Prognostic impact and implications of extracapsular lymph node involvement in colorectal cancer: A systematic review with meta-analysis

N. Veronese, A. Nottegar, A. Pea, M. Solmi, B. Stubbs, P. Capelli, G. Sergi, E. Manzato, M. Fassan, L. D. Wood, A. Scarpa, Claudio Luchini

Research output: Contribution to journalReview articlepeer-review

50 Scopus citations


Background: The extranodal extension (ENE) of nodal metastasis (i.e. the extension of tumor cells through the nodal capsule into the perinodal adipose tissue) has recently emerged as an important prognostic factor in different types of malignancies. However, the tumor-node-metastasis (TNM) staging system for colorectal cancer does not consider it as a prognostic parameter. Therefore, we conducted a systematic review and meta-analysis to determine the prognostic role of ENE in patients with lymph node-positive colorectal cancer. Materials and methods: Two independent authors searched PubMed and SCOPUS until 7 January 2015 without language restrictions. Prospective studies reporting data on prognostic parameters in subjects with colorectal cancer, comparing participants with the presence of ENE (ENE+) versus only intranodal extension (ENE-) were eligible. Data were summarized using risk ratios (RRs) for the number of deaths/recurrences and hazard ratios (HRs) together with 95% confidence intervals (CIs) for time-dependent risk related to ENE+, adjusted for potential confounders. Results: Thirteen studies including 1336 patients were identified with a median follow-up of 4.7 years. ENE was associated with a higher T stage and tumor grading. In addition, ENE was associated with a significantly increased risk of allcause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I2 = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I2 = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I2 = 47%; HR = 2.31, 95% CI 1.54- 3.44, P < 0.0001, I2 = 48%).

Original languageEnglish (US)
Pages (from-to)42-48
Number of pages7
JournalAnnals of Oncology
Issue number1
StatePublished - Jan 1 2016


  • As well as in future oncologic staging systems
  • Based of these results
  • Ene should be considered from the gross sampling to the pathology report
  • In colorectal cancer

ASJC Scopus subject areas

  • Hematology
  • Oncology


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