Gastric cancer is a prevalent malignancy, accounting for 6.8% of cancer-related mortality worldwide (1). It is the fifth most commonly diagnosed cancer globally and ranks third in cancer-associated deaths (2). Gastric cancer is characterized by its asymptomatic onset, rapid progression, high degree of malignancy, and poor prognosis (3–5). The majority of patients are diagnosed at an advanced stage, significantly limiting the benefits of surgical intervention; many may even lose the opportunity for curative resection (6, 7). This highlights the necessity for more sophisticated and comprehensive therapeutic strategies aimed at disease control, symptom palliation, and improving overall survival and quality of life. While multimodal treatments such as combination chemotherapy (8) and immunotherapy (9) have demonstrated some efficacy in extending survival and enhancing quality of life, their overall clinical impact remains suboptimal.

Notably, with economic development, advancements in healthcare infrastructure, increased public health awareness, and the widespread use of antibiotics, the incidence of gastric cancer has declined compared to historical trends (1). However, an alarming rise in incidence is being observed in younger individuals, particularly those with obesity (10). Multiple studies have identified obesity as a significant risk factor not only for cardiovascular diseases but also for various malignancies, negatively influencing oncological outcomes (11, 12). Specifically, visceral obesity may facilitate tumorigenesis through the induction of adipose tissue inflammation and systemic inflammatory responses, leading to dysregulation of key signaling pathways in the adipose microenvironment and the tumor microenvironment (TME) (13, 14). Body mass index (BMI), defined as the ratio of body weight (kg) to the square of height (m²), is a widely utilized metric for evaluating excess adiposity and its severity (15, 16). While BMI is advantageous due to its simplicity, cost-effectiveness, and reproducibility, it fails to consistently reflect body fat distribution across individuals. Significant variability exists in body fat percentage at the same BMI across different age groups, genders, and ethnicities (17–19). In contrast, VFA is a more precise indicator of adipose tissue dysfunction and has been strongly linked to a range of obesity-related comorbidities (20, 21). Additionally, VFA has been proposed as a superior metric to BMI in assessing perioperative risk (22). Several studies have reported that increased VFA is associated with higher rates of postoperative complications in gastric cancer surgery, such as pancreatic fistula, anastomotic leakage (23), and surgical site infections (24). Moreover, elevated VFA has been correlated with worse clinical outcomes in patients with breast cancer, pancreatic cancer, and hepatocellular carcinoma (25–27).

Despite these findings, the prognostic significance of VFA in gastric cancer patients undergoing surgical or non-surgical treatment remains a matter of debate. Thus, elucidating the impact of visceral fat area on the prognosis of gastric cancer patients is of paramount importance. Quantitative measurement of body composition, including muscle and fat distribution, through computed tomography (CT) has been established as a reliable method for evaluating body composition (28–31), and has become a burgeoning area of research in oncology. Clinically, patients typically undergo axial abdominal CT scans in the supine position, with measurements commonly taken at the levels of L3, L4, and the umbilicus. Image analysis software is then employed to delineate visceral and subcutaneous fat compartments. The density of adipose tissue on CT images generally ranges between -150 and -50 Hounsfield units (HU), allowing for accurate identification and quantification of fat areas (measured in cm²).

This study employs a systematic review and meta-analysis to evaluate the association between VFA and the prognosis of gastric cancer patients, providing clinicians with a novel prognostic tool for use in clinical decision-making.

Gastric cancer (GC) is a leading cause of cancer-related mortality worldwide. Despite significant advances in treatment over recent years, the recurrence and mortality rates for gastric cancer remain high (45, 46). Complications following surgical treatment, along with adverse events from chemotherapy, immunotherapy, and targeted therapy, severely impact patient survival outcomes. Multiple studies have indicated that excessive abdominal visceral fat not only affects metabolic function but is also closely associated with postoperative complications and adverse events in gastric cancer patients (38–41). Additionally, adipose tissue secretes various factors, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6) (47, 48). These factors are not only associated with the mechanical effects of obesity, such as gastroesophageal reflux, but are also considered to play a significant pathological role in the development and progression of gastrointestinal cancers.Therefore, accurate prognostic assessment is crucial before performing radical gastric surgery or initiating non-surgical treatments such as combination chemotherapy.

BMI (Body Mass Index) is a commonly used indicator for assessing obesity, but it has significant limitations, particularly regarding accuracy across different ethnic groups. For instance, Asians often face a higher risk of cardiovascular diseases or metabolic syndrome at lower BMI levels (49). This discrepancy is largely due to differences in body fat distribution and percentage. BMI reflects only the ratio of weight to height, failing to distinguish between muscle and fat composition, and it does not effectively differentiate between peripheral obesity (fat accumulation in the limbs) and abdominal obesity (visceral fat accumulation), the latter of which is associated with greater health risks. Consequently, relying solely on BMI to assess health can overlook potential metabolic risks and variations in body composition. In contrast, visceral fat is a more reliable indicator of disease risk, with CT assessment considered the gold standard for detecting visceral fat obesity. Since Asians tend to accumulate visceral fat more readily, using visceral fat area (VFA) as an obesity assessment standard is more accurate than BMI and better reflects health risks.

