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

Histol Histopathol. 2021 Feb;36(2):159-181. doi: 10.14670/HH-18-274. Epub 2020 Nov 9.


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.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Cell Differentiation
  • Colorectal Neoplasms / diagnosis*
  • Colorectal Neoplasms / pathology*
  • Disease-Free Survival
  • Histological Techniques
  • Humans
  • Inflammation
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / secondary*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Observational Studies as Topic
  • Portal Vein / pathology
  • Prognosis
  • Risk

Grant support