Epidermal Growth Factor Receptor (EGFR) 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

Fabrizio Di Maida; Andrea Mari; Cristina Scalici Gesolfo; Antonina Cangemi; Rosalinda Allegro; Simone Sforza; Andrea Cocci; Riccardo Tellini; Lorenzo Masieri; Antonio Russo; Marco Carini; Andrea Minervini; Vincenzo Serretta

doi:10.1016/j.clgc.2019.04.008

Epidermal Growth Factor Receptor (EGFR) 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

Clin Genitourin Cancer. 2019 Aug;17(4):e751-e758. doi