Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases

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.