Liver steatosis and fibrosis as independent prognostic factors affecting survival in colorectal cancer with liver metastases.

Abstract

165 Background: Colorectal cancer is one of the leading causes of cancer-related death, and the liver represents the most common site of metastases. Greater depth of tissue invasion and lymph node metastases (more advanced T and N stage) are associated with increased risk of liver metastases, but how co-pathologies of the liver associate with disease progression and survival are not known. Further, prognostic factors associated with overall survival in patients with colorectal liver metastases (CRLM) remain poorly understood. Clinical factors affecting liver morphology and biomechanical properties, such as preexisting fibrosis or steatosis, may impact the pathogenesis of CRLM and thus the clinical prognosis. Current literature is mixed about whether prior steatosis and fibrosis contribute significantly to CRLM pathogenesis and prognosis. The purpose of this study is to evaluate whether liver steatosis and fibrosis impact outcomes in patients with CRLM. Methods: All CLRM cases (n = 197) that underwent resection between 2003 and 2007 from The Cancer Imaging Archive were included in our study cohort. For each clinical covariate, we generated a univariate model for overall survival and those meeting a modest predictive threshold (p < 0.15) were included in a multivariable model. These included: presence of major comorbidity, chemotherapy preceding resection of liver metastases, clinical risk score, presence of extrahepatic disease at time of diagnosis, presence of steatosis on CT imaging, percentage of residual tumor after treatment, and presence of fibrosis on CT. All statistics were performed in R (v.2022.12.0). Results: A multivariable Cox proportional hazards model identified four statistically significant clinical factors predictive of overall survival: clinical risk score (HR = 1.60, p = 0.026), presence of extrahepatic disease (HR = 2.33, p = 0.027), presence of steatosis (HR = 0.51, p = 0.0057), and fibrotic proportion of liver tissue less than 40% (HR = 2.63, p = 0.033). There were also four statistically significant clinical factors predictive of disease-free survival in the liver: chemotherapy preceding resection of liver metastases (HR = 2.28, p = 0.0011), presence of extrahepatic disease (HR = 2.18, p = 0.024), presence of steatosis (HR = 0.49, p = 0.0030), and fibrotic proportion of liver tissue less than 40% (HR = 2.74, p = 0.016). Conclusions: Our findings suggest that increased steatosis and fibrosis, as assessed by CT scans, are paradoxically protective in CRLM, showing longer disease-free survival and overall survival rates. We hypothesize that liver fibrosis and steatosis impact the microenvironment of the neoplastic cells in the liver, impairing tumor progression in this milieu. Further research is needed to assess how non-neoplastic co-pathologies resulting in biophysical changes affect tumor growth and overall survival.