In this multicenter study conducted in northern China, our findings indicate that there were no statistically significant differences in the 3-year DFS between patients with AGC who underwent LDG or ODG with D2 lymphadenectomy. In multivariate analysis, a BMI of less than 25 kg/m2, pT4 stage, and pN2-3 status were identified as independent risk factors for patients with AGC following surgery.

Recently, the CLASS group was the first to report that LDG was not inferior to ODG in terms of 5-year OS in treating patients with AGC in China [11]. To our knowledge, this was also the first multicenter RCT to report 5-year survival outcomes for AGC patients globally. However, it is important to acknowledge the significant heterogeneity among gastric cancer patients from North and South China. Patients in the northern region of China are generally more obese than those in the South, due to geographical, dietary, and climatic factors [12]. Based on data obtained from a tertiary hospital in South Korea, it was found that male gastric cancer patients with a higher BMI exhibited significantly better prognoses compared to their female counterparts [13]. Furthermore, Matsui et al. conducted a study indicating that increased visceral fat mass could result in more post-gastrectomy complications; however, it might enhance OS rates for patients with AGC [14]. Notably, there is limited exploration into the disparities in DFS among AGC patients in North and South China.

In the KLASS-01 trials, the oncological outcomes of LDG for early gastric cancer (EGC) were previously presented [15]. The study demonstrates that the 5-year OS rates of LDG and ODG for EGC are similar at 94.2% and 93.3%, respectively, confirming the non-inferiority of LDG for EGC [15]. The advancements in surgical techniques have led to a progressive expansion of laparoscopy’s indications to AGC in eastern countries. Numerous high-quality RCTs have confirmed the safety and feasibility of laparoscopy for treating AGC [3,4,5]. A recent meta-analysis of five RCTs also demonstrated the equivalence between laparoscopy and open surgery regarding overall short-term morbidity and mortality for AGC [16]. However, unlike laparoscopy for EGC, the oncological prognosis of laparoscopy for AGC remains a concerning and controversial issue. This is primarily due to the complexity of laparoscopic lymph node dissection technology and the biological characteristics of AGC itself. Standardized lymph node dissection plays a crucial role in the oncological prognosis of gastric cancer, particularly in patients with AGC. Although the laparoscopic approach offers enhanced exposure, the role of LDG for AGC remains contentious due to the intricacies of D2 lymphadenectomy during in surgery. However, this study found that neither open nor laparoscopic surgical approaches were identified as risk or protective factors for DFS in cox regression analyses, consistent with the results of the CLASS-01 and KLASS-02 trials.

Disease-free survival (DFS) stands as the predominant endpoint in cancer clinical trials globally. In parallel to the CLASS-01 trials, where a margin of noninferiority of 10% was assumed, the ongoing multicenter investigation in northern China reveals that the 3-year DFS rates for AGC within the LDG group (85.98%) closely mirrors that observed in the ODG group (84.72%). These findings align with recent retrospective and prospective studies examining the oncological outcomes associated with laparoscopic versus open surgery for gastrectomy [17,18,19]. Meanwhile, using − 8% as the noninferiority margin, the noninferiority of LDG for AGC was also demonstrated by the recent KLASS-02 trials from Korea [9]. Despite the different noninferiority margins used by the clinical trial, their findings implied that LDG with D2 lymph node dissection is an optional treatment strategy for AGC. Furthermore, the subgroup analysis of our trials demonstrated that the rates of 3-year DFS rates on the ODG group and LDG groups for patients with different pathological stages were: stage I- 97.26% and 98.44% respectively; for patients with pathological stage II- 93.85% and 88.71%, respectively; for patients with pathological stage III 69.51% and 74.32%, respectively; and for patients with pathological stage IV 60% and 40%, respectively. In comparison to CLASS-01, this study observed a higher proportion of patients with early stage gastric cancer (31.8% vs. 29.2%) and a lower percentage of patients who underwent adjuvant therapy (39.4% vs. 47.7%). The observed disparity may account for the elevated 3-year DFS rate in this investigation compared to the CLASS-01 cohort, notwithstanding the congruence in inclusion and exclusion criteria between the two studies.

This study diverges from the conclusions drawn in the CLASS-01 and KLASS-02 trials by suggesting that a higher preoperative BMI correlates with improved DFS following distal gastrectomy in patients with AGC. While obesity is commonly identified as a cardiovascular risk factor, its impact on cancer remains equivocal [20].

Numerous studies have investigated the correlation between BMI and the prognosis of patients diagnosed with GC. Specifically, gastric cancer patients with elevated BMIs exhibited more favorable oncological outcomes post-gastrectomy compared to those with normal weight, particularly in Japan and Korea [13, 19]. Elevated BMI was observed to correlate with increased postoperative morbidity [21], however, its role as an independent prognostic factor for patients with AGC in China remains uncertain. Furthermore, previous studies have indicated that a higher BMI does not independently predict long-term survival among patients with GC in Western populations [22]. In our investigation, we have illustrated the adverse oncological prognosis observed in patients with a lower BMI subsequent to AGC diagnosis in northern China. Several potential mechanisms may underlie these findings, including the propensity for tumors to exhibit greater aggressiveness in underweight individuals compared to their obese counterparts. Several studies have demonstrated that individuals with higher BMI exhibit reduced cellular differentiation and decreased occurrence of lymph node metastasis [23, 24]. Also, patients with lower BMI usually have lower muscle mass, which might result in hampered immunity [25]. A meta-analysis conducted by Zhao B et al., which included 12 studies, revealed that underweight preoperative patients with GC were associated with a higher risk of death from causes other than cancer, especially infection [26]. Third, weight loss was often accompanied by gastrectomy or chemotherapy, which could affect DFS. A study reported that ideal body weight can be achieved by overweight patients following curative gastrectomy, which could lead to better long-term prognoses [23]. Therefore, the relationship between BMI and prognosis deserves further attention.

Several limitations of this study warrant consideration. Firstly, the limited participation of hospitals from other provinces in North China may have compromised the generalizability of the findings. Secondly, approximately 10% of patients initially diagnosed with advanced cancer stages were subsequently confirmed postoperatively to have stage I cancer, potentially impacting the reliability of the conclusions. Thirdly, this study lacked measurement of visceral adiposity or muscle mass for assessing obesity, representing a significant limitation. Finally, although there was no significant differences in 3-year DFS rate between the two groups and the outcomes of two groups seem to be comparable at a glance, these results never mean to prove the non-inferiority of LDG to ODG in this study design.