A homogenized approach to classify advanced gastric cancer patients with limited and adequate number of pathologically examined lymph nodes

Background:The prognosis of gastric cancer patients with a limited number of pathologically examined lymph nodes(eLN,<16)is dismal compared to those with adequately eLN(≥16),yet they are still classified within the same subgroups using the American Joint Committee on Cancer(AJCC)staging system.We aimed at formulating an easy-to-adopt and clinically reliable stratification approach to homogenize the classification for these two categories of patients.Methods:Patients staged according to the 8th AJCC pathological nodal(N)and tumor-node-metastasis(TNM)clas-sification were stratified into a Limited and Adequate eLN cohort based on their number of pathologically examined LNs.The statistical differences between the 5-year overall survival(OS)rates of both cohorts were determined and based on which,patients from the Limited eLN cohort were re-classified to a proposed modified nodal(N′)and TNM(TN′M)classification,by matching their survival rates with those of the Adequate eLN cohort.The prognostic perfor-mance of the N′and TN′M classification was then compared to a formulated lymph-node-ratio-based nodal classifica-tion,in addition to the 8th AJCC N and TNM classification.Results:Significant heterogeneous differences in 5-year OS between patients from the Limited and Adequate eLN cohort of the same nodal subgroups were identified(all P<0.001).However,no significant differences in 5-year OS were observed between the subgroups N0,N1,N2,and N3a of the Limited eLN cohort when compared with N1,N2,N3a,and N3b from the Adequate eLN cohort,respectively(P=0.853,0.476,0.114,and 0.230,respectively).A novel approach was formulated in which only patients from the Limited eLN cohort were re-classified to one higher nodal subgroup,denoted as the N′classification.This re-classification demonstrated superior stratifying and prognostic ability as compared to the 8th AJCC N and lymph-node-ratio classification(Akaike information criterion values[AIC]:12,276 vs.12,358 vs.12,283,respectively).The TN′M classification also demonstrated superior prognostic ability as compared to the 8th AJCC TNM classification(AIC value:12,252 vs.12,312).Conclusion:The proposed lymph node classification approach provides a clinically practical and reliable technique to homogeneously classify cohorts of gastric cancer patients with limited and adequate number of pathologically examined lymph nodes.