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


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 all-cause mortality (RR = 1.75; 95% CI 1.42-2.16, P < 0.0001, I(2) = 60%; HR = 1.69, 95% CI 1.32-2.17, P < 0.0001, I(2) = 46%) and of recurrence of disease (RR = 2.07, 95% CI 1.65-2.61, P < 0.0001, I(2) = 47%; HR = 2.31, 95% CI 1.54-3.44, P < 0.0001, I(2) = 48%).


CONCLUSIONS
Based of these results, in colorectal cancer, ENE should be considered from the gross sampling to the pathology report, as well as in future oncologic staging systems.
Department of Medicine, DIMED, University of Padua, Padua.
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Veronese
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
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Nottegar
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, USA.
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Pea
Department of Neuroscience, University of Padua, Padua, Italy.
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Solmi
Health Service and Population Research Department, King's College London, London, UK.
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Stubbs
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
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Capelli
Department of Medicine, DIMED, University of Padua, Padua.
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Sergi
Department of Medicine, DIMED, University of Padua, Padua.
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Manzato
Department of Medicine, DIMED, University of Padua, Padua.
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Fassan
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, USA.
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Wood
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy ARC-NET Research Center, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
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Scarpa
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy ARC-NET Research Center, Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy claudio.luchini@katamail.com claudio.luchini@univr.it.
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Luchini
D015179:Colorectal Neoplasms / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D012044:Regression Analysis; D016896:Treatment Outcome
colon cancer; extracapsular extension; extranodal extension; lymph node metastasis; rectal cancer