The biologic and prognostic value of tumor human epidermal growth factor receptor 2 (HER2) expression in patients with advanced urothelial carcinoma (UC) who undergo systemic therapies remains controversial. A systematic search of English-language literature using PubMed, Scopus, and Cochrane Library was performed in October 2025 according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) protocol to evaluate the prognostic value of tumor HER2 expression in predicting oncological outcomes of patients with advanced UC. The primary endpoints were recurrence-free survival (RFS), progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). Seventeen studies comprising 4909 patients were eligible. HER2 expression was significantly associated with inferior RFS (HR 1.68, 95% CI 1.16–2.42; p = 0.005) and CSS (HR 1.36, 95% CI 1.10–1.68; p = 0.004), but not with OS (HR 1.03, 95% CI 0.54–1.80) or PFS (HR 0.97, 95% CI 0.50–1.89), in patients with advanced UC. In conclusion, tumor HER2 expression may identify a subgroup of patients with advanced UC at increased risk of recurrence and cancer-specific mortality, supporting its potential role as a prognostic biomarker. However, standardized assessment and prospective studies are warranted to define its utility for risk stratification and therapeutic targeting.
Alibeiginejad et al. (Tue,) studied this question.