Surgery for colorectal liver metastases: The evolution of determining prognosis

Abstract

Despite improvements in the multi-modality treatment of colorectal liver metastasis (CRLM), survival after resection remains varied. Determining prognosis after surgical resection has historically been predicated on preoperative clinicopathological factors such as primary tumor stage, carcinoembryonic antigen levels, number of liver metastases, presence of extrahepatic disease, as well as other factors. While scoring systems have been developed by combining certain preoperative factors, these have been inconsistent in accurately determining prognosis. There has been increasing interest in the use of biologic and molecular markers to predict prognosis following CRLM. The role of markers such as KRAS, BRAF, p53, human telomerase reverse transcriptase, thymidylate synthase, Ki-67, and hypoxia inducible factor-1α and their correlation with accurately predicting survival after surgical resection have been supported by several studies. Furthermore, other elements such as pathological response to chemotherapy and the presence of circulating tumor cells have shown promise in accurately determining prognosis after resection for colorectal liver metastasis. We herein review past, present, and possible future markers of prognosis among colorectal cancer patients with liver metastasis undergoing resection with curative intent.

Keywords: Colorectal; Metastasis; Molecular markers; Outcomes; Prognosis; Risk score.

Figure 1

Survival after hepatic resection stratified by the clinical risk score. Open box: score 0 (n = 52); filled triangle: score 1 (n = 262); open circle: score 2 (n = 350); filled circle: score 3 (n = 243); filled box: score 4 (n = 80); open triangle: score 5 (n = 14). P < 0.0001 (from Fong et al[9]). Used with permission.

Figure 2

Disease specific survival after liver resection stratified by KRAS mutation (from Nash et al[110]). Used with permission.

Figure 3

Overall (A) and disease-free (B) survival after hepatic surgery for colorectal liver metastasis depicted by KRAS mutation status (multivariate Cox model) (wtKRAS, wild type KRAS; mKRAS, mutated KRAS) (from Karagkounis et al[111]). Used with permission.

Figure 4

Patients with detectable ctDNA following resection of colorectal liver metastasis, recurrence was universal. A: Depiction of process by which ctDNA is detected and amplified from the specimen and plasma of patients; B: Representative flow cytometric data of ctDNA of one subject who underwent resection of colorectal liver metastasis. Note that the notable difference in recurrence-free survival in subjects with detectable vs undetectable ctDNA (from Diehl et al[141]). Used with permission. PCR: Polymerase chain reaction.

Figure 5

Carcinogenesis of colorectal cancer (from Markowitz et al[145]). Used with permission. EGFR: Epidermal growth factor receptor; TGF: Transforming growth factor; COX-2: Cyclooxygenase-2.