RCC: Fat linked with increased death risk

High levels of visceral fat were associated with a significantly increased risk of death in women with clear cell renal cell carcinoma (RCC), but not in men, results of a recent retrospective study show.

Conversely, the combination of low visceral fat and low glucose metabolism pinpointed a subset of women with clear cell RCC who had excellent prognosis, according results of the study, which were published online ahead of print in Radiology (March 20, 2018).

Those findings suggest visceral fat and tumor glucose metabolism might be combined in a risk stratification system that could be interpreted differently, based on the sex of the patient, said investigator Joseph E. Ippolito, MD, PhD, of Mallinckrodt Institute of Radiology, Washington University in St. Louis School of Medicine.

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“There has been some evidence here and there about the role of visceral fat in the kidney, but I think we're basically one of the first, if not the first, to show that there could actually be sex differences in how this plays out prognostically,” Dr. Ippolito said in an interview with Urology Times.

Previous studies have shown that increased visceral fat correlates with poor outcomes in patients with colorectal and pancreatic cancers, while results of RCC studies have been mixed, Dr. Ippolito said. Moreover, these analyses generally have not looked at sex-specific differences in outcomes.

To determine whether sex differences in visceral fat composition predicted survival in this cohort, the investigators measured visceral fat in computed tomography (CT) images from 222 patients with clear cell RCC. Images were obtained from The Cancer Imaging Archive, the public resource that provide clinical images matched to subjects in The Cancer Genome Atlas (TCGA) and other genomics archives.

To control for concomitantly high subcutaneous fat in obese patients, they specifically looked at relative visceral fat area (rVFA), or visceral fat as a percentage of total fat area.

Next: What the authors found

They found that women with an rVFA greater than 30.9% had a median overall survival of 40.4 months, while women under that threshold had a median overall survival exceeding the observation period (p<.001).

To their surprise, investigators were unable to find a similar rVFA threshold that would stratify men for overall survival.

Moreover, multivariate analysis controlling for age, stage, and tumor size showed that high rVFA increased risk of death versus low rVFA in women (HR, 3.66; 95% CI, 1.64-8.19), but not in men (HR, 1.13; 95% CI, 0.58-2.18).

Investigators also looked at TCGA to obtain data on tumor expression of 39 glycolytic genes for these patients. They found a subset of 13 genes that predicted worse overall survival in women.

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By combining the visceral fat and glucose metabolism data, they identified a subset of 19 women with “exceptional prognosis and zero deaths,” Dr. Ippolito and colleagues reported.

These findings raise the possibility that certain dietary approaches targeting metabolism could be used as “sex-specific treatment options,” investigators concluded.

“We're looking at how the tumor metabolizes nutrients, and tumors need nutrients to grow, but what about the patients themselves?” Dr. Ippolito said in the interview.

“A patient's body is basically a reservoir for nutrition for the tumor,” he continued. “So we can start thinking about cancer not only as isolated, sitting in a kidney, but also in the context of systemic metabolism."

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