Prognostic impact of extra-nodal extension in thyroid cancer: A meta-analysis.
OBJECTIVE
Lymph node involvement is common in thyroid cancer, but the system of staging does not consider the histological features of lymph node metastases. We conducted a meta-analysis to investigate the prognostic role of extranodal extension (ENE) in thyroid cancer patients.


METHODS
We ran PubMed and SCOPUS searches without language restrictions. Prospective studies reporting data on overall mortality, cancer-specific mortality, or disease recurrence including thyroid cancer patients, in which cases with ENE (ENE+) were compared with those with only intranodal disease (ENE-) were eligible. Data were summarized using risk ratios (RR) for number of deaths/recurrences, and hazard ratios (HR) for time-dependent risks related to ENE+ status, adjusted for potential confounders.


RESULTS
Of 414 hits, 23 studies were eligible and included. Compared to ENE-, patients who were ENE+ had significantly higher rates of all-cause mortality (studies = 8; RR = 3.25; 95%CI: 1.35-2.64, I(2) = 83%) and recurrence (studies = 17; RR = 2.64, 95%CI: 1.93-3.60, I(2) = 73%). Using HRs adjusted for potential confounders, ENE+ status carried a significantly higher risk of all-cause and cancer-specific mortality and disease recurrence.


CONCLUSIONS
It becomes mandatory to consider ENE in the histopathological examination of surgical samples in thyroid cancer patients, and this factor should be included in future oncological staging systems.
Geriatrics Division, Department of Medicine, University of Padova, Padova, Italy.
Nicola
N
Veronese
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Claudio
C
Luchini
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Alessia
A
Nottegar
Department of Molecular Pathology, Tohoku University School of Medicine, Sendai, Japan.
Takuma
T
Kaneko
Geriatrics Division, Department of Medicine, University of Padova, Padova, Italy.
Giuseppe
G
Sergi
Geriatrics Division, Department of Medicine, University of Padova, Padova, Italy.
Enzo
E
Manzato
Department of Neurosciences, University of Padova, Padova, Italy.
Marco
M
Solmi
Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
Aldo
A
Scarpa
D006801:Humans; D008207:Lymphatic Metastasis; D011379:Prognosis; D013964:Thyroid Neoplasms / Q000401:mortality* / Q000473:pathology*
extranodal extension; prognosis; survival; thyroid cancer