Can molecular biomarkers replace a clinical risk score for resectable colorectal liver metastasis?

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.

Genetic And Morphological Evaluation (GAME) score for patients with colorectal liver metastases

“…Importantly, GAME is the first clinical risk score to incorporate clinically available genetic information ( KRAS status). Previous scores have been criticized for their reliance on traditional clinicopathological variables, at a time when the importance of tumour biology is increasingly being recognized. Although the prognostic impact of many genetic markers has been evaluated, KRAS remains the most commonly used owing to its wide availability and robust association with outcomes.…”

Mini-invasive vs open resection of colorectal cancer and liver metastases: A meta-analysis

“…The liver is the most common organ for metastasis from colorectal neoplasms. Approximately 40% of patients with CRC eventually develop liver metastases, and 15%-20% of CRC patients have synchronous colorectal liver metastases (SCRLM) at the time of initial diagnosis; the metastases are limited to the liver in 70%-80% of these patients, but only a subset of these metastases are resectable[2-4]. Complete radical resection of primary and metastatic lesions is a potential curative treatment strategy for patients with resectable CRC and SCRLM, which is directly related to the prognosis of these patients[5,6].…”

Analysis of Response Evaluation Criteria in Solid Tumors reduction ratio of primary chemotherapy in unresectable advanced or recurrent colorectal cancer

“…3). As 70–87% of patients with unresectable or recurrent CRC harbored liver metastases (32,33,35–38), the RR reported in clinical trials for unresectable or recurrent CRC mostly reflected the LRR.…”