Multidisciplinary approach of colorectal liver metastases

Abstract

Colorectal cancer (CRC) is the second most common cause of cancer death in Spain. Fifty percent of patients will develop colorectal liver metastases (CLM) during the course of the disease. Less than 20% of patients with CLM are initially resectable and for them 5-year disease-free survival (DFS) is about 20-25%, with a high recurrence rate. CLM is a heterogeneous disease. From a clinical point of view, four main groups can be differentiated: initially resectable, not optimally resectable, unresectable that could be resectable and unresectable that never will be likely to be resected. Treatment of CLM must be established, always, in a multidisciplinary team discussion with an analysis of prognostic factors and resectability. For patients with resectable CLM, the EORTC trial 364 demonstrated that chemotherapy plus surgery is better than surgery alone. Consequently most patients should be treated with perioperative chemotherapy based on oxaliplatin, and if resection has been done without chemotherapy, they should receive adjuvant chemotherapy after R0 resection. Based on oncological factors, the 5-year survival rate after resection of CLM ranges from 60% to only 14% with a poor score. If a patient has more than one of the poor prognostic factors he should probably be referred for preoperative (induction) chemotherapy. Only a minority of patients with CLM are amenable to surgery; therefore, efforts have been made to increase the percentage of patients who could be candidates for resection. Studies, mostly retrospective, have confirmed the ability of neoadjuvant chemotherapy (conversion chemotherapy) to render some metastases resectable. The regimens we must use depend on the KRAS mutational status and the toxicity profiles of drugs in the context of each patient. In k-ras mutated tumours we can use bevacizumab combined with standard chemotherapy or concomitant administration of the three active agents (FOLFOXIRI) in suitable patients. In k-ras wild-type patients, the combination of cetuximab and FOLFIRI-FOLFOX improved response rates and resection rate in phase III-II trials. With a lower level of evidence, panitumumab is an alternative combined with FOLFOX. Bevacizumab is also an alternative as it does not depend on KRAS status. Radiotherapy is becoming an alternative in selected patients, where surgery is not an alternative. For the majority of patients, who will never be resectable, the continuum of care with chemotherapy will be the paradigm for their management.

MicroRNA-337 inhibits colorectal cancer progression by directly targeting KRAS and suppressing the AKT and ERK pathways

“…Despite advances in the diagnosis and therapy of CRC, which have improved the life expectancy of patients, the prognosis of patients with CRC remains poor (5). Approximately half of CRC patients remarkably develop distant metastases and high rates of recurrence after surgery, which are the main causes of death in the patients (6). Therefore, a better understanding of the molecular mechanisms underlying CRC formation and progression is vital to identify novel diagnostic markers and develop therapeutic strategies for patients with CRC.…”

MicroRNA-375 suppresses human colorectal cancer metastasis by targeting Frizzled 8

“…The five-year survival rate of patients with resectable CRC has recently improved, exceeding 90%, but the survival rate of CRC patients with unresectable metastases remains discouraging at less than 10% [2]. Notably, approximately half of CRC patients develop distant metastases, especially liver metastases, which are the main cause of death in patients [3]. Tumor metastasis is a complex process that consists of multiple sequential steps, including the invasion of cancer cells into surrounding tissues, intravasation, survival in circulation, arrest at distant organ sites, extravasation, and growth in distant organs [4].…”

Increased growth of colorectal liver metastasis following partial hepatectomy

“…When referring to larger CRC metastases, cell-cycle-blocking agents such as ionizing radiation could be considered not only to eliminate the liver metastases themselves, but also to reduce the regenerative response of the surrounding liver mass as a method of pre-treatment prior to liver resection. For example, external-beam and partial liver irradiation may prove promising in this difficult multidisciplinary approach, as the dose of radiation can be adjusted and precisely targeted to parts of the liver [55, 58]. No doubt, future studies will be necessary to clarify the underlying mechanisms, treatment options and understanding of CRC metastatic recurrence in regenerating liver.…”