Differentiating Upper Tract Urothelial Carcinoma with Synchronous or Metachronous Bladder Cancer

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.