Significance of extranodal tumour deposits in colorectal cancer: A systematic review and meta-analysis

Aims: The presence and significance of extranodal tumour deposits (ENTDs) in colorectal cancer (CRC) continue to cause controversy in terms of origin, classification and prognostic significance. This review aims to assess current evidence on the origin of ENTDs in CRC and their effect on overall and disease-free survival. Methods: A systematic review and meta-analysis were carried out in accordance with the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. End-points included prevalence of ENTDs, relationship with extramural venous invasion (EMVI), overall survival (OS) and disease-free survival (DFS). Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated using Stata software. Results: Twenty-six studies comprising 19,980 patients were included. The prevalence of ENTDs ranged from 10.2% to 44.2% (median 21.3%). There was a significantly increased odds of having ENTD if EMVI was present with a pooled OR of 2.51 (95% CI 2.27-2.77) p <= 0.001. The pooled HR for adverse OS in patients with ENTD was 1.63 (95% CI 1.44 -1.61), p <= 0.001. For adverse DFS the pooled HR was 1.77 (95% CI 1.37-2.11), p <= 0.001. Conclusion: This meta-analysis confirms the negative impact of ENTDs on OS and DFS despite variations in classification and prevalence. ENTDs are significantly associated with EMVI. The prognostic implications of ENTDs are not sufficiently recognised in current staging systems. TNM 8 has failed to address this and has not made use of the available evidence to determine the correct position of ENTDs according to their prognostic effect. The prognostic hierarchy should be N0, N1, N2 with N1c being the most severe. Additionally the exclusion of lesions of vascular, lymphatic and perineural origin by TNM 8 has no evidence base. (C) 2017 Elsevier Ltd. All rights reserved.