An accurate cancer staging classification should ideally be widely accepted among surgeons, oncologists, and other physicians. [15] Moreover, it should also provide the clinician with information for the planning of treatment and evaluating the treatment results between different institutions and areas. [16]
From the 7th edition of the UICC/AJCC TNM staging system for esophageal carcinoma that had been used in 2010, the pN stage was classified according to the absolute number of involved LNs, rather than the simple classification of absent (pN0) or present (pN1) in the previous editions. Although the new pN stage was found to provide more accurate prediction of survival than the previous versions, this number-based pN stage still had some deficiencies. [4, 12, 17–21] The most important point was that stage migration usually occurred in this pN stage in patients with a small number of LNs examined. [22]
The number of LNs examined could vary significantly among different patient cohorts due to the different extents of lymphadenectomy. Thus, new prognostic nodal parameters were required to compensate for the deficiencies in these number-based pN stages. Previous studies have found that the LNR and LODDS might be superior to the pN stage because they were not significantly affected by the total number of LNs examined,[3–11] and some studies even found that LODDS might have better prediction of prognosis than the LNR. [6–8] However, controversy still exists,[23] and neither the LNR nor the LODDS stage has accurately and widely accepted criteria. Moreover, few studies have evaluated these two LN staging systems in ESCC. [12, 17–19]
In the current study, we used a large patient cohort with ESCC to compare the prognostic value of three LN staging systems (pN, LNR and LODDS). In order to minimize the impact of the pT stage on survival, we enrolled patients with a single pT3 stage for analyses, which consisted of the largest proportion of patients with ESCC in our study (38.8%, 1667/4298). All three LN staging systems were found to be significantly correlated with survival in univariate and multivariate analyses, and the corresponding AUC also showed that none of them differed significantly in predicting survival, indicating that they could be used for prognostic assessment in ESCC.
However, when we analyzed the survival of patients in each pN and LNR classification stratified by the LODDS, significant differences in survival were always found, with the exception of pN3, Nr2, and Nr3. However, survival was highly homologous when the LODDS classification was stratified by the pN or Nr category. Moreover, as the definition of the Nr0 category was the same as the pN0 category, both the pN and LNR staging systems could not discriminate the survival differences among patients with no LN metastasis. Due to its unique statistical characteristics, LODDS was the only LN staging system that could discriminate survival differences in patients without LN metastasis. All of these results suggested that LODDS might be superior to the other two LN staging systems.
The findings in our study that the LNR and LODDS staging systems could more accurately predict survival than the pN stage in patients with inadequate lymphadenectomy were consistent with previous studies. [3–11] In our study, we found that in most of the pN categories, better prognosis would always be found in patients with more extensive lymphadenectomy. However, survival was more homologous when subdividing the LNR and LODDS staging systems based on the extent of lymphadenectomy, except for the category of Nr0, which had the same definition as the pN0 category. These results did not mean that the LNR and LODDS staging systems were not influenced by the examined LN number. Theoretically, more extensive lymphadenectomies would always lead to the potential for better staging, not only for pN staging but also for LNR and LODDS staging. The corresponding AUCs for the LNR and LODDS staging systems in patients with adequate lymphadenectomy were higher than those in patients with inadequate lymphadenectomy, indicating that the accuracy of the LNR and LODDS staging systems was also positively correlated with the number of LNs examined. The superiority of prognosis assessment for the LNR and LODDS staging systems was that the influence of the number of LNs examined on them was smaller than that of the pN staging system. [23]
Our study has some limitations. First, this was a retrospective study from a single center. The retrospective nature may undermine the power of our study. Second, the patients enrolled in our study were from a long period with different surgeons and pathologists. As no widely accepted criteria have been established for LNR and LODDS staging for ESCC, whether our results can be applied to other studies still needs to be confirmed. We think that further multicenter, prospective studies are required to identify widely accepted criteria for LNR and LODDS staging in ESCC.
In conclusion, all three staging systems could be used for prognostic assessment in ESCC. However, the LNR and LODDS staging systems could more accurately predict survival than the pN staging system in patients with inadequate lymphadenectomy, and LODDS might be superior to the other two LN staging systems due to its unique statistical characteristics. Further studies are required to examine our findings and identify widely accepted criteria for LNR and LODDS staging in ESCC.