Gastric cancer is one of the most common malignant tumors and leading causes of death worldwide. Gastric cancer tends to metastasize, and the incidence of proximal gastric cancer is gradually increasing. According to the Japanese Gastric Cancer Association, locally advanced upper one-third gastric cancer (AUTGC) is recommended for total gastrectomy plus D2 lymph node dissection. However, whether the splenic 门 lymph nodes (LN-10) should be included in the D2 dissection range, and whether LN-10 affects patient prognosis, remains controversial. Previous prospective studies achieved LN-10 dissection through spleen resection, which did not affect prognosis but increased postoperative complications. Laparoscopic technology for gastric cancer treatment is safe and feasible. Single-center studies have also shown that laparoscopic preserving spleen splenorenal lymph node dissection is feasible. However, there is a lack of high-quality clinical evidence. Therefore, a team from Union Hospital, Fujian Medical University, led a prospective multicenter study, CLASS-04, to explore the long-term efficacy of laparoscopic total gastrectomy plus preserving spleen splenorenal lymph node dissection (LSTG) for locally advanced proximal gastric cancer (AUTGC) and the impact of splenic 门 lymph nodes (LN-10) metastasis on patient prognosis. The results were published in the JAMA Network Open journal.

CLASS-04 was a prospective, multicenter, single-arm study conducted at 19 centers in China. It enrolled patients diagnosed with T2/T3/T4a upper one-third gastric cancer (AUTGC) without distant metastasis between September 1, 2016, and October 31, 2017. The last follow-up date was December 31, 2020. The primary study endpoints were 3-year overall survival (OS) and disease-free survival (DFS). Multivariate analysis was used to explore the correlation between LN-10 metastasis and survival.

A total of 246 patients (mean [SD] age 60.1 [9.4] years; 197 [80.1%] male) were included in the intention-to-treat analysis. Regarding clinical TNM staging, 14 patients (5.7%) were stage I, 104 patients (42.3%) were stage II, and 128 patients (52.0%) were stage III.

The mean (SD) number of resected LNs was 42.1 (16.2), and LN-10 metastasis occurred in 19 patients. The LN-10 metastasis rate (7.7%) was higher than that of LN-5 (3.7%), LN-6 (4.5%), LN-11d (6.5%), and LN-12a (1.6%). A total of 223 patients (90.7%) had tumors located in the non-greater curvature of the stomach, and 182 patients (74.0%) received adjuvant chemotherapy postoperatively. The rate of early complications was 14.2%, with local complications accounting for 8.5% and systemic complications for 6.9%.

With a median follow-up of 36.0 months (IQR, 35.0-37.3 months), 45 patients died. The 3-year OS rate for all patients was 79.1% (95% CI, 74.0%-84.2%), and the 3-year DFS rate was 73.1% (95% CI, 67.4%-78.8%). The 3-year OS rate for stage I patients was 97.4%, for stage II patients was 89.0%, and for stage III patients was 67.4%. The 3-year DFS rate for stage I patients was 97.4%, for stage II patients was 84.5%, and for stage III patients was 58.8%.

55 patients experienced recurrence. The most common was peritoneal recurrence (7.3%), while local recurrence occurred in 3.3%, distant metastasis in 4.1%, and multiple site metastasis in 5.7%. The treatment value index for LN-10 resection at 3 years was 4.5, higher than that of some D2 LN groups: LN-5 (2.1), LN-6 (2.5), LN-11d (4.1), and LN-12a (0.4) resection.

Patients with LN-10 metastasis had significantly lower 3-year OS and DFS rates compared to non-LN-10 metastasis patients (3-year OS, 63.2% vs 80.4%; P = 0.001; 3-year DFS, 47.4% vs 75.3%; P < 0.001).

However, factor analysis revealed that LN-10 metastasis was associated with poor prognosis (OS: HR = 3.06; 95% CI, 1.50-6.26; P = .002; DFS: HR = 2.70; 95% CI, 1.38-5.29; P = .004). Further multivariate analysis confirmed that LN-10 metastasis was an independent poor prognostic factor for OS (HR = 2.38; 95% CI, 1.08-5.25; P = 0.03) and DFS (HR = 2.28; 95% CI, 1.12-4.63; P = 0.01). Coexisting diseases (≥≡) were also independent prognostic factors for OS (HR, 2.58; 95% CI, 1.45-4.58; P < .001) and DFS (HR, 2.35; 95% CI, 1.39-3.96; P = 0.001), as well as TNM Stage III (OS: HR, 3.95; 95% CI, 1.91-8.18; P < 0.001; DFS: HR, 3.47; 95% CI, 1.83-6.56; P < 0.001) and adjuvant chemotherapy (OS: HR, 0.29; 95% CI, 0.16-0.53; P < .001; DFS: HR = 0.37; 95% CI, 0.21-0.64; P < 0.001).

Patients with LN-10 metastasis had a significantly higher 3-year recurrence rate post-surgery compared to non-LN-10 metastasis patients (42.1% vs 20.7%; P = 0.03), especially in multiple site metastasis patients (21.1% vs 4.4%; P = 0.01). However, in other recurrence patterns, the two groups were similar.

Among the 19 patients with LN-10 metastasis, 16 were clinical stage II and 3 were stage III. Of these, 14 patients (73.7%) received adjuvant chemotherapy, while 5 patients (26.3%) refused further treatment. The long-term survival of LN-10 metastasis patients who received adjuvant chemotherapy was significantly better than that of those who did not receive adjuvant chemotherapy (OS: HR=0.07; 95% CI, 0.01-0.37; P = .002; P =0.003). Similar to patients without LN-10 metastasis (OS: HR=1.05; 95% CI, 0.33-3.37; P =0.94; DFS: HR, 1.50; 95% CI, 0.60-3.74; P =0.39).

In summary, studies indicate that for patients with AUTGC, laparoscopic total gastrectomy with spleen-preserving splenic hilar lymphadenectomy (LSTG) yields long-term clinical efficacy. Patients with LN-10 metastasis have a poorer prognosis and are prone to recurrence.