Validation of novel grading schemes and refinement of the Leibovich risk groups for chromophobe renal cell carcinoma

Background: Traditional grading systems have proven inadequate in stratifying chRCC patients based on recurrence risk. Recently, several novel grading schemes, including three-tiered, two-tiered, and four-tiered systems, have been proposed, but their prognostic value remains controversial and lacks external validation.

Materials and methods: We included 528 patients with pathologically proven chRCC (chromophobe renal cell carcinoma) from multiple medical institutions and the Cancer Genome Atlas-Kidney Chromophobe cohort. Three experienced pathologists independently reassessed the slides based on the three novel grading schemes. Survival outcomes, including disease-specific survival (DSS), recurrence-free survival (RFS), were analyzed using Kaplan-Meier methods and Cox proportional hazards regression models. The prognostic value of the original and adjusted Leibovich risk groups was compared using Harrell's C-index.

Results: All grading systems demonstrated significant survival differences among their respective groups (p < 0.001 for all). However, within the four-tiered system, no significant survival disparity was observed between grade 1 and grade 2 tumors (GTG2 without necrosis) (p = 0.619 for DSS). When patients with necrosis were excluded, no survival difference was detected between CTG1 and CTG2 tumors in the three-tiered system (p = 0.870 for DSS), challenging the prognostic utility of distinguishing between these two grades. The adjusted Leibovich risk stratification (C-index = 0.840 for DSS), incorporating necrosis and tumor thrombus, demonstrated superior prognostic value compared to the original model (C-index = 0.762 for DSS), with more pronounced survival distinctions and improved predictive performance.

Conclusion: Our study validates the prognostic significance of recently developed grading systems for chRCC. The observed survival difference between CTG1 and CTG2 in the three-tiered system may be attributed to varying percentages of coagulative necrosis. By integrating necrosis and tumor thrombus into the Leibovich risk groups, we enhanced the model's ability to distinguish between patients and improved its predictive performance.