Towards precision medicine in colorectal cancer liver metastases.

Abstract

Colorectal cancer (CRC) is a prevalent disease globally; it is the third leading cause in cancer incidence and the second cause of cancer-related death worldwide [1]. According to the data published by GLOBOCAN 2018 CRC incidence rates in developed countries are approximately threefold higher than in transitioning countries; however, CRC related mortality rates do not differ significantly due to the fact that average case fatality is higher in lower human developments index settings. Liver is the most common site of metastasis from colorectal cancers (50–60% of the cases). Close to a third of patients have liver metastases either at the time of diagnosis (synchronous in 1/3 of cases) or during the disease course (metachronous in 2/3 of cases) [2]. The approach to the treatment of liver metastases from CRC includes surgical resection, in various modalities, some examples are one-stage hepatectomy, two-stage hepatectomy (TSH) with portal vein ligation or embolization, TSH with associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) [3] or ultrasound guided one stage hepatectomy associated with or without ablating methods such as radiofrequency ablation or microwave ablation [4] and systemic treatment, with different chemotherapy protocols in combination with biological agents, such as antiangiogenic therapy or I-EGFR (panitumumab or cetuximab). The strategic alliance between the surgical oncologist and the medical oncologist has been defined through the International Consensus Meeting (Expert Group on OncoSurgery management of Liver Metastases) published in 2012 [5]. One of the most important issues is to define the resectability criteria, which have varied over time as well as the timing of chemotherapy, either neoadjuvant, perioperative or postresection of metastases, with a pseudoadjuvant criteria. The most important issue in almost all cases is multidisciplinary work to guarantee the best therapeutic results and survival benefits for the individual patient. Specialized hospitals with multidisciplinary tumor boards including radiologists, pathologists, oncologists and liver surgeons show better resectability and survival rates than general hospitals or nonspecialized centers. Five year survival has increased from less than 8%, with palliative chemotherapy, to 25–40% using multimodal management including chemotherapy and surgical procedures [6]. On the other hand, resectability criteria have been defined on the basis of technical and oncologic data, the latter according to the presence or lack of extrahepatic disease and progression of disease after systemic treatment, both variables are associated with poor prognosis [7]. There is growing interest in directly assessing tumor biology by molecular profiling and integrating biomarkers into prognostication systems [8]. The KRAS gene has been extensively studied, as there was found to be a high concordance of KRAS status between primary CRC and colorectal liver metastases, this biomarker can be evaluated upon biopsy or resected specimens from the primary tumor [9]. The most recent publications of new and more effective chemotherapies and novel surgical techniques developed in recent years have increased the number of resectable patients with colorectal liver metastases [10]. The caveat of