1. Introduction
Renal cell carcinoma (RCC) constituting 4 % of all cancers is the sixth
and the tenth most frequently diagnosed cancer type in men and women
worldwide, respectively [1]. Although most of the lesions detected
incidentally via developed imaging techniques were small and low-grade
tumors, 17% of all RCC cases present with distant metastasis at
diagnosis [2]. Due to recent advances, the first-line treatment for
metastatic renal cell carcinoma (mRCC) has evolved from cytokine-based
treatment to vascular endothelial growth factor (VEGF) pathway
inhibitors, immune checkpoint blockers, and their combination. To define
the prognosis of mRCC patients, two models named “International
Metastatic Renal Cell Carcinoma Database Consortium (IMDC)” and “The
Memorial Sloan-Kettering Cancer Center (MSKCC) Criteria” were
established, and mRCC patients were classified in terms of risk levels
as favorable, intermediate and poor [3, 4].
Although obesity is linked to increased risk of developing RCC,
underlying mechanisms of this link is poorly understood [5]. It has
been demonstrated that the biological mechanisms of obesity leads to
development of RCC including chronic tissue hypoxia, change of the
hormonal environment in the fat tissue, and immune dysfunction [6,
7]. Interestingly, some studies showed that obese mRCC patients have a
better response to treatment and thereby a better prognosis as it has
been named as the ‘obesity paradox’ in the literature [8, 9]. This
‘risk factor’ paradox may be due to the time gap between two detrimental
risk factors that overnutrition is a well known long-term killer but can
be a protective factor in the short term, while malnutrition is a
short-term killer [10]. Additionally, the decline of skeletal
muscle, called sarcopenia, has been reported as a predictor of prognosis
in various tumors including RCC [11-13]. Also, it has been shown
that the decline in skeletal muscle mass is related to increased side
effects in cancer treatment and worsened survival outcomes [14, 15].
Body Mass Index (BMI) is a rough sketch of the distribution of fat in
the body. Hence, BMI alone is not sufficient to detect the exact body
composition parameters and the sarcopenia, which is characterized by the
loss of body fat composition and skeletal muscle tissue. Computerized
tomography (CT) is routinely used to determine staging and treatment
response evaluation of RCC. This technique allows for the better
categorization of fat and skeletal muscle tissue. Additionally, CT can
be used in the relative classification of the fat tissue in visceral and
subcutaneous compartments [visceral adipose tissue (VAT) and
superficial adipose tissue (SAT)]. The studies on the effects of these
parameters on the prognosis of mRCC delivered different results.
Steffens et al. [8] and Gu et al. [16] demonstrated that the
higher VAT and SAT were correlated with prolonged OS in mRCC patients.
Contrary to these findings, increased VAT was found to be correlated
with poor outcomes in the Ladoire’s cohort [17]. A study by Antoun
et al. demoonstrated no correlation between VAT or SAT and survival
outcomes in patients with mRCC [18]. It has been shown that body
weight and tissue loss can contribute to predicting the prognosis of
mRCC patients treated with targeted therapy [19]. However, few
studies have evaluated the prognostic value of longitudinal changes in
parameters of body composition over time in mRCC patients treated with
targeted therapy. The current study aimed to investigate whether or not
obesity and volumetric body composition (VBC) parameters can predict the
outcomes in mRCC patients treated with targeted therapy (pazopanib or
sunitinib) in terms of VAT, subcutaneous SAT, BMI, skeletal muscle area
(SMA) measurements and their changes after 3-4 months after initial CT.