HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study

Introduction: Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2(+)) on the prognosis of muscle-invasive bladder cancer (MIBC). Materials and methods: This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically nonmetastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. Results: Among the 61 patients with d-MIBC, 14 were HER2(+) and 47 HER2(-). Age less than 70 years [hazard ratio (HR): 0.312, CI: 0.16-0.59, P<0.001] and HER2(+) status (HR: 0.40, CI: 0.19-0.85, P=0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2(+) status was a significant predictive factor for the pT2 stage (HR): 36.8, CI: 4.83-797.41, P<0.01). Age less than 70 years (HR: 0.15, CI: 0.05-0.42, P<0.001) and HER2(+) status (HR: 0.11, CI: 0.02-0.54, P=0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. Conclusions: HER2(+) status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2(+) status not only consistently predicted a favorable T stage after RC, but also predicted better survival than pathological outcomes.