Abstract
Upper tract urothelial carcinoma (UTUC) and urinary bladder cancer (UBC), though histologically similar, differ molecularly, prompting interest in their biomarker profiles for targeted therapies like antibody-drug conjugates (ADCs) enfortumab vedotin (targeting Nectin-4) and sacituzumab govitecan (targeting TROP-2). This study investigated Nectin-4 and TROP-2 expression in 87 UTUC patients, including 54 with a history of concurrent UBC (UTUC + UBC) and 33 with UTUC alone. Immunohistochemical analysis revealed widespread TROP-2 expression (98.8% of samples), with high levels linked to low-grade UTUC (p = 0.043) and intense staining (mean H-score 227 ± 63) across both cohorts. Nectin-4 was expressed in 70.1% of samples overall but was more frequent in the UTUC + UBC group (88.8% vs. 63.6% in UTUC-only patients), though this difference lacked statistical significance (p = 0.340). Notably, Nectin-4 staining intensity was weak in both groups (mean H-score 66 ± 65), suggesting biological distinctions between UTUC with and without UBC. The findings imply that ADCs targeting TROP-2 and Nectin-4 may hold therapeutic promise in UTUC without requiring prior biomarker testing. Additionally, the elevated Nectin-4 expression in UTUC + UBC patients hints at divergent molecular pathways that could influence treatment strategies, warranting further clinical exploration.