Prognostic Significance of HER2 Expression in Patients with Bacillus Calmette-Guérin–exposed Non–muscle-invasive Bladder Cancer

BACKGROUND: Guidelines recommend intravesical instillation of bacillus Calmette-Guérin (BCG) as the first-choice treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC). However, there is no therapeutic biomarker for predicting BCG efficacy, especially in high-risk cases with high failure rates. HER2 expression is considered a prognostic factor for bladder cancer. OBJECTIVE: To elucidate the predictive value and significance of HER2 expression in patients with BCG-exposed NMIBC. DESIGN, SETTING, AND PARTICIPANTS: CFU, strain D2PB302) 2-6 wk after transurethral resection of bladder tumor and received 19 treatments over a period of 1 yr. HER2 immunohistochemistry (IHC) results available for 314 patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcomes investigated were recurrence-free survival (RFS) and progression-free survival (PFS). Outcome relationships were explored using multivariable Cox regression and log-rank analysis. RESULTS AND LIMITATIONS: In the IHC population, 35.7% of patients had HER2 overexpression (IHC score 2/3+). This group had a poor 5-yr RFS rate of 16.5%, in comparison to 68.0% in the group with low HER2 expression (p < 0.001). Patients with high-risk NMIBC and HER2 overexpression had the highest risk of BCG treatment failure, with 5-yr RFS and PFS rates of 19.0% and 58.2%, respectively. Conversely, HER2-negative (IHC score 0) patients with high-risk NMIBC experienced a long-term BCG benefit, with 5-yr RFS and PFS rates of 80.8% and 92.1%, respectively. Limitations include the retrospective study design and the limited details regarding BCG use. CONCLUSIONS: HER2 was an independent predictor of poor BCG efficacy in NMIBC. Patients with high-risk NMIBC and HER2 overexpression had the highest risk of disease recurrence and progression after exposure to BCG. Anti-HER2 targeted therapies could be considered for these patients. PATIENT SUMMARY: Measurement of blood levels of the protein HER2 can be used to predict outcomes after BCG (bacillus Calmette-Guérin) bladder therapy for patients with intermediate- or high-risk non-muscle-invasive bladder cancer. Measurement results for HER2 may help in guiding personalized treatment for these patients.