This study evaluated the prognostic value of the maximal lymph nodal diameter for NPC. The results revealed that NPC patients with the maximal lymph nodal diameter > 5.0 cm had worse OS and CSS compared to patients with the maximal lymph nodal diameter ≤ 5.0 cm. The results indicated that the maximal nodal diameter > 5.0 cm might be a reasonable cut-off value for N3 stage.
It is reasonable that the maximal lymph nodal diameter > 3.0–6.0 cm is not classified as N2 in the 8th AJCC edition according to the current study. The multivariate regression analysis of our study revealed that the maximal lymph nodal diameter > 3.0–6.0 cm was not an independent prognostic factor for OS, although it was an independent prognostic factor for CSS. Moreover, the results of training set and validated set both indicated that OS and CSS among patients with the maximal lymph nodal diameter ≤ 5.0 cm were not significant different. Our study suggested that the maximal lymph nodal diameter = 3.0 cm was not a reasonable cut-off value. Patients with the maximal lymph nodal diameter ≤ 5.0 cm should be treated as a whole group. Similarly, previous studies revealed that cut-off value set at 3.0 cm failed to show any independent prognostic value in survivals(1, 6, 7, 11).
The maximal lymph nodal diameter > 6.0 cm is still classified as N3 in the 8th AJCC edition. However, it might not be a reasonable cut-off value. The reasonable cut-off value still needs further investigation. Pan et al.(1) reported that differences in OS and distant metastasis-free survival were significant between all N categories setting the cut-off value = 6.0 cm. In contrast, several studies reported that the maximal lymph nodal diameter > 6.0 cm was not an independent prognostic factor(6, 7, 11–13). Moreover, the proportion of the maximal lymph nodal diameter > 6.0 cm is small, which was less than 4.5%(1, 6, 7, 11). Our study revealed the proportion of the maximal lymph nodal diameter > 6.0 cm was 5.50%, while the proportion of the maximal lymph nodal diameter > 5.0 cm was 10.3%. In future, the incidence of patients with the maximal lymph nodal diameter > 6.0 cm will greatly decrease due to improvements in diagnosis. Thus, our study proposed the cut-off value = 5.0 cm might be more reasonable.
Assessment of the maximal lymph nodal diameter in crucial. The maximal lymph nodal diameter was assessed by palpation in the last decade(14). However, palpation-determined nodal size differs among clinicians. The maximal lymph nodal diameter measured on images was more accurate than palpation-based greatest dimension. Because palpation might involve subcutaneous tissue and aggregated nodes(6). According to the 2008 Chinese edition staging system, the maximal lymph nodal diameter was measured in axial plot. It was reported that no measurements of longitudinal maximal lymph nodal diameter were made in the coronal or sagittal planes may lead to negative results(6). In contrast, Guo et al.(7) found that the maximal lymph nodal diameter measured in all the longitudinal, sagittal, and coronal planes was not a useful indicator in predicting the spread potential of NPC patients. It was suggested that the maximal lymph nodal diameter might not represent the tumor burden, which could be replaced by the tumor volume(15, 16) and metabolic tumor volume(17–20).
Distant metastasis is the main failure pattern of NPC(2, 3). Due to the limitations of SEER database, data of distant failure were not available. Thus, this study could not assess the association between the maximal lymph nodal diameter and distant-metastasis free survival. It was unknown whether the unfavorable OS and CSS of patients with maximal lymph nodal diameter > 5.0 cm were due to distant failure or not. Further studies should be conducted to assess the correlation.
In conclusion, this study proposed that the maximal lymph nodal diameter > 5.0 cm was a cut-off value for nodal staging. However, the prognostic significance of size criteria (> 5.0 cm vs ≤ 5.0 cm) still needs further evaluation in prospective multi-center cohort studies.