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

Xingliang Tan; Zhicheng Liu; Taonong Cai; Yanjun Wang; Zhiming Wu; Zike Qin; Zhiyong Li; Zhenhua Liu; Gangjun Yuan; Qianghua Zhou; Kai Yao

doi:10.1016/j.euo.2023.10.003

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

Eur Urol Oncol. 2023 Oct 24:S2588-9311(23)00219-5. doi: 10.1016/j.euo.2023.10.003. Online ahead of print.

Authors

Affiliations

¹ Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
² Department of Urology Oncological Surgery, Chongqing University Cancer Hospital, Chongqing, China; Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China. Electronic address: yuangj@cqu.edu.cn.
³ Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Electronic address: zhouqh28@mail.sysu.edu.cn.
⁴ Department of Urology, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in Southern China, Guangzhou, China; Collaborative Innovation Center of Cancer Medicine, Guangzhou, China. Electronic address: yaokai@sysucc.org.cn.

PMID: 37884420
DOI: 10.1016/j.euo.2023.10.003

Abstract

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: A total of 454 patients with NMIBC were included. All patients started BCG intravesical instillation (1.2 × 10⁸ 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.

Keywords: Bacillus Calmette-Guérin; HER2; Intravesical instillation; Non–muscle-invasive bladder cancer; Recurrence.