Abstract
The features of patients with multiple urothelial tumors remain to be elucidated. We intend to differentiate primary upper tract urothelial carcinoma with synchronous urothelial bladder cancer (UTUC + sUBC) and UTUC with metachronous UBC (UTUC + mUBC) cases to determine whether these temporal patterns reflect biologically distinct processes. A subgroup analysis of a retrospective cohort of UTUC (n = 114) was performed comparing UTUC + sUBC (n = 14) with UTUC + mUBC (n = 29). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERTp, FGFR3, RAS, and TP53 status. Kaplan-Meier analyses estimated the progression-free survival (PFS) and overall survival (OS) of both UTUC subgroups, and the log-rank test was used to assess differences between subgroups. Our study reveals no significant differences in phenotype or genomic profile between synchronous and metachronous UTUC-UBC cases (p > 0.05). Nevertheless, patients with synchronous UBC revealed significantly worse outcomes in PFS (2y-PFS 23.1% vs. 52.1%, p = 0.029) and OS (2y-OS 40.4% vs. 84.4%, p = 0.016) than those with metachronous disease. These discrepancies could arise from as yet-uncharacterized molecular features or microenvironmental influences.