Abstract
Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor pathway and the mammalian target of rapamycin (mTOR) pathway. Obesity confers a higher risk of RCC. However, the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. This review focuses on the impact of body composition on targeted therapy outcomes in mRCC. The International Metastatic Renal Cell Carcinoma Database Consortium database has the largest series of patients evaluating the impact of body mass index (BMI) on outcomes in mRCC patients treated with targeted therapy. Overall survival was significantly improved in overweight patients (BMI ≥ 25 kg/m2), and this observation was externally validated in patients who participated in Pfizer trials. In contrast, sarcopenia is consistently associated with increased toxicity to inhibitors of angiogenesis and mTOR. Strengthening patients with mRCC and sarcopenia, through a structured exercise program and dietary intervention, may improve outcomes in mRCC treated with targeted therapies. At the same time, the paradox of obesity being a risk factor for RCC while offering a better overall survival in response to targeted therapy needs to be further evaluated.
Highlights
Treatment of metastatic renal cell cancer currently focuses on inhibition of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin pathway
Frequency of sorafenib-induced doselimiting toxicities was highest in sarcopenic patients whose body mass index (BMI) < 25 kg/m2, and lowest in nonsarcopenic patients who were overweight or obese (p = 0.03) [24]. These results suggest that sarcopenia in metastatic renal cell cancer (mRCC) is a predictor of sorafenib-induced toxicity
The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) database has the largest series of patients evaluating the impact of BMI on outcomes in mRCC patients treated with targeted therapy
Summary
Treatment of metastatic renal cell cancer (mRCC) currently focuses on inhibition of the vascular endothelial growth factor (VEGF) pathway and the mammalian target of rapamycin (mTOR) pathway. Two commonly used models include the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model [1] and the Memorial SloanKettering Cancer Center (MSKCC) criteria [2, 3] (Table 1). Obesity confers a higher risk of RCC [4,5,6,7]; the influence of obesity on clinical outcomes in mRCC in the era of targeted therapy is less clear. Higher BMI may negatively influence outcomes through commonly associated comorbidities of diabetes and cardiovascular disease [9]. It may alter drug concentrations and pharmacokinetics of targeted therapies that are dosed independent of weight. Body composition on targeted therapy outcomes in mRCC
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