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 16~124). 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. TRIAL REGISTRATION: Not applicable (retrospective study).