Number of nodal metastases and prognosis in metastatic cutaneous squamous cell carcinoma of the head and neck

Background: Existing prognostic systems for metastatic cutaneous squamous cell carcinoma of the head and neck (cSCCHN) do not discriminate between the number of involved nodes beyond single versus multiple. This study aimed to determine if the number of metastatic lymph nodes is an independent prognostic factor in metastatic cSCCHN and whether it provides additional prognostic information to the American Joint Committee on Cancer (AJCC) staging. Methods: We retrospectively analysed 101 patients undergoing curative intent treatment for metastatic cSCCHN to parotid and/or neck nodes by surgery +/− radiotherapy at Liverpool Hospital, Sydney, Australia. The impact of number of nodal metastases on disease-free survival (DFS) and risk of distant metastases was assessed using multivariate Cox regression. Results: The mean number of nodal metastases was 2.5 (range 1–12). On multivariate analysis, increasing number of nodal metastases significantly predicted reduced DFS (hazard ratio 1.17; 95% confidence interval 1.05–1.30; P = 0.004), with a 17% increased risk of recurrence or death for each additional node. This remained significant in multivariate models adjusted for AJCC 8th edition nodal and TNM stages. Number of nodal metastases was also associated with risk of distant metastatic failure (hazard ratio 1.21; 95% confidence interval 1.05–1.39; P = 0.009). Conclusion: Increasing number of nodal metastases is associated with decreased DFS and increased risk of distant metastases in metastatic cSCCHN, with a cumulative risk increase with each additional node. It provides additional prognostic information to the AJCC staging, which may be improved by incorporating information on the number of nodal metastases beyond the current single versus multiple distinction.