Human epidermal growth factor receptor 2 expression is more important than Bacillus Calmette Guerin treatment in predicting the outcome of T1G3 bladder cancer.

Luigi Cormio,Vincenzo Pagliarulo,Maria Carmela Pedicillo,Giuseppe Calò,Paolo Massenio,Giuseppe Carrieri,Simona Cagiano,Pantaleo Bufo,Francesca Sanguedolce,Antonella Cormio

doi:10.18632/oncotarget.15989

Abstract

In the present study we tested the role of Human Epidermal Growth Factor Receptor-2 (HER-2) expression, as assayed by immunohistochemistry, in predicting recurrence and progression in 67 patients with T1G3 BC having undergone transurethral resection of bladder tumor (TURBT) alone (33) or TURBT + Bacillus Calmette Guerin (BCG) instillations (34). All patients had a negative restaging TURBT within 4 months after the first TURBT. At median follow-up of 75.7 months, the overall disease-free and progression-free rates were 35.8% and 73.0%, respectively. Univariate Kaplan-Meier survival analysis showed that traditional prognostic factors (sex, tumor number/size/recurrence) failed to predict disease-free and progression free survival (DFS, PFS). BCG treatment was a significant predictor of DFS (p=0.0231) but not of PFS (p=0.6901). HER-2 overexpression was a significant predictor of DFS (p=0.0013) and PFS (p=0.0322) in the overall patients population, but failed to predict PFS when patients were stratified for treatment (BCG: p=0.1290; no BCG: p=0.1696) probably due to the limited number of events. Multivariate Cox proportional-hazards regression analysis confirmed that BCG treatment was a significant predictor of DFS (p=0.012) but not of PFS (p=0.924), whereas HER-2 overexpression was a significant predictor of DFS (p=0.001) and PFS (p=0.041). These findings suggest that HER-2 status performs better than “traditional” prognostic factors as well as of BCG treatment in predicting the outcome of T1G3 BC, thus providing grounds for further testing this marker and possibly incorporating it in a panel of molecular markers that could reliably predict the behavior of this challenging disease.

Highlights

Bladder cancer (BC) is the fourth most common cancer in men in the US with an incidence of 20.3 per 100000 in both sexes [1]
Multivariate Cox proportional-hazards regression analysis confirmed that Bacillus Calmette Guerin (BCG) treatment was a significant predictor of DFS (p=0.012) but not of progressionfree survival (PFS) (p=0.924), whereas Human Epidermal Growth Factor Receptor-2 (HER-2) overexpression was a significant predictor of DFS (p=0.001) and PFS (p=0.041)
These findings suggest that HER-2 status performs better than “traditional” prognostic factors as well as of BCG treatment in predicting the outcome of T1G3 BC, providing grounds for further testing this marker and possibly incorporating it in a panel of molecular markers that could reliably predict the behavior of this challenging disease

Summary

Introduction

Bladder cancer (BC) is the fourth most common cancer in men in the US with an incidence of 20.3 per 100000 in both sexes [1]. In the EU, the age-standardised incidence rate is as high as 16.3 [2]. Muscle invasive BC (MIBC) accounts for 20-25% of newly diagnosed cases of BC whereas the remaining present as non muscle invasive BC (NMIBC); over 50% of NMIBCs recur, while 15-20% advance towards a muscle-invasive form [3]. High-grade (previously G3) stage T1 (T1G3) BC is considered the most challenging form of NMIBC due to its www.impactjournals.com/oncotarget high propensity to recur and progress to muscle invasive disease. Long-term progression and death rates as high as 53% and 34%, respectively, have been reported [4]. T1G3 has an unpredictable behaviour as one third of patients never recur or progress, one third requires deferred cystectomy and another third eventually dies of this disease independently on given treatment [5]. The identification of factors predicting disease behaviour represents a major clinical issue

Methods

Results

Conclusion