Para-aortic lymph node dissection following neoadjuvant chemotherapy for type 4 or large type 3 gastric cancer with extensive lymph node metastasis.

BACKGROUND: D2 and para-aortic lymph node dissection (PAND) following neoadjuvant chemotherapy (NAC) are reportedly effective for gastric cancer (GC) with extensive lymph node metastasis (ELM), such as para-aortic nodal metastasis or bulky nodal metastasis, around the major perigastric arteries. However, type 4 and large type 3 tumors were excluded from previous studies, as they are considered special subtypes that easily spread to the peritoneum. Whether or not PAND contributes to the survival of type 4 or large type 3GC with ELM is thus unclear. METHODS: This study examined patients who underwent radical gastrectomy with D2 resection and PAND following NAC between 2002 and 2019. Patients were classified into the normal-type group and the type 4 or large type 3 group. The overall survival (OS) and prognostic factors were investigated. RESULTS: Forty-nine patients were examined and classified into the normal-type group (34 patients) and type 4 or large type 3 group (15 patients). The 5-year OS rates of the normal-type and type 4 or large type 3 groups were 55.5% and 26.7%, respectively. Type 4 or large type 3 tumors were an independent risk factor for a poor prognosis in the multivariate analysis (hazard ratio: 2.506, 95% confidence interval: 1.111-5.650, and p = 0.027). CONCLUSIONS: The prognosis of type 4 or large type 3 GC with ELM treated with radical gastrectomy with D2 and PAND after NAC was poor. Type 4 or large type 3 GC with ELM should be treated using a different strategy than the normal type with ELM.

A Phase II study of preoperative chemotherapy with docetaxel, oxaliplatin and S-1 in gastric cancer with extensive lymph node metastasis (JCOG1704).

Background: Although surgical resection is necessary to cure the locally advanced gastric cancer, it is sometimes difficult for extensive nodal metastasis such as para-aortic nodal disease or bulky nodal metastasis around the major gastric branched arteries. We had conducted several Phase II studies and clarified preoperative chemotherapy with doublet regimen followed by surgery markedly improved the survival for this disease. Recently, preoperative chemotherapy with docetaxel, oxaliplatin and S-1 (DOS) showed promising efficacy and acceptable feasibility for resectable advanced gastric cancer. Aim: To describe the design and rationale for the multi-institutional, single-arm, Phase II trial of systemic chemotherapy with DOS followed by surgery in advanced gastric cancer with extensive lymph node metastasis (JCOG1704). If efficacy and safety of DOS can be shown, we will conduct a Phase III trial comparing preoperative DOS and current standard cisplatin and S-1. Trial registration: jRCTs031180028.

Long-term outcomes of preoperative docetaxel with cisplatin plus S-1 therapy for gastric cancer with extensive nodal metastasis (JCOG1002).

BACKGROUND: Preoperative chemotherapy with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis. In the JCOG1002, we added docetaxel to CS (DCS) to further improve long-term outcomes. However, the primary endpoint, clinical response rate (RR), did not reach the expected level (Ito et al. in Gastric Cancer 20:322-31, 2017). Herein, we report our long-term survival results. METHODS: Patients with BN and/or PAN metastasis received 2 or 3 cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1 and S-1 at 80 mg/m2 per day for 2 weeks, followed by a 2-week rest) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. RESULTS: Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% had both PAN and BN metastasis, and the rest had either PAN (26.4%) or BN (56.6%) metastasis. Among all eligible patients, the 5-year overall survival was 54.9% (95% confidence interval 40.3-67.3%) at the last follow-up in May 2018. Among 44 eligible patients with R0 resection, the 5-year relapse-free survival was 47.7% (95% confidence interval 32.5-61.5%). CONCLUSIONS: Adding docetaxel to CS in preoperative chemotherapy for extensive nodal metastasis improved neither short-term outcomes nor long-term survival. Preoperative chemotherapy with CS followed by D2 + PAN dissection and postoperative S-1 remains the standard of care for patients with extensive nodal metastasis.