Previous studies have shown that patients with higher intra-abdominal fat, such as those with pancreatic or colorectal cancer, tend to have poorer overall survival rates. This may be due to visceral fat increasing serum levels of inflammatory cytokines, angiogenic factors, and oxidative stress markers, thereby affecting the tumor microenvironment (50–52). However, in contrast to these findings, Harada et al. (53) demonstrated that low visceral fat could significantly increase overall mortality in patients with upper gastrointestinal cancers. Many researchers believe that high BMI or high VFA correlates with poor prognosis in gastric cancer patients, as previous studies have shown a strong association between high BMI or VFA and decreased postoperative morbidity and lymph node retrieval (54–56). Feng et al. (57) found that preoperative low VFA and significant postoperative VFA loss predicted shorter progression-free survival and overall survival in metastatic gastric cancer patients. Similarly, Park et al. (58) reported that a marked reduction in postoperative VFA was indicative of shorter progression-free and overall survival. Furthermore, Matsui et al. (59) identified low VFA as an independent prognostic factor for poor adherence to adjuvant chemotherapy in advanced gastric cancer patients requiring neoadjuvant treatment. Likewise, Zhang et al. (36) noted that lower VFA before and after neoadjuvant chemotherapy correlated with worse progression-free and overall survival. In summary, the impact of high VFA on survival outcomes in gastric cancer patients post-surgery or after non-surgical treatment remains unclear.

The purpose of this study was to determine whether VFA can serve as a prognostic indicator for assessing the prognosis of gastric cancer patients after treatment. To clarify the impact of high VFA on survival outcomes in gastric cancer patients following surgery or non-surgical treatment, we conducted a comprehensive meta-analysis of data from 12 relevant trials involving 6,054 patients from three countries. Our analysis confirmed the favorable impact of higher visceral fat on the prognosis of gastric cancer patients. Patients with higher visceral fat had longer overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) compared to those with lower visceral fat. The pooled hazard ratio (HR) for OS was 0.76 (95% CI = 0.65–0.90, P = 0.001), and the pooled HR for DFS or RFS was 0.84 (95% CI = 0.75–0.95, P = 0.004). This suggests that the beneficial impact of visceral fat on the prognosis of gastric cancer patients outweighs its potential harmful effects. In addition, our subgroup analysis indicated that higher VFA was predictive of more favorable OS and DFS or RFS outcomes regardless of sample size (≥500 or <500), cut-off value (100 or ≠100), study design (retrospective or prospective), and analysis type (multivariate or univariate). Notably, heterogeneity in OS might be attributed to differences in studies with sample sizes of <500, cut-off values ≠100, or retrospective designs. Heterogeneity in DFS or RFS might be due to differences in sample sizes <500 or studies using multivariate analysis. To assess potential publication bias, we employed several methods, including funnel plot analysis, Begg’s test, and Egger’s test. Sensitivity analysis and assessment of publication bias further corroborated the robustness of the conclusions drawn in this meta-analysis. Some clinical trials found no significant correlation between VFA and prognosis in gastric cancer patients. We consider the following possible reasons for this inconsistency: First, insufficient sample sizes in some trials may have led to result bias (35). Second, differences in baseline characteristics among patients could lead to variations in treatment outcomes. For example, in Taniguchi’s study, a higher proportion of patients with low visceral fat content received neoadjuvant or adjuvant therapy, which improved the long-term prognosis of this group (40). Third, treatment protocols varied across different centers. When the negative impact of higher VFA outweighs its benefits, the correlation with favorable prognosis may be obscured. There are several limitations to our study. First, there was heterogeneity among the included studies. Patient baseline characteristics, VFA cut-off values, and treatment protocols varied across trials. Second, the sample size in this analysis was relatively limited, with most data derived from Asian countries. Therefore, the value of VFA in European and other populations requires further exploration to determine its applicability across different demographics. Third, despite differences in body composition and hormones between men and women, we were unable to conduct a gender-based analysis due to the limitations of the original literature. Consequently, more high-quality, large-sample, prospective studies are needed in the future to validate and refine our findings.

This meta-analysis demonstrated that among patients with gastric cancer who underwent surgery or other treatments, elevated VFA was significantly associated with improved OS and DFS. Consequently, VFA may serve as a useful prognostic indicator for assessing the prognosis of gastric cancer patients following treatment. However, further prospective studies are necessary to validate these findings and confirm the reliability of VFA as a prognostic marker.