OBJECTIVETo investigate the rationality of N3 classification and its sub-classification in the 7th UICC/AJCC TNM classification system.

METHODSClinicopathological data of 610 patients with stage N3 advanced gastric cancer who underwent standard D2 and D2+ radical surgery at the Department of Surgical Oncology, The First Hospital of China Medical University, from January 1980 to March 2010 were analyzed retrospectively. Patients were divided into N3a and N3b groups, and clinicopathological characteristics and prognosis were compared between N3a and N3b patients. Overall survival rate was determined using the Kaplan-Meier estimator. The log-rank test was used to identify differences between the survival curves of different groups. In multivariate analysis, Cox proportional hazard model was used to identify independent factors associated with prognosis.

RESULTSAmong 610 patients, 426 were men and 184 were women, 394 were N3a and 216 were N3b, with a mean age of(57±11) years old (range 23 to 83). A total of 19 842 lymph nodes were examined, in which 9 575 nodes were positive, with the metastatic ratio of 48.3%. The 5-year overall survival rate was 20.0%. Univariate analysis of prognostic factors suggested that tumor location (P=0.000), tumor size (P=0.003), Borrmann type (P=0.000), pathologic type (P=0.043), lymphatic vessel invasion (P=0.000), growth pattern (P=0.019), invasion depth (P=0.000), resection extent (P=0.000) and N3 sub-classification (P=0.000) were significantly associated with the prognosis of N3 patients. Further analysis showed that tumor size (P=0.028), invasion depth (P=0.000) and gastric resection extent (P=0.002) were significantly associated with the prognosis of N3a patients, while Borrmann type (P=0.034), lymphatic vessel invasion (P=0.002), invasion depth (P=0.008) and resection extent (P=0.003) were significantly associated with the prognosis of N3b patients. Multivariate analysis revealed that lymphatic vessel invasion (P=0.009), resection extent (P=0.001), invasion depth (P=0.000) and N3 sub-classification (P=0.000) were independent prognostic factors of N3 patients; resection extent (P=0.004) and invasion depth (P=0.001) were independent prognostic factors of N3a patients; lymphatic vessel invasion (P=0.006) and invasion depth (P=0.009) were independent prognostic factors of N3b patients. Comparison of 5-year survival rate revealed that there was significant difference between T2-4N3a and T2-4N3b patients (P=0.000), while there was no significant difference between T2N3a and T2N3b patients (P=0.140). On the contrary, there were significant differences between T3N3a and T3N3b patients, T4aN3a and T4aN3b patients, T4bN3a and T4bN3b patients, respectively (all P<0.05). Further comparison demonstrated that there were significant differences between T4aN3a and T4bN3a patients, T4aN3b and T4bN3b patients, respectively (P=0.000, P=0.041). Besides, there were no significant differences in 5-year survival rate between T2N3 (at present, staged as III(A), T3N3a (III(B) and T4aN3a (III(C) patients(P=0.506), and T3N3b (III(B), T4aN3b (III(C) and T4bN3a (III(C) patients(P=0.283), respectively.

CONCLUSIONSN3 sub-classification should be included in the final TNM classification system. It is suggested that T2N3, T3N3a and T4aN3a may be categorized into III(A stage, T3N3b, T4aN3b and T4bN3a may be categorized into III(B stage,T4bN3b may be categorized into III(C stage or IIII( stage.