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



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.



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).



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.
Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Surgical Sciences, San Giovanni Battista Hospital, University of Studies of Torino, Turin, Italy.
Francesco
F
Soria
Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Urological Research Institute, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.
Marco
M
Moschini
Department of Pathology, Medical University of Vienna, Vienna, Austria.
Andrea
A
Haitel
Department of Urology, Medical University of Vienna, Vienna, Austria; Geneva Cancer Registry, Global Health Institute, University of Geneva, Geneva, Switzerland.
Gregory J
GJ
Wirth
Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
Kilian M
KM
Gust
Department of Urology, Urological Research Institute, San Raffaele Scientific Institute, Vita-Salute University, Milan, Italy.
Alberto
A
Briganti
Department of Urology, Pitié-Salpétrière, Assistance-Publique Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris VI, Paris, France.
Morgan
M
Rouprêt
Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.
Tobias
T
Klatte
Department of Urology, Medical University of Vienna, Vienna, Austria.
Melanie R
MR
Hassler
Department of Urology, University of Montreal, Montreal, Canada.
Pierre I
PI
Karakiewicz
Department of Urology, Medical University of Vienna, Vienna, Austria; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Shahrokh F
SF
Shariat
D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D015653:Cystectomy; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D018734:Genes, erbB-2; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis* / Q000096:biosynthesis; D009364:Neoplasm Recurrence, Local; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000096:biosynthesis; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000628:therapy
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
Bladder cancer; HER2; Prognosis; Recurrence; Survival; Target therapy