The association between visceral adipose tissue (VAT) and cancer development has been a subject of controversy. Several studies have reported no significant impact of VAT on mortality or survival rates in patients with colorectal cancer (CRC) [11, 19, 20]. However, conflicting findings suggest that high VAT levels are associated with poorer prognosis. For instance, Moon et al. found that viscerally obese patients (with a visceral fat area-to-subcutaneous fat area ratio > 0.5) had shorter disease-free survival (HR 1.98, 95% CI 1.02–3.87, p = 0.044) in resectable colorectal cancer, although it did not significantly affect overall survival [21]. These contradictory results might be attributed to the patients' pre-existing obesity-related conditions and the prior administration of neoadjuvant chemoradiation and surgical resection. In contrast, Park et al. demonstrated that visceral obesity tended to result in significantly decreased lymph node metastasis and better overall survival for CRC [12]. Hence, the existing evidence does not entirely align. The discrepancies might arise from variations in the parameters and methodologies used to measure VAT, as well as the heterogeneous characteristics of the patient populations. Additionally, insufficient sample sizes and different cut-off values for VAT could also contribute to the varied interpretations of the results.
This study found that male patients with advanced colorectal cancer and high visceral fat area (VFA) had a more favorable prognosis, even after considering other recognized risk factors such as body mass index (BMI) and skeletal muscle index (SMI), using restricted cubic spline analysis. This suggests that a high VFA may indicate better physiological reserves, while a low VFA could suggest malnutrition or nutritional deficiencies [22]. Patients with low visceral fat content might experience pre-cachexia and have poor response to anticancer therapy [23, 24, 25].
Although obesity is commonly considered a risk factor for cancer development, some retrospective studies, especially in patients treated with immune checkpoint inhibitors, have shown that higher BMI is associated with improved prognosis, known as the 'obesity paradox' [26, 27]. The exact mechanism behind this paradox is still unknown but could be related to the impact of obesity on the immune system and tumor microenvironment due to factors like leptin and lecithin. Obese patients may have better tolerance to treatment [28]. In this study, male patients with advanced colorectal cancer and high VFA had lower platelet-to-lymphocyte ratio (PLR) and higher hemoglobin (HB) levels, indicating better response to anticancer treatment and suggesting better energy reserves to cope with negative energy balance [29, 30].
Furthermore, the study identified gender differences in the results. Higher VFA was associated with a better prognosis in men (p < 0.05), whereas no significant difference was observed in women. However, the restricted cubic spline analysis showed a trend toward better prognosis with higher VFA in women as well. These discrepancies may be attributed to sex differences in hormone levels and immunological variations. It is well-known that women tend to store more body fat in the gluteal-femoral region, while men have higher visceral fat accumulation [31]. Recent studies have revealed that male mice have more regulatory T cells (Treg) in their visceral fat compared to female mice. Male VFA Treg cells express specific markers and hormones that regulate inflammatory mediators within the visceral fat. The recruitment of Treg cells is influenced by sex hormones and certain chemokines. However, there is still limited knowledge regarding the immune differences between males and females, the impact of VFA, and its role in cancer, necessitating further exploration [32].
This study utilized bioelectrical impedance analysis (BIA) as a non-invasive, simple, reproducible, and cost-effective method to measure VFA. It provides reliable and portable body composition assessment in clinical practice compared to other methods like magnetic resonance imaging (MRI), computed tomography (CT), or blood sampling. Restricted cubic splines were employed to better describe the relationship between VFA and clinical outcomes compared to other non-linear regression models.
In conclusion, this study demonstrates that VFA can serve as an indicator to assess obesity and metabolic status, as well as predict disease prognosis in patients. This finding prompts further consideration regarding the optimal nutritional status for intermediate to advanced cancer patients. It raises questions about balancing the benefits of visceral fat reserves with the detrimental effects of metabolic syndrome and chronic inflammation associated with high visceral fat. Additionally, investigating the relationship between skeletal muscle mass, visceral fat, and cancer patients' outcomes remains crucial. However, there are some limitations to consider. The absence of metabolic diseases among the studied patients with advanced colorectal cancer might overlook the impact of VFA as a metabolic tissue on body metabolism and alter patient prognosis. Furthermore, only physical indicators (VFA, SMI, and BMI) were measured initially, without considering potential changes during disease progression or the impact of VFA changes on SMI, BMI, and disease prognosis. The study also did not delve into changes in sex hormones, which requires further investigation.
Overall, this study highlights that higher VFA is associated with a better prognosis in male patients with advanced colorectal cancer. This finding persists even after adjusting for skeletal muscle mass and weight, as demonstrated by the Kaplan-Meier survival curves.