Racial differences in kidney cancer histology and outcome: A nationwide study from the UroCCR Cohort.

Abstract

Racial differences in renal cell carcinoma (RCC) have been well described in U.S. cohorts, particularly for common histologic subtypes. However, such differences remain underexplored in European populations, especially for rare RCC subtypes and within universal health care settings. We aimed to characterize racial differences in RCC histology, renal comorbidities, and clinical outcomes in France, and to investigate potential molecular underpinnings. A total of 9404 patients were analyzed from the UroCCR national registry (1987-2024), including 338 Black and 9066 non-Black individuals with nephrectomy-confirmed diagnoses. Clinical features, histologic subtypes, and outcomes were compared between groups. Transcriptomic differences between Black and White individuals were assessed using publicly available single-nucleus and bulk RNA-sequencing data from nonneoplastic renal tissue. Clear-cell RCC was less common in Black patients (47.6% vs. 68.8%), whereas papillary, translocation, and fumarate hydratase-deficient RCC subtypes, as well as angiomyolipoma, were more prevalent (all odds ratios ≥ 2). Black patients were diagnosed younger, with smaller, earlier-stage tumors, and underwent partial nephrectomy more frequently. No difference in disease-specific survival was observed; however, distant recurrence-free survival was longer in Black patients (hazard ratio, 0.54; p = .019), likely reflecting earlier diagnosis. Race was not associated with survival after adjusting for clinical factors. Transcriptomic profiling revealed upregulation of adipogenic and angiogenic programs in White individuals and enrichment of hemoglobin- and chemokine-related pathways in Black individuals. Limitations include retrospective design and race classification. Distinct racial patterns in RCC histology and renal biology may inform subtype susceptibility. These findings support ancestry-informed strategies in RCC diagnosis and research.