4. Discussion
The development of VEGF pathway blocking agents led to a significant breakthrough in the outcome of mRCC patients. Besides, immune checkpoint inhibitors are used either alone or in combination with VEGF blocking agents for the treatment mRCC patients [20, 21]. With the availability of alternative treatment options, novel prognostic markers are of paramount importance to provide better personalized treatments. Current prognostic scoring systems have been developed based on clinical and laboratory parameter values [3, 4]. Obesity is not included among these values, and its impact on the prognosis of mRCC patients is still controversial [22]. For this reason, in addition to BMI; VBC measurements, suggested as more reliable indicators of obesity, have been investigated in our study. In the present study, the impact of baseline VBC and sarcopenia parameters as well as their post-treatment changes at the third-fourth month in the mRCC patients treated with targeted therapy were analyzed. To the best of our knowledge, we for the first time analyzed the associations of several VBC parameters and their changes with PFS and OS in one cohort. Although obesity is a well-defined risk factor for RCC; as a paradox to this situation, we found that TATI, SATI, and VATI were independent predictive factors for OS.
Body composition may be defined as the amount and distribution of lean tissue, fat tissue, and bones. Up to this decade, studies on body composition and clinical outcomes of mRCC have been mainly investigated with BMI values. However, the exact amount of fat tissue or rate of fat to muscle tissues could not be predicted from BMI values alone. With advances in imaging technologies, specific analysis of muscle and fat tissue may be obtained from CT taken for the staging of oncologic diseases, and response assessment purposes. Thus, in addition to BMI, the studies focused on the measurement of SAT and VAT components of the intra-abdominal fat tissue at the umbilicus-level using CT. Steffens et al. conducted a study focusing on the impact of VAT and SAT on the prognosis of 116 mRCC patients and found that contrary to the BMI, above average values for VFA and SFA are related to longer PFS and OS in mRCC patients (SAT; HR: 3.41, 95% CI: 1.61–7.25, P=0.001; VAT; HR: 2.97, 95% CI: 1.36–6.47, P=0.006) [8]. Ladoire et al. assessed the prognostic value of SAT, VAT, and BMI in 64 mRCC patients treated with targeted therapy using same measurement techniques as in the Steffens’ trial [17]. However, they reported that high VAT was associated with significantly worse OS (HR: 6.26, 95% CI: 2.29–17.08, P<0.001) [17]. The contradicting results in these studies may have been due to cut-off points not defined per gender and/or CT measurements of VBC through umbilicus level. It would be incorrect to evaluate the CT measurements taken at this level to estimate the full-body fat and muscle tissues. Hence, VAT and SAT were not associated with prognosis of mRCC in a study by Antoun et al. when these measurements were performed on a more appropriate level as L3 and adjusted per gender [19]. Additionally, these studies were performed with baseline measurements. Based on these results, VBC were measured with at the L3 level and adjusted according to gender in the present study and we also evaluated the effect of CT measurement changes (the value between the initial CT and the CT performed 3-4 months after treatment initiation) on PFS and OS.
Nevertheless, the present study had several limitations. Firstly, the study population was relatively small and consisted of single-center patients. Secondly, the present study had a retrospective design and the relatively short median follow-up time. Furthermore, because most patients in our cohort were categorized as an intermediate-risk group (61%), our results should be further investigated in favorable and poor risk groups in a more homogeneous population. From this perspective, these disparate results in the literature mentioned above may emerge from an disparity in prognostic factors not regulated in one study than in another.