Prediction of hepatic metastasis and relapse in colorectal cancers based on concordance analyses with liver fibrosis scores

Xiang Hu, Audrey Marietta, Wei‐Xing Dai, Ya‐Qi Li, Xiao‐ji Ma, Long Zhang, San‐Jun Cai, Jun‐Jie Peng

Liver fibrosis, resulted from several liver diseases, are increasing up to 25% in population in global. It remains undetermined how much impact liver fibrosis have on the development of hepatic metastasis and relapse in colorectal cancer (CRC). Hence the aim of this study was to clarify the role of liver fibrosis on hepatic metastasis and relapse in CRC undergoing curative therapy. We enrolled consecutive 1652 patients with radical colorectal surgery as the discovery cohort, and the validation set enrolled 432 CRC patients with hepatic metastasis. To determine liver fibrosis, the NFS, FIB4 and APRI scores were applied. The influence of liver fibrosis on hepatic metastasis and relapse was assessed by survival analyses. Nomograms with fibrosis score incorporated were established to identify the incremental value for individualized relapse estimation, which was then assessed with respect to calibration, discrimination, and clinical usefulness. The high liver fibrosis score patients had significantly worse outcomes than low score in 5-year hepatic metastasis (22.6 vs. 8.7%) in discovery cohort, and relapse (58.2 vs. 44.1%) in validation cohort. Multivariate analysis also revealed liver fibrosis as an independent prognostic factor. The distribution analysis also demonstrated higher liver fibrosis score a powerful prognostic factor for hepatic metastasis and relapse. The nomogram incorporated with liver fibrosis score resulted in better performance than TNM staging system and clinicopathologic nomograms. Importantly, the discriminatory capacity of the fibrosis score was superior to that of the CRS score in predicting hepatic specific disease-free survival (DFS) and relapse-free survival (RFS), as demonstrated by the C-index and AUC. The concordance study showed well agreement among NFS, FIB4 and APRI in predicting DFS and RFS. Among these three noninvasive liver fibrosis scores, NFS score performed the best in predicting hepatic specific DFS and RFS. The liver fibrosis was a powerful predictor of hepatic specific DFS and RFS in CRC. Fibrosis niche may be a favorable microenvironment for metastatic formation in the liver.