The paradox of obesity as it relates to renal cell carcinoma (RCC), in that obesity has been associated with both increased risk for RCC and better prognosis from RCC, was reviewed in an article published in Endocrine-Related Cancer.
The obesity paradox was first described in 1999 after it was found that hemodynamic and metabolic disorders were more likely to occur among patients who were obese, but their clinical outcomes tended to be more favorable than their nonobese counterparts.
A possible mechanism for this paradox is that obese patients tend to be diagnosed earlier than nonobese persons, and therefore receive more prompt interventions.
For RCC, obesity confers a 1.5- to 2.5-fold relative increased risk. The mechanism for this increased risk is not fully understood; however, contributing factors are the proactive substances produced by fat cells, which regulate signaling pathways, and increased leptin levels, which stimulate cell proliferation.
At the same time, obesity has been linked with a 41% to 53% lower chance of RCC mortality and improved survival after treatment with tyrosine kinase inhibitors sunitinib, sorafenib, or pazopanib. However, there have been conflicting results published on the basis of defining obesity using BMI or visceral/subcutaneous fat areas.
Improved survival related to obesity may be due to the fact that patients who are obese develop more indolent tumors, as they are more likely to be diagnosed with lower stage cancer, smaller tumors, and without symptoms of distant metastasis. Another possibility is that the perturbation to fatty acid metabolism observed with obesity could impact tumor survival, as fatty acids are essential for tumor growth.
The obesity paradox in RCC has been based on retrospective data, and some discrepant evidence has been reported. Prospective studies are needed to better define and understand the obesity paradox in RCC.
Turco F, Tucci M, Di Stefano R F, et al. Renal cell carcinoma (RCC): fatter is better? A review on the role of obesity in RCC. Endocr Relat Cancer. Published online May 1, 2021. doi:10.1530/ERC-20-045