Stage-specific associations of HER2 overexpression with clinical and pathological features in bladder cancer: a systematic review and meta-analysis.
Citing Guo, Jinchang Wei, Yajie Wang et al.
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In 30 seconds
This PRISMA-compliant systematic review and meta-analysis pooled retrospective observational studies of treatment-naive patients with bladder urothelial carcinoma, examining HER2 overexpression by immunohistochemistry and clinicopathological features by disease stage. Across 19 studies and 2799 patients, HER2 positivity in non-muscle-invasive disease was associated with progression (risk difference [RD] 0.31, 95% CI 0.23-0.39), as well as higher stage, grade, multifocality, and recurrence. In muscle-invasive or metastatic disease, the only significant association was with lymph node metastasis (RD 0.11, 95% CI 0.03-0.19).
Key findings
- In NMIBC, HER2 overexpression was associated with progression (RD: 0.31, 95% CI: 0.23-0.39).
- In NMIBC, associations were also reported with higher T stage (RD: 0.11, 95% CI: 0.08-0.15) and higher grade (RD: 0.22, 95% CI: 0.16-0.28).
- In MIBC/mUC, HER2 overexpression was significantly associated only with lymph node metastasis (RD: 0.11, 95% CI: 0.03-0.19).
- Associations were consistent across the immunohistochemistry thresholds examined.
Why it matters
The findings suggest that HER2 overexpression may relate to different adverse features depending on bladder cancer stage: progression and other aggressive characteristics in NMIBC, and lymphatic spread in MIBC/mUC. This stage-specific pattern may inform research into biomarker-based risk stratification and targeted therapies, while the observational evidence does not establish that HER2 causes these outcomes.
What to keep in mind
The evidence came from retrospective observational cohorts, and HER2 positivity was defined using varying immunohistochemistry thresholds.