The Role of Obesity in Renal Cell Carcinoma Patients: Clinical-Pathological Implications

Abstract

Obesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC–obesity link has not been fully addressed when considering a comprehensive scenario starting from pathogenetic aspects through pathological issues up to the outcome of medical treatment. We therefore conducted an electronic PubMed search using keywords “obesity”, “body mass index”, “overweight”, “renal cell carcinoma/kidney cancer”, “medical treatment”, “targeted therapy”, and “immunotherapy/immune checkpoint inhibitors”. The selected data supported a crosstalk between adipose tissue (adipocytes and other white adipose tissue cells) and cancer cells inducing several signaling pathways that finally stimulated angiogenesis, survival, and cellular proliferation. Accurate sampling of renal sinus fat correlated with a prognostic value. Retrospective clinical evidence in metastatic RCC patients with higher body mass index (BMI) and treated with targeted therapies and/or immune checkpoint inhibitors showed advantageous survival outcomes. Therefore, obesity may influence the course of RCC patients, although the interplay between obesity/BMI and RCC warrants a large prospective confirmation. We are therefore still far from determining a clear role of obesity as a prognostic/predictive factor in metastatic RCC patients undergoing targeted therapy and immunotherapy.

Immunohistochemical Expression of Chemokine Receptor CXCR4 as a Valuable Prognostic Marker in Renal Cell Carcinoma

“…RCC is the 6 th leading cause of cancerrelated mortality and it is the most lethal and aggressive urological cancer. The 5-year survival rate is about 65% [1]. CXCR4 is a G-protein coupled receptor that was initially described to mediate inflammatory response.…”

“…Peak incidence is in the 6 th decade of life with male to female ratio about 2:1. Incidence of bilaterality about 1% [1]. Nearly about 30 % of patients with RCC come with metastatic disease when diagnosed for first time and about 60% of those patients die from aggressive disease and metastasis.…”

Epidemiology, Predisposing Factors, Biomarkers, and Prevention Mechanism of Obesity: A Systematic Review

“…As indicated from another systematic review, obesity may influence the course of renal cell carcinoma (RCC) patients, although the interplay between obesity and RCC warrants a large prospective confirmation [68].…”

Biological Support to Obesity Paradox in Renal Cell Carcinoma: A Review

“…TNF-α can induce the release of other type 1 cytokines and angiogenic factors through cyclooxygenase 2 and prostaglandin E2 production, in turn favoring cancer de-Urol Int 2020;104:837-848 DOI: 10.1159/000510245 velopment and progression [27,28]. Further, through the NF-κB pathway, TNF-α can increase antiapoptotic factors such as BCL-2 and survivin in cancer cells, ensuring their survival and proliferation through the increase of cyclin D1 and cyclin E [15]. Other type 1 cytokines induced by TNF-α can exert antiapoptotic effects on cancer cells, while promoting their proliferation, through the PI3K/AKT pathway.…”