Prognostische Bedeutung der Nodal Ratio und der Number of Positive Nodes bei Patienten mit Plattenepithelkarzinomen des Kopf-Hals-Bereichs

The squamous cell carcinoma forming mainly lymphatic metastases is the most common histological entity in tumors of the upper aerodigestive tract. The presence of lymph node metastases correlates with a significantly reduced survival prognosis. The lymph node status therefore has a high predictive val-ue in patients with squamous cell carcinomas of the head and neck, so that accurate detection and elimination of the lymph node metastases is of elemen-tary importance. A growing number of studies, e.g. in patients with breast, rec-tum and bladder cancer, suggests that the ratio of the histologically positive lymph nodes (Number of Positive Nodes) to the total number of resected lymph nodes, the so-called Nodal Ratio, is of prognostic relevance. The aim of this study was to examine the extent to which the two parameters Nodal Ratio and Number of Positive Nodes are suitable for estimating the prognosis of pa-tients with squamous cell carcinoma of the head and neck and whether they provide additional information to the conventional TNM classification. A retrospective analysis of 221 patients with head and neck squamous cell carcinoma and clinical N+ neck who had received neck dissection between 1998 and 2009 as part of primary surgical therapy or after definite ra-dio(chemo)therapy (R(CH)T) was performed. The survival analysis, including the five-year survival rates, was carried out using the Kaplan-Meier method. Afterwards the possible influence of age, gender, primary therapy, postopera-tive treatment, TNM stage according to UICC 2010, Nodal Ratio and Number of Positive Nodes on survival was tested using univariate and multivariate analysis (Cox model). A p-value <0.05 was considered statistically significant. Patients with oropharyngeal carcinomas formed the largest group of patients with 39.4 % (n=87), followed by patients with hypopharyngeal carcinomas with 31.7 % (n=70). The mean age of the patients at diagnosis was 58.2 years. 59.3 % (n=131) of the patients underwent primary surgery, 40.7 % (n=90) re-ceived primary R(CH)T. Postoperatively, 42.1 % (n=93) of the patients re-ceived adjuvant R(CH)T, while 57.9 % (n=128) of the patients received no fur-ther therapy after the surgical removal of the tumor and the neck dissection. On average, 30.1 lymph nodes were removed during the neck dissection and 4.96 lymph node metastases (Number of Positive Nodes) were detected. The mean Nodal Ratio was 9.4 %, the median Nodal Ratio was 5.3 %. Kaplan-Meier analysis showed that five-year survival rates decrease as the Nodal Ratio increases. In univariate analysis Nodal Ratio ≥6-<12,5 % and ≥12,5 %, Number of positive Nodes pN=1, pN=2-<5 and pN≥5, the N stages N2b, N2c and N3 as well as the M stages M1 and Mx were significantly asso-ciated with reduced overall survival. Multivariate analysis confirmed the corre-lation with a poor survival prognosis for the parameters Nodal Ratio ≥6-<12,5 % and ≥12,5 %, Number of Positive Nodes pN=1, N stage N3 and M stage Mx. In uni- and multivariate analysis, postoperative treatment with R(CH)T was as-sociated with a prolonged overall survival and thus with a more favorable prognosis. Gender, age, T stage and type of primary therapy did not correlate significantly with survival in uni- and multivariate analysis. In summary Kaplan-Meier analysis as well as Cox-Regression showed that the Nodal Ratio is suitable as a prognostic parameter and that based on the Nodal Ratio patients can be divided into different risk categories. The Nodal Ratio is a solid prognostic parameter regarding overall survival, which can be determined independently of age, gender, tumor size and type of primary ther-apy (definite R(CH)T versus primary surgery). The Number of Positive Nodes also has prognostic relevance but is inferior to the Nodal Ratio in terms of its informative value. TNM classification did not provide consistent results in uni- and multivariate analysis. In multivariate analysis, only the N stage N3 and the M stage Mx showed to be of prognostic relevance. Overall TNM classification includes a great amount of indispensable information about the tumor and me-tastases but could benefit from the implementation of Nodal Ratio. The differ-ent, in some cases still very heterogeneous, cutpoints proposed for Nodal Ra-tio do not yet allow for a clear recommendation. Optimal cutpoints that assess the prognosis and benefit of intensified, adjuvant R(CH)T must be determined in large prospective studies.