## 3 Discussion
### Body Composition  
[PERSON] et al. [38] investigated the body composition of 79 mRCC patients treated with ICIs for the evaluation of clinical outcomes through retrospective analysis [38]. Skeletal muscle, subcutaneous, intermuscular, and visceral adipose tissue densities were measured and converted to indices by dividing by height (m)\({}^{2}\); the total adipose tissue index was obtained from the sum of these indices. Most patients (59.5%) received ICI monotherapy, while the remaining patients were treated with the ICI combination regimen. Furthermore, most of the patients had intermediate (54%) and poor (30%) IMDC risk criteria. Multivariate Cox analysis found that patients with a low total fat index had a significantly lower overall survival (HR: 2.72, CI: 1.43-5.17, \(p\) = 0.002), a significantly lower progression-free survival (HR: 1.91, CI: 1.09-3.35, \(p\) = 0.025), and a lower chance of clinical benefit (OR: 0.25, CI: 0.09-0.70, \(p\) = 0.008). Kaplan-Meier analysis showed that patients with a higher total fat index had significantly higher overall survival and progression-free survival than patients with a low total fat index (44.5 vs. 14.1 months, \(p\) = 0.0012 and 8.4 vs. 2.9 months, \(p\) = 0.0015, respectively). Furthermore, the total fat index, compared to IMDC and body mass index, presented higher C-statistics for predicting overall survival, progression-free survival, and clinical benefit [38]. [PERSON] et al. [39] investigated the association between sarcopenia and nivolumab response in 96 mRCC patients [39]. Sarcopenia was assessed by measuring the skeletal muscle index (SMI) and psoas muscle index (cm\({}^{2}\)/m\({}^{2}\)) = ([skeletal muscle cross-sectional area at the level of L3]/[height]\({}^{2}\)). Most patients were treated with TKIs as prior therapy. Furthermore, most patients were categorized according to intermediate and poor IMDC risk criteria (54.2% and 41.7%, respectively). In relation to the skeletal muscle index, 71 patients presented sarcopenia (74%), while 24 patients were not sarcopenia (26%); meanwhile, considering the psoas muscle index, 33 patients presented sarcopenia (34.4%), and 63 patients were not sarcopenia (65.6%). Despite large discrepancies in the assessment of sarcopenia, a correlation was found between the two indices (r = 0.488; 95% confidence interval (CI), 0.319-0.627; \(p\) < 0.001). Patients with psoas-muscle-index-based sarcopeniahad shorter median overall survival (10.1 months vs. 48.4 months, \(p<0.001\)) and shorter progression-free survival (1.9 months vs. 8.3 months, \(p<0.001\)). In addition, multivariate analysis identified psoas-muscle-index-based sarcopenia as a significant and independent predictor of overall survival (hazard ratio (HR), 3.85; 95% CI, 2.04-7.26; \(p<0.001\)) and poor IMDC risk status (HR, 1.90; 95% CI, 1.03-3.50; \(p=0.041\)). Skeletal-muscle-index-based sarcopenia was not associated with overall survival in this study [39]. Since a high body mass index can lead to better outcomes of ICIs in mccRCC patients, [PERSON] et al. [40] evaluated the body composition in this category of patients [40]. Body mass index and various body composition parameters (i.e., SMI and multiple adiposity indices) acquired from pretreatment CT scans of 205 mccRCC patients were evaluated. Response to therapy was assessed using RECIST v1.1. Whole-transcriptome patterns with body composition patterns were also evaluated on a separate cohort of 62 primary tumor samples. Patients with a high body mass index had higher overall survival than normal-weight patients (unadjusted HR, 0.66; 95% confidence interval (CI), 0.45-0.97; \(p=0.035\)). Of the body composition variables, only SMI was associated with overall survival (unadjusted HR comparing low vs. high SMI, 1.65 (95% CI: 1.13-2.43); \(p=0.009\)); this association, however, became insignificant after adjusting for IMDC score and line of therapy. Increased angiogenic, inflammatory, and myeloid signals were detected in tumors of low-SMI patients [40].