An optimal cancer staging classification should be able to group cases of similar prognosis within the same stage but separate it from adjacent stages and this should be reproducible and validated by different databases of the same cancer diagnosis making it applicable worldwide.
The recently released eighth edition of the American Joint Committee on Cancer TNM staging system (AJCC-8 TNM) for gastric cancer attempts to define prognosis, and determine the best treatment approach. Classifying cancer using tumor, lymph node, metastasis (TNM) system many view that it can accurate predict clinical outcome both at initial presentation and after surgical treatment and help to improve cancer treatments. On the other hand, cancer biology and the discovery of molecular factors that try to foretell treatment outcome and response have led some experts to question the utility of a TNM-based approach [Citation1].
Compared to other malignancies, gastric cancer is relatively rare, but is one of the major causes of cancer-related mortality worldwide [Citation2]. TNM staging system for gastric cancer published for the first time in the 2nd edition of the TNM Classification of Malignant Tumors in 1974 [Citation3]. The International Gastric Cancer Association (IGCA) retrospectively collected a significant number of patients who underwent a curative resection from gastric cancer from institutes around the world, although the majority from Eastern countries [Citation4]. The updated TNM staging system has been suggested and adopted to better reflect the prognostic relevance of the different stages and it is the one to be used since the beginning of 2018.
In this 8th edition there are some notable modifications, including the segmentation of N3 category into N3a (7–15 positive regional lymph nodes) and N3b (>15 positive regional lymph nodes). Consequently, the T1N3bM0 of stage IIB was moved to IIIB, the T2N3bM0 of stage IIIA was moved to IIIB, the T3N3bM0 of stage IIIB was moved to IIIC, and the T4aN3aM0 of stage IIIC was moved to IIIB [Citation4,Citation5]. Further on, there was a T4 stage migration, specifically T4bN0M0 and T4aN2M0 of stage IIIB moved to IIIA, and T4bN2M0 of IIIC moved to IIIB.
The validation of the new system has not been always proven successful though [Citation6], raising the question if a better way of classification could be considered. In the current issue of the journal, a modification of the 8th edition of the AJCC for the pathological staging of gastric cancer is suggested based on the survival difference observed in more than 8000 gastric cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database [Citation7].
Authors identified that by regrouping certain stage III patients to a lower (T4aN0M0 to IIB from IIIA) or higher stage, can better separate the survival of these patients in the newly formed group. Indeed, there twas significantly increase in Hazard Ratios (HRs) in the modified staging system and the concordance index (C-index) was significantly different between the modified (mAJCC-8) and the 8th (AJCC-8) staging system. Nevertheless, the numerical difference is small while no difference can be observed in the C-indices in the whole cohort or even between the mAJCC-8 and AJCC-7 on stage III group.
Another, really useful information to be considered in the pathologic staging of gastric cancer is the number of LNs harvested during gastrectomy. The significance of resection sufficient number lymph nodes had been already reported previously in the literature [Citation8]. Particularly, 15 LNs are considered as the minimum number of LNs needed to be removed to characterize a good quality surgery but obviously more than 15 LNs are needed to be able to differentiate between N3a and N3b stages. Interestingly, Ye at al. recently validated that at least 30 LNs should be the optimal number of nodes harvested during the operation and this was suggested to be included in a modified AJCC-8 staging system [Citation9]. Someone could argue though that this finding would not be reproducible in the Western world since it is not routine to dissect as many lymph nodes.
In conclusion, different ways to classify gastric cancer and in particular stage III disease is an ongoing demand to better characterize this disease. It seems though that even if regrouping the patients between different substages there will be a plateau that the current TNM staging can achieve beyond which different ways of staging could be considered. The incorporation of molecular biomarkers or biology driven classifications into the staging systems could potentially better predict prognosis and treatment selection, driving forward the route for personalized or precision medicine. The results of this study seem to add a different perspective on how gastric cancer should be staged, but they should be validated in a different dataset and ideally in a prospective collection of data.
Author contributions
All authors equally contributed to this article with conception and design of the study, literature review and analysis, drafting and critical revision and editing, and final approval of the final version.
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References
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