Efficacy of capecitabine and oxaliplatin versus S-1 as adjuvant chemotherapy in gastric cancer after D2 lymph node dissection according to lymph node ratio and N stage

Background: We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging. Methods: Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0-0.1, 0.1-0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups. Results: After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16 similar to 124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group. Conclusions: LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1.