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World J Gastroenterol. Apr 21, 2016; 22(15): 3937-3944
Published online Apr 21, 2016. doi: 10.3748/wjg.v22.i15.3937
Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases
Valerio Lucidi, Alain Hendlisz, Jean-Luc Van Laethem, Vincent Donckier
Valerio Lucidi, Department of Abdominal Surgery, Hôpital Erasme, Centre de Chirurgie Hépato-Biliaire de l’ULB, Université Libre de Bruxelles, 1070 Brussels, Belgium
Alain Hendlisz, Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles, 1000 Brussels, Belgium
Jean-Luc Van Laethem, Department of Gastroenterology, Hôpital Erasme, Université Libre de Bruxelles, 1070 Brussels, Belgium
Vincent Donckier, Department of Surgery, Institut Jules Bordet, Department of Abdominal Surgery, Hôpital Erasme, Centre de Chirurgie Hépato-Biliaire de l’ULB, Université Libre de Bruxelles, 1000 Brussels, Belgium
Author contributions: Lucidi V, Hendlisz A, Van Laethem JL and Donckier V wrote the paper.
Conflict-of-interest statement: Authors declare no conflict of interests for 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/
Correspondence to: Vincent Donckier, MD, PhD, Professor of Surgery, Institut Jules Bordet, Department of Abdominal Surgery, Hôpital Erasme, Centre de Chirurgie Hépato-Biliaire de l’ULB, Université Libre de Bruxelles, Rue Héger-Bordet, 1, 1000 Brussels, Belgium. vincent.donckier@erasme.ulb.ac.be
Telephone: +32-2-5413158 Fax: +32-2-5413141
Received: December 29, 2015
Peer-review started: December 30, 2015
First decision: January 28, 2016
Revised: February 15, 2016
Accepted: March 18, 2016
Article in press: March 18, 2016
Published online: April 21, 2016
Processing time: 96 Days and 18.5 Hours
Abstract

In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.

Keywords: Colorectal; Liver; Metastases, Surgery; Chemotherapy; Missing

Core tip: Surgery is considered as the only potentially curative option for patients with colorectal liver metastases, while chemotherapy alone is considered as a palliative treatment. Recent data shown that colorectal liver metastases disappearing after chemotherapy, so-called missing metastases, could not reappear on the long-term, suggesting that systemic treatments might be curative in selected cases. Accordingly, we propose that classical recommendation to limit surgery only when all initial tumor sites could be resected might have become partially obsolete. Furthermore, when missing liver metastases have been induced, adjuvant surgery targeting the resistant part of the disease could represent a new strategy.