Purpose: Current staging systems for head and neck squamous cell carcinoma (HNSCC) incorporate lymph node (LN) size and laterality, but place less weight on the total number of positive metastatic nodes. We investigate the independent impact of numerical metastatic LN burden on survival.
Methods: Adult HNSCC patients undergoing upfront surgical resection for curative intent were identified in the National Cancer Data Base between 2004-2013. Oral cavity, larynx, and hypopharynx sites were included, with a neck dissection of minimum 10 LN required. Multivariable models were constructed to assess the association between number of metastatic LN and survival, adjusting for factors such as nodal size, laterality, margin status, and adjuvant treatment.
Results: Overall, 24,763 patients were identified (12,601 N0 patients, 12,162 N+ patients). For patients with 0, 1, 2, 3, 4-6, 7-9, and 10 or more metastatic lymph nodes, the 5-year OS was 65.7%, 50.3%, 42.8%, 36.4%, 30.2%, 18.7%, and 14.1%, respectively. A similar impact of number of metastatic lymph nodes was also seen in N2b and N2c subgroups. After adjustment for covariates, mortality risk increased continuously with increasing number of metastatic nodes without plateau, with the effect most pronounced up to 4 LN (HR 1.34, 95% CI 1.29-1.39, p<0.001). Lower neck involvement also predicted for increased mortality (HR 1.15, 95% CI 1.04-1.28, p=0.007). Increasing number of nodes examined was associated with improved survival up to 38 LN, albeit to a lesser degree than metastatic lymph node number (HR 0.99, 95% CI 0.98-0.99, p<0.001). In multivariable models accounting for number of metastatic nodes, contralateral LN involvement (N2c status) and LN size were not significantly associated with mortality.
Conclusion: Number of metastatic nodes is a critical predictor of HNSCC mortality, eclipsing LN size, laterality, lower neck involvement, and total nodes examined in prognostic value. More robust incorporation of numerical metastatic LN burden may augment staging and better inform adjuvant treatment decisions.