Histopathological prognostic factors for colorectal liver metastases: A systematic review and meta-analysis of observational studies.

INTRODUCTION Resection is the mainstay of treatment for colorectal liver metastases (CRLMs). Many different histopathological factors related to the primary colorectal tumour have been well studied; however, histopathological prognostic factors related to CRLMs are still under evaluation. OBJECTIVE To identify histopathological factors related to overall survival (OS) and disease-free survival (DFS) in patients with resected CRLMs. METHODS A systematic review was performed with the following databases up to August 2020: PubMed, EMBASE, Web of Science, SciELO, and LILACS. The GRADE approach was used to rate the overall certainty of evidence by outcome. RESULTS Thirty-three studies including 4,641 patients were eligible. We found very low certainty evidence that the following histopathological prognostic factors are associated with a statistically significant decrease in OS: presence of portal vein invasion (HR, 0,50 [95% CI, 0,37 to 0,68]; I²=0%), presence of perineural invasion (HR, 0,55 [95% CI, 0,36 to 0,83]; I²=0%), absence of pseudocapsule (HR, 0,41 [CI 95%, 0,29 to 0,57], p<0,00001; I²=0%), presence of satellite nodules (OR, 0,45 [95% CI, 0,26 to 0,80]; I²=0%), and the absence of peritumoural inflammatory infiltrate (OR, 0,20 [95% CI, 0,08 to 0,54]; I²=0%). Outcome data on DFS were scarce, except for tumour borders, which did not present a significant impact, precluding the meta-analysis. CONCLUSION Of the histopathological prognostic factors studied, low- to moderate-certainty evidence shows that vascular invasion, perineural invasion, absence of pseudocapsule, presence of satellite nodules, and absence of peritumoral inflammatory infiltrate are associated with shorter overall survival in CRLMs.