Prognostic Significance Of The Distribution Of Lymph Node Metastasis In Locally Advanced Rectal Cancer After Neoadjuvant Chemoradiotherapy

Objective: To explore the prognostic significance of the distribution of lymph node metastasis in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.Methods: We retrospectively collected clinical data of 725 patients with locally advanced rectal cancer who undergoing neoadjuvant chemoradiotherapy followed by radical surgery from December 2010 to December 2016 in our department,and 179 patients with positive lymph nodes were enrolled.The distribution of lymph node metastasis(LND)was evaluated with reference to the seventh edition of the Japanese Colorectal Cancer Protocol.Univariate analysis were used to analyze the clinicopathologic factors associated with LND by Kruskal-Wallis test and chi-square test or Fisher’s exact.The survival was estimated by the Kaplan-Meier method,and the differences between groups were compared with the Log-rank test.Multivariate analysis was performed by Cox proportional hazard model.Results:(1)A total of 179 patients,LND1,lymph node metastasis at the mesorectum(140/179,78.2%);LND2,lymph node metastasis along the trunk of inferior mesenteric artery(26/179,14.5%);LND3,lymph node metastasis at root of inferior mesenteric artery(13/179,7.3%).Clinicopathological factors are compared among three groups.Univariate analysis showed that preoperative CEA(P=0.022),complication(P=0.005),yp TNM stage(P=0.000),perineural invasion(P=0.005),and Lymphovascular invasion(P=0.036)and circumferential resection margin involvement(P = 0.021)were significantly associated with LND.(2)Univariate analysis showed LND showed superior discrimination for 3-year DFS(LND1 66.8%,LND2 50%,LND3 15.4%,P=0.000),3-year LRFS(LND1 77.6%,LND2 60.6%,LND3 23.1%,P=0.000)and 3-year DMFS(LND1 68.2%,LND2 49.7%,LND3 15.4%,P=0.000).yp N stage was not related to prognosis(3-year DFS,P =0.342;3-year LRFS,P = 0.061;3-year DMFS,P = 0.260).And there was no significant prognostic difference between the three groups in yp TNM stage(3-year DFS,P = 0.191;3 years LRFS,P = 0.198;3 years DMFS,P = 0.056).On multivariate survival analysis,LND was an independent prognostic factor for DFS,LRFS,and DMFS in patients with positive lymph nodes(P =0.000).(3)Thirteen patients(13/179,7.3%)with abnormal distribution of lymph node metastasis,which means metastasis at the proximal lymph nodes but negative in mesorectum lymph nodes.The 3-year DFS in this group was 38.5%,lower than the mesorectum lymph node(+)proximal lymph node(-)with no significant difference(3-year DFS,38.5% vs.66.8%,P = 0.079).There was no significant difference with the mesorectum lymph node(+)proximal lymph node(+)group(3-year DFS,38.5%vs.34.2%,P = 0.304).Conclusion: Patients with proximal lymph node metastasis show worse prognosis.LND is an independent prognostic factor for stage III patients with rectal cancer after neoadjuvant chemoradiotherapy,and it may play a complementary role to the existing yp TNM staging system.