Sarcopenia vs body mass index (BMI) as a prognostic biomarker in patients with metastatic clear cell renal cell carcinoma (mCCRCC) in the era of first line immune checkpoint inhibitors (ICIs).
Authors: La Course Bryce Douglas , Orcutt Delaney , Gross Evan , Fintelmann Florian J. , Master Viraj A. , Hall Evan Thomas , Wrobel Maria Marta , Psutka Sarah P. 
Published: June 2023

e16515

Background: ICIs are an important systemic treatment option for patients with mCCRCC. Sarcopenia, defined as low muscle mass, is associated with inferior outcomes in mCCRCC. However, there is limited data regarding sarcopenia and overall survival (OS) in patients receiving treatment with ICI-based regimens. Our objective was to evaluate associations between sarcopenia and BMI with OS in patients with mCCRCC receiving first line ICIs. Methods: A retrospective review of patients with mCCRCC receiving first line ICI-based therapy at Fred Hutchinson Cancer Center between 1/2015 to 4/2022 was performed. Patients without CT scans within 75 days of treatment initiation were excluded. Skeletal muscle index (SMI) at the level of L3 was measured using validated techniques. Sarcopenia was classified according to an international definition (SMI < 55 cm2/m2 for men and SMI < 39 cm2/m2 for women). BMI was defined as underweight ( < 19 kg/m2), normal (19-24.99kg/m2), overweight (25-29.99 kg/m2), and obese ( > 30 kg/m2). OS was estimated using the Kaplan-Meier method. Associations with OS were evaluated with Cox proportional hazard model analysis. Results: A total of 96 patients (25% female) with a median age of 62 (Interquartile range, IQR 55-68), met inclusion criteria. Due to missing CT images, 9 (9%) patients were excluded. 10 (11%), 43 (49%), and 22 (25%) were International Metastatic RCC Database Consortium (IMDC) favorable, intermediate, and poor risk respectively (12 unknown). Median follow up was 23 months (IQR 12-35). First-line therapy included ICI monotherapy (N = 15), ipilimumab/nivolumab (N = 49) or ICI/VEGF targeted therapy (N = 23). In total, 43 (49%) patients were sarcopenic. Median OS overall was 42.6 months (IQR 15.9-NR). Two-year OS was 57% in sarcopenic vs 76% in non-sarcopenic patients (Log-Rank p = 0.06). On multivariable analysis adjusted for IMDC risk criteria, age, and gender, SMI (continuous) was independently associated with survival (HR 0.94, 95%CI 0.90-0.99, p = 0.03) while BMI was not significantly associated with OS on univariate or multivariable analyses (p > 0.05). Among the 49 patients receiving ipilimumab/nivolumab combination therapy, sarcopenia was significantly associated with decreased 2-year OS (47% vs. 77%, p = 0.02). Across IMDC risk strata, sarcopenia was significantly associated with decreased 2-year OS in the intermediate risk group only (44% vs. 83%, p = 0.01). Conclusions: Sarcopenia, but not BMI, is independently associated with OS among patients with mCCRCC receiving first line ICI-based regimens. This finding is consistent with the literature suggesting that muscle mass measurement provides an important prognostic biomarker for patients with mCCRCC. SMI could inform treatment selection and adoption of muscle measures when risk-stratifying this population should be considered.