Prognostic impact of N staging in 715 medullary thyroid cancer patients: proposal for a revised staging system

This institutional study aimed at quantifying a medullary thyroid cancer (MTC) patient's risk of lung, liver, or bone metastasis.

Without quantitative information regarding risk factors for lung, liver, and bone metastasis, risk stratification is liable to be haphazard, resulting in poor cost-effectiveness of screening programs.

Included in this study were 715 patients with MTC for whom histopathologic information was available for each lymph node removed.

Seventy-two patients (10.1%) were diagnosed with lung metastasis, 58 patients (8.1%) with liver metastasis, and 34 patients (4.8%) with bone metastasis. Multivariate analyses were limited to patients revealing no more than 1 type of distant metastasis to avoid confounding by other distant metastasis. Extrathyroidal extension and 1 to 10 involved nodes indicated a small risk of lung metastasis [3%-4%; odds ratio (OR) 3-4], tumors greater than 40 mm and 11 to 20 involved nodes implied an intermediate risk (13%; OR 6), and more than 20 involved nodes entailed a high risk (26%-30%; OR 14-16). In the multivariate logistic regressions on liver and bone metastasis, in which the number of involved nodes was omitted on statistic grounds, extrathyroidal extension signified a strong risk of liver metastasis (19%, OR 23), whereas no clinical-pathologic variables were significantly associated with bone metastasis. Cumulative rates of lung, liver, and bone metastasis, plotted against the number of lymph node metastases, were similar.

N categories encompassing 1 to 10 (N1), 11 to 20 (N2), and more than 20 (N3) lymph node metastases are important prognostic classifiers that should be incorporated into MTC staging systems for better risk stratification.