Body composition, ClearCode34, and survival in localized clear cell renal cell cancer

BACKGROUND: Poor muscle health is an adverse prognostic factor in clear cell renal cell cancer (ccRCC), but mechanisms are unknown. We examined associations among six body composition features, ClearCode34 tumor molecular subtype, and survival. METHODS: In a cohort of 837 patients with localized ccRCC, we segmented pre-surgical CT scans for cross-sectional areas and radiodensities of skeletal muscle, visceral adiposity, and subcutaneous adiposity. RNA was extracted from archived tumor specimens and run on a custom Nanostring array. A centroid- based classification categorized tumors as ccA (less aggressive) or ccB (more aggressive) ClearCode34 subtype. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body composition and ClearCode34 subtype. Hazard ratios (HRs) and 95% CIs were estimated for individual and joint effects of body composition features and ClearCode34 subtype on 5-year disease-free survival (DFS). RESULTS: The cohort was predominantly male, white, and had Stage I disease; 26% of tumors were ccB subtype. 95 DFS events occurred over 3532.2 person-years of follow-up. Patients with lower skeletal muscle radiodensity (SMD) were more likely to harbor ccB tumors (OR per 10-unit decrease in SMD: 1.30, 95% CI: 1.00-1.69). Exploratory joint effects analyses suggested patients with lower SMD and ccB subtype experienced the lowest DFS compared to patients without those characteristics (HR 2.68, 95% CI: 1.43-5.00). CONCLUSIONS: ccRCC patients with lower SMD (more fat- infiltrated skeletal muscle) at diagnosis may experience worse survival because they harbor more aggressive tumors. Future studies should determine how post-nephrectomy changes in body composition features are associated with survival.