Relative visceral fat may predict prognosis for women with kidney cancer

High relative visceral fat areas (rVFA) may increase the risk of death for female patients with renal cell carcinoma (RCC) and provide a new risk stratification system, according to a study published in Radiology.

Prior studies have shown that sex may play a role in the outcomes of various types of cancer, possibly due to metabolic differences between men and women. Body fat distribution is different between men and premenopausal women, and it may impact overall survival (OS).

High levels of visceral fat have been associated with poorer outcomes in some cancers, but the evidence in RCC is conflicting.

Gerard K. Nguyen, MD, and colleagues from the Washington University School of Medicine in St Louis, MO, retrospectively evaluated the outcomes of patients with clear cell RCC to determine the association of sex, body fat composition, and tumor glucose metabolism.

To differentiate and determine the amount of subcutaneous and visceral fat, CT scans were normalized against total fat area to obtain the rVFA and relative subcutaneous fat.

The impact rVFA on sex-specific survival was evaluated using baseline CT images of 222 patients (145 male, 77 female) obtained from The Cancer Imaging Archive (TCIA) Kidney Renal Clear Cell Carcinoma (KIRC) database.

To evaluate sex differences in metabolism, 39 glycolytic genes in tumors from these patients were obtained from The Cancer Genome Atlas. Key mutations in clear cell RCC were analyzed for association with rVFA and tumor glycolytic profiles.

The median OS was not significantly different between men and women; however, women with an rVFA > 30.9% had a median OS of 40.4 months. Women who had lower rVFA had a median OS that exceeded the observation period (P < 0.001).

No correlations were found between visceral fat and length of survival among men.

Women, but not men, exhibited a significant positive correlation between rVFA and age, suggesting that rVFA in women could increase as a function of age.

The investigators speculated that declining levels of circulating estrogen shift adipose tissue deposition away from subcutaneous fat and toward visceral fat in postmenopausal women. In addition, estrogen may play a role in tumor metabolism in RCC.

Women with a high rVFA had a statistically significant increased risk of death (P=0.028) when compared with women with low rVFA (hazard ratio [HR]: 3.66). No increased risk of death was observed for high vs low rVFA in men (HR: 1.13).

There were no significant differences in rVFA between high- and low-glycolysis groups in either men or women, suggesting that rVFA and tumor glycolysis may operate independently.

Women in the study could be synergistically stratified using rVFA and tumor glycolysis. A combination of low rVFA and low tumor glycolysis identified a cohort of 19 women with an exceptional prognosis and zero deaths (P < 0.001), whereas the prognosis for women with either high rVFA or high glycolysis was worse.

Although men with low rVFA and low glycolysis performed better than the rest of the groups (P=0.026), these differences were not as robust as in women.

The researchers admit that the study has some limitations. The nonrandomized retrospective design and small sample size may have led to selection bias. In addition, thresholds were defined and evaluated on the same patient population, gene expression of the glycolytic pathway was used as a surrogate marker for glucose metabolism, and most of the participants in this study were white (91.4%).

“We propose a new sex-based stratification system that integrates the sex of the patient, visceral fat quantity, and tumor metabolism,” the authors concluded.

In addition: “The unique ability of our imaging strategy to risk-stratify women with clear cell RCC using a combination of visceral fat and tumor metabolism suggests a synergy between host and tumor metabolism that directly plays a role in outcomes independent of conventional assessments of prognosis (eg, grade and stage).”

The investigators suggested that this could be important in determining the initial prognosis in patients with RCC. Moreover, it is possible that prognosis could be improved with dietary interventions and exercise to modulate metabolism.

To read more about this study, click here.