Preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 for gastric cancer with extensive lymph node metastasis: 3-year follow-up results of JCOG1704.

396 Background: The prognosis for marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains unfavorable, even after R0 resection. Previous studies, which evaluated the efficacy and safety of preoperative chemotherapy with cisplatin plus S-1 (JCOG0405) and docetaxel with cisplatin plus S-1 (JCOG1002), reported that 3-year overall survival (OS) was 59% and 63%, respectively. Here, we report 3-year follow-up results of the phase II study (JCOG1704) of preoperative chemotherapy with docetaxel, oxaliplatin, and S-1 (DOS) which reported a major pathological response rate of 57%, including pathological complete response of 24% (Kurokawa Y, et al. Gastric Cancer 2024). Methods: Eligibility criteria included histologically proven HER2-negative gastric adenocarcinoma with bulky lymph node (BN) and/or para-aortic node (PAN) metastasis. Patients received three cycles of DOS (docetaxel 40 mg/m 2 , day 1, oxaliplatin 100 mg/m 2 , day 1, and S-1 80–120 mg/body, days 1–14) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. Results: Between October 2018 and March 2022, 47 patients (BN only 20, PAN only 17, both 10) were enrolled. Among the 45 patients excluding one ineligible patient and another who declined any protocol treatment before initiation, 44 (98%) completed three cycles of DOS, 42 (93%) underwent R0 resection, and 30 (67%) completed all protocol treatments including adjuvant chemotherapy with S-1 for 1 year. At the data cut-off of May 2025, 3-year OS and progression-free survival (PFS) in the 46 patients excluding one ineligible patient were 86.7% (95% confidence interval CI, 72.7–93.7%) and 75.6% (95% CI, 60.2–85.6%), respectively. In subgroup analysis according to node status, 3-year OS and PFS were 85.0% and 75.0% in 20 patients with only BN metastasis, 93.8% and 81.3% in 17 patients with only PAN metastasis, and 77.8% and 66.7% in 9 patients with both BN and PAN metastasis, respectively. Conclusions: Preoperative chemotherapy with DOS for gastric cancer with ELM showed favorable survival results compared to previous reports. Clinical trial information: jRCTs031180028 .