A Molecular Pathologic Framework for Risk Stratification of Stage T1 Urothelial Carcinoma

Area of Science:

• Oncology
• Urothelial Carcinoma Research
• Cancer Biomarkers

Background:

• One-third of stage T1 urothelial carcinoma (UC) cases progress to muscle-invasive disease, necessitating better risk stratification tools.
• Accurate identification of high-risk T1 UC is crucial for timely intervention and improved patient outcomes.

Purpose of the Study:

• To evaluate the utility of molecular pathologic subtypes in improving the risk stratification of stage T1 UC.
• To determine if classifying T1 UC into urobasal (Uro), genomically unstable (GU), and squamous-cell-carcinoma-like (SCCL) subtypes enhances prediction of tumor progression.

Main Methods:

• A cohort of 167 primary stage T1 UCs was characterized using immunohistochemistry.
• Tumors were classified into Uro, GU, and SCCL molecular subtypes.
• Progression-free survival was analyzed using univariate and multivariate models, with validation using additional markers and mRNA expression.

Main Results:

• The molecular subtypes Uro, GU, and SCCL were identified in a population-based cohort.
• Progression risk was low for Uro tumors and high for GU/SCCL tumors.
• Clinical risk factors and progression biomarkers were strongly associated with GU/SCCL subtypes.

Conclusions:

• Molecular subtype classification improves the identification of progressing stage T1 UC tumors.
• GU and SCCL subtypes are associated with a higher risk of progression and are linked to specific clinical risk factors.
• This classification provides a more refined approach to managing stage T1 UC.