Stavanger University Hospital, P.O. Box 8100, N-4068 Stavanger, Norway. ksoreide@mac.com
Telephone: +47-515158330 Fax: +47-51519919
Received: October 7, 2016
Peer-review started: October 8, 2016
First decision: November 11, 2016
Revised: November 25, 2016
Accepted: December 27, 2016
Article in press: December 29, 2016
Published online: March 15, 2017
Abstract

In resectable colorectal liver metastasis (CRLM) the role and use of molecular biomarkers is still controversial. Several biomarkers have been linked to clinical outcomes in CRLM, but none have so far become routine for clinical decision making. For several reasons, the clinical risk score appears to no longer hold the same predictive value. Some of the reasons include the ever expanding indications for liver resection, which now increasingly tend to involve extrahepatic disease, such as lung metastases (both resectable and non-resectable) and the shift in indication from “what is taken out” (e.g., how much liver has to be resected) to “what is left behind” (that is, how much functional liver tissue the patient has after resection). The latter is amenable to modifications by using adjunct techniques of portal vein embolization and the associating liver partition and portal vein ligation for staged hepatectomy techniques to expand indications for liver resection. Added to this complexity is the increasing number of molecular markers, which appear to hold important prognostic and predictive information, for which some will be discussed here. Beyond characteristics of tissue-based genomic profiles will be liquid biopsies derived from circulating tumor cells and cell-free circulating tumor DNA in the blood. These markers are present in the peripheral circulation in the majority of patients with metastatic cancer disease. Circulating biomarkers may represent more readily available methods to monitor, characterize and predict cancer biology with future implications for cancer care.

Keywords: Colorectal cancer, Liver metastasis, KRAS, Disease-free survival, Circulating tumor cell, Liver surgery, Overall survival, Molecular biomarkers

Core tip: As a general rule, “good” colorectal liver metastasis (CRLM) cases amenable for surgery have fewer bad genetic traits, such as less likelihood for BRAF mutations or KRAS mutations. KRAS mutation in patients with resectable CRLM suggests a more aggressive disease with shorter progression free and overall survival. Emerging evidence suggest that tumors change during the course of treatment and, thus giving way to new clones that may be of a different genetic makeup and have a different resistance pattern. Thus, new ways of monitoring disease and markers of progression is needed, including circulating cancer biomarkers and tissue-based genetic profiles.