Xuejian Yang, Lingkai Cai, Chenghao Wang, Zhengye Tan, Chang Chen, Yiran Tao, Yuheng Zhang, Meiling Bao, Hao Yu, Qiang Cao, Yashi Ruan, Qiang Lu, Xiao Yang
High HER2 expression is an independent risk predictor of recurrence in NMIBC patients. It provides significant incremental prognostic value beyond EORTC and CUETO risk scores and enhances risk stratification within intermediate- and high-risk EAU groups.
BACKGROUND/OBJECTIVES: The available risk stratification models used to predict the prognosis of non-muscle-invasive bladder cancer (NMIBC) are not efficient enough. The research focused on assessing the relationship between HER2 expression status and recurrence in NMIBC.
METHODS: The retrospective study consisted of 217 NMIBC patients who were treated by transurethral resection of bladder tumor. Immunohistochemistry (IHC) was used to evaluate HER2 expression as being high (IHC 2+/3+) or low (IHC 0/1+). The relationship between the clinicopathological characteristics and the recurrence-free survival (RFS) was examined through the use of both univariate and multivariate Cox proportional hazards regression. The additional predictive utility of HER2 to the European Organization for Research and Treatment of Cancer (EORTC) and Club Urológico Español de Tratamiento Oncológico (CUETO) models was determined based on the concordance index (C-index) and time-dependent area under the receiver operating characteristic curve (t-AUC).
RESULTS: The patients who had high HER2 expression (n = 96) had significantly increased rates of pT1 stage (39.6% vs. 18.2%, P < .001), high-grade tumor (75.0% vs. 44.6%, P < .001), and recurrent tumor (29.2% vs. 13.2%, P = .004) when compared to the low-expression group. Multivariate analysis identified high HER2 expression as an independent predictor of recurrence (HR 2.58, 95% CI, 1.41-4.73; P = .002). HER2-high patients had significantly worse RFS. Subgroup analyses showed worse RFS for HER2-overexpressing tumors across intravesical instillation subgroups and within the European Association of Urology (EAU) intermediate- and high-risk groups (all P < .05). Integrating HER2 status significantly improved the predictive performance of both the EORTC (C-index: 0.703-0.730) and CUETO models (C-index: 0.687-0.716).
CONCLUSION: High HER2 expression is an independent risk predictor of recurrence in NMIBC patients. It provides significant incremental prognostic value beyond EORTC and CUETO risk scores and enhances risk stratification within intermediate- and high-risk EAU groups.