Prognosis and tumor grading in bladder urothelial carcinomas with intratumoral grade heterogeneity

Grade heterogeneity is one of the most debated issues in the grading of urothelial carcinomas. The 2022 WHO classification states that approximately one-third of urothelial carcinomas exhibit grade heterogeneity and suggests that the presence of ≥5% high-grade component may justify classification as high-grade. Nevertheless, the need for further evidence was also emphasized. This study aimed to evaluate the prognostic impact of the high-grade component in urothelial carcinomas with grade heterogeneity and to determine a threshold value for high-grade proportion that is clinically meaningful for grading.

This retrospective study included 180 cases of non-muscle-invasive urothelial carcinoma with grade heterogeneity, diagnosed between January 2019 and August 2022 on TUR specimens, with available clinical data. Recurrence and survival time were assessed. Cases with >90% high-grade component were excluded.

Recurrence was observed in 26.7% of cases. The two-year survival rate was 73.3%. While no significant association was found between recurrence and the proportion of high-grade component, survival time significantly decreased as the proportion of high-grade component increased. ROC curve analysis identified 27.5% as the cut-off value associated with adverse prognosis.

In non-muscle-invasive urothelial carcinomas, the proportion of high-grade component showed a strong association with survival. Together with literature findings, our results suggest that a threshold higher than 5% may be more appropriate for assigning tumors to the high-grade category. Nonetheless, risk stratification incorporating tumor size and extent remains essential for prognostic evaluation.