Association between Immune Checkpoint Inhibitor Treatment Outcomes and Body Composition Factors in Metastatic Renal Cell Carcinoma Patients

Simple Summary Although body composition-related biomarkers are associated with the prognosis of patients with cancer, whether they are associated with the therapeutic effects of immune checkpoint inhibitors remains unclear. We found that among body composition-related biomarkers, sarcopenia based on skeletal muscle mass was strongly associated with the treatment efficacy of immune checkpoint inhibitors in patients with metastatic renal cell carcinoma. However, body composition-related biomarkers based on subcutaneous or visceral fat were not associated with treatment efficacy. The skeletal muscle releases myokines to activate the immune system. Therapeutic interventions for sarcopenia may not only improve patients' quality of life but also improve the therapeutic effects of immune checkpoint inhibitors and prolong the prognosis of patients.Abstract Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of metastatic renal cell carcinoma (mRCC); however, validating body composition-related biomarkers for their efficacy remains incomplete. We evaluated the association between body composition-related markers and the prognosis of patients with mRCC who received ICI-based first-line therapies. Patients and Methods: We retrospectively investigated 60 patients with mRCC who underwent ICI-based therapy as their first-line treatment between 2019 and 2023. Body composition variables, including skeletal muscle, subcutaneous fat, and visceral fat indices, were calculated using baseline computed tomography scans. Sarcopenia was defined according to sex-specific cut-off values of the skeletal mass index. The associations between body composition indices and objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were evaluated. Results: Patients with sarcopenia had lower ORR and DCR than those without sarcopenia (33.3% vs. 61.1%, p = 0.0436 and 52.4% vs. 94.4%, p = 0.0024, respectively). Patients with sarcopenia had a significantly shorter median PFS (14 months vs. not reached, p = 0.0020) and OS (21 months vs. not reached, p = 0.0023) than patients without sarcopenia did. Sarcopenia was a significant predictor of PFS (hazard ratio [HR], 4.31; 95% confidence interval [CI], 1.65-14.8; p = 0.0018) and OS (HR, 5.44; 95% CI, 1.83-23.4; p = 0.0013) along with poor IMDC risk. No association was found between the subcutaneous, visceral, and total fat indices and the therapeutic effect of ICI-based therapy. Conclusions: Sarcopenia was associated with a lower response and shorter survival rates in patients with mRCC who received first-line ICI-based therapy.