Discussion
In this study, the prognostic implications of the volume of the lymph node, or the nodal volume, in oral tongue cancer were described for the first time. The 1-year survival rate in our study was 51%, which was slightly lower than the 1-year survival rate of oral cavity cancer stage III and IV reported by the National Cancer Intelligence Network (NCIN) (10). The difference could be partially explained by the different population and ethnicity.
From the ROC curve analysis, the optimal cut-off level of the nodal volume of 3.95 cm3 illustrated the diagnostic capability of the nodal volume to determine the survival outcomes, including overall survival and distant metastasis-free survival (sensitivity = 65.5%, and specificity = 73.3%). In multivariate analysis, only the nodal volume, but not the TNM stage, was a prognostic factor for distant metastasis-free survival (Adj HR = 4.45, p = 0.036, 95%CI = 1.1-17.94).
In general, the TNM staging system is used to predict the disease prognosis. The staging system mainly focuses on the size of the primary tumor and its invasion to the adjacent organs. Apart from the tumor size, the role of the tumor volume, or the overall volume of the primary tumor, predicting the disease prognosis has been reported with increasing evidence. Strongin A et al. indicated the tumor volume of >35 cm3, but not the TNM stage was associated with the poor prognosis for recurrence and distant metastasis. (4) Lin CS et al. also revealed that the tumor volume was associated with the recurrent rate and the death rate. (6)
In our study, the role of the nodal volume on its prognostic implications was explored and demonstrated the significant association between the nodal volume and the disease prognosis. The study emphasized the superiority of the nodal volume over the TNM stage on predicting the disease prognosis, particularly the distant metastasis-free survival.
In multivariate analysis, the larger nodal volume (optimal cut-off volume = 3.95 cm3) was significantly associated with the likelihood of distant metastasis. The association between the nodal volume and the overall survival was also likely, but not statistically significant. (Adj HR = 1.8, p=0.062, 95%CI = 0.97-3.34) The non-significance may be partly due to the small number of patients. With the smaller nodal volume, the N stage was likely to be lesser, andvice versa . Therefore, the patients in the groups classified by the nodal volume were not evenly distributed in terms of the N stage, thus affecting the statistical analysis.
In our study, the nodal volume revealed its prognostic implications over the TNM stage in terms of distant metastasis. This finding reflects the possible role of the nodal volume to improve the prognostic implications of the current TNM staging system, in which only the tumor size and the number of lymph node involvement are included.
Due to the retrospective design, some information was unavailable. A limitation of the study was the measurement technique of the nodal volume, in which only the CT or MRI scan imaging of the lymph node that contained the characteristics of possible metastasis were included. Therefore, the lymph node of size <1 cm, which may be metastatic, was excluded from the measure, which affected the total nodal volume. Due to the single-center study with limited number and distributions of the patients, further multi-center study with more number and distributions of the patients may provide more precise data and warrant the subgroup analysis, including comparing the nodal volume in the patients with the same N stage, to define the prognostic implications of the nodal volume and the N stage.