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

Background Prognosis of marginally resectable gastric cancer with extensive lymph node metastasis (ELM) remains poor, even after R0 resection. JCOG0405 established preoperative cisplatin plus S-1 as a provisional standard of care in Japanese guidelines, based on a favorable 3-year overall survival (OS) of 58.8%. We report the 3-year survival outcomes of JCOG1704, a phase II trial evaluating preoperative docetaxel, oxaliplatin, and S-1 (DOS) for marginally resectable gastric cancer with ELM, following promising short-term outcomes. Methods Patients with histologically confirmed HER2-negative gastric adenocarcinoma and bulky nodal (BN) involvement and/or para-aortic node (PAN) metastasis were eligible. Patients received three cycles of DOS (docetaxel 40 mg/m 2 , day 1; oxaliplatin 100 mg/m 2 , day 1; S-1 80–120 mg/m 2 , days 1–14) every 3 weeks, followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. Results Between December 2018 and March 2022, 47 patients (BN only, 20; PAN only, 17; both, 10) were enrolled. At the data cutoff date (May 2025), the 3-year OS and progression-free survival (PFS) were 86.7% (95% CI 72.7–93.8%) and 75.6% (95% CI 60.2–85.6%), respectively, among 46 eligible patients. Among 42 patients who underwent R0 resection, the 3-year relapse-free survival (RFS) was 78.6% (95% CI 62.9–88.2%). In subgroup analyses, the 3-year OS/PFS/RFS were 85.0%/75.0%/77.8% in BN only, 93.8%/81.3%/86.7% in PAN only, and 77.8%/66.7%/66.7% in both. Conclusions Preoperative DOS for gastric cancer with ELM yielded unprecedentedly favorable 3-year survival outcomes and was considered a provisional standard of care without a phase III trial within our JCOG community.