The effect of HER2 status on oncological outcomes of patients with invasive bladder cancer

Urol Oncol. 2016 Dec;34(12):533.e1-533.e10. doi: 10.1016/j.urolonc.2016.07.006. Epub 2016 Sep 21.

Abstract

Purpose: The aim of this study was to evaluate the overexpression of human epidermal growth factor receptor 2 (HER2) in patients with bladder cancer (BCa) and to assess its association with oncological outcomes.

Methods: This retrospective single-center study included 354 patients with BCa treated with radical cystectomy (RC). HER2 status was assessed with immunohistochemistry and scored according to HercepTest. Conditional survival and competing risk regression were performed to assess the association between HER2 expression and survival outcomes.

Results: HER2 was overexpressed in 36% of patients. HER2 overexpression was associated with features of tumor aggressiveness such as lymph-node metastases (P = 0.002). At a median follow-up of 123 months (interquartile range: 79-180), 160 patients (45%) experienced disease recurrence, 263 patients (74%) died and 157 (44%) died of cancer. On multivariable analyses, HER2 overexpression was not significantly associated with any oncological outcomes. Adding HER2 status to a model for the prediction of survival outcomes did not change the accuracy of the model for any of the outcomes. Interestingly, HER2 status significantly affected late disease recurrence (P = 0.05 for conditional survival at 24 months).

Conclusions: More than one third of RC patients overexpress HER2 in their tumors. HER2 overexpression was associated with features of biological and clinical aggressiveness. HER2 did not add prognostic significance to the standard established predictors of survival outcomes after RC. However, due to the high overexpression rate, it could represent a target for therapy in select advanced BCa tumors.

Keywords: Bladder cancer; HER2; Prognosis; Recurrence; Survival; Target therapy.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Transitional Cell / chemistry
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / therapy
  • Chemotherapy, Adjuvant
  • Combined Modality Therapy
  • Cystectomy
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Genes, erbB-2*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Recurrence, Local
  • Receptor, ErbB-2 / analysis*
  • Receptor, ErbB-2 / biosynthesis
  • Retrospective Studies
  • Treatment Outcome
  • Urinary Bladder Neoplasms / chemistry
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins
  • ERBB2 protein, human
  • Receptor, ErbB-2