Background: Creatinine and cystatin C are routinely used to assess renal function. Given creatinine originates from skeletal muscle and cystatin C is produced by nucleated cells, a creatinine to cystatin C ratio (Cr/Cys-C) may positively correlate with muscle mass. Low Cr/Cys-C has also been associated with decreased overall survival (OS) in cancer, including in a combined cohort of genitourinary malignancies. Furthermore, elevated cystatin c has been associated with shorter OS and recurrence free survival (RFS) in renal cell carcinoma (RCC). Cr/Cys-C may be a simple and affordable tool to assist with patient-specific risk stratification. We assess the ability of Cr/Cys-C to predict OS and RFS in patients with RCC. Methods: Retrospective review of a prospectively maintained database identified patients that underwent partial or radical nephrectomy for RCC from 2018-2021. Included patients had preoperative creatinine and cystatin C and 1+ year of follow up. Cr/Cys-C associations with patient/tumor characteristics were determined by generalized chi-square or Fisher’s exact tests for categorical variables and Wilcoxon rank-sum test for continuous variables. Cr/Cys-C ability to predict OS and RFS was analyzed with Kaplan-Meier method and Cox hazards models. Statistical tests were two-sided with type I error set at 0.05. Results: 219 patients were identified. Median age was 64, with most being male (67%). 62% and 29% of patients were white and black, respectively. Median eGFR was 72mL/min/1.73m2. Median (IQR) Cr/Cys-C was 1 (0.8-1.2). 55% were stage T3-T4, with 12% N1 and 16% M1 at time of surgery. 72% had clear cell histology. Low Cr/Cys-C was significantly associated with older age, males, Eastern Cooperative Oncology Group score ≥ 1, radical nephrectomy, T3-T4 stage, and metastasis. Kaplan-Meier curves showed low Cr/Cys-C association with decreased OS (p=0.0003) and RFS (p=0.0094). Cox regression analysis revealed lower Cr/Cys-C as independent predictor of decreased OS (binary HR=3.66, 95% CI 1.2-11.3, p=0.02; continuous HR=0.05, 95% 0.0-0.8, p=0.03) and RFS (binary HR=4.8, 95% CI 1.6-14.6, p=0.006; continuous HR=0.02, 95% 0.0-0.3, p=0.006;Table). Conclusions: Lower Cr/Cys-C may be associated with decreased OS and RFS in patients with RCC.

Nonsignificant in OS: Age, race, gender, ECOG ≥ 1, obesity, diabetes, M1, and clear cell histology. Nonsignificant in RFS: Age 65+, male sex, ECOG, obesity, diabetes, nephrectomy type, T stage, N-stage, clear cell histology, grade, and tumor width. Abbreviations: Creatinine to cystatin-c ratio (Cr/Cys-C); Eastern Cooperative Oncology Group (ECOG).