Epidermal Growth Factor Receptor Cell Expression During Adjuvant Treatment After Transurethral Resection for Non-Muscle-Invasive Bladder Cancer: A New Potential Tool to Identify Patients at Higher Risk of Disease Progression - Beyond the Abstract

Patients harboring Non-Muscle-Invasive Bladder Cancer (NMIBC) have a highly variable course depending on several tumors- and patient-related factors. The high-risk disease is burdened by a significant rate of recurrence and progression despite the use of intravesical treatments following transurethral resection of bladder tumor (TURBT). On the other hand, early radical cystectomy is often delayed in NMIBC despite the unresponsiveness to BCG-adjuvant treatment. As a consequence, the choice between conservative management and aggressive surgery in high-risk tumors remains uncertain. Indeed, it is unequivocal that, to date, we are still unable to correctly and timely recognize those patients harboring a clinically unfavorable disease and more likely to develop worse outcome after deferred cystectomy. To this regard, an improvement of tools to define unequivocal selection criteria to identify those NMIBC patients at higher risk of disease progression is still needed. Next-generation sequencing technologies are developing a molecular landscape revealing novel prognostic biomarkers and molecular targets. Epidermal Growth Factor Receptor (EGFR) is a biomarker that, among many others, may select those patients more likely to develop worse oncologic outcomes and pave the way to novel selective agents ensuring for better therapeutic responses.

In our preliminary experience, our group investigated the feasibility and prognostic value of sequential measurement of EGFR urothelial cell expression in bladder washing samples after TURBT of 58 NMIBC patients and during and after adjuvant intravesical therapy. An adequate cellular pellet to evaluate EGFR expression was obtained in more than 85% of patients’ and controls’ bladder washings, confirming the feasibility of EGFR serial evaluation. Interestingly, EGFR evaluation in bladder washings allowed the identification of a subgroup of high-risk patients characterized by EGFR cell overexpression persisting after adjuvant therapy [Figure 1]. Moreover, patients harboring high-risk NMIBC and showing EGFR overexpression had a significantly lower recurrence-free survival, progression-free survival, and cancer-specific survival. At multivariable analysis, EGFR overexpression was confirmed as an additional independent prognostic factor to the EORTC scoring system of disease recurrence and progression. These observations could indicate a subgroup of patients characterized by a bladder urothelium predisposed to respond to the proliferative action of EGF and unresponsive to adjuvant intravesical therapy. Moreover, overexpression of EGFR on the urothelial surface might represent a marker of biological aggressiveness and predictable lower response rate to adjuvant therapy after TURBT.


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Figure 1: Median EGFR expression (measured as folds of change) observed in 18 and 22 high-risk patients with increasing or stable/decreasing EGFR expression trend respectively after adjuvant treatment.

However, further studies with wider cohorts of high-risk NMIBC patients and with longer follow-up data are needed to confirm these results. If the role of EGFR in NMIBC oncologic outcomes will be confirmed, its evaluation in bladder washing could represent an additional parameter to the current clinical tools to dynamically predict patients’ outcome on conservative strategy and provide an individualized risk stratification. Furthermore, the identification of a biological marker involved in tumor proliferation and progression could pave the way to the introduction of novel selective agents ensuring for better therapeutic responses in BCG unresponsive patients.

Written by: Fabrizio Di Maida, MD, Department of Urology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy

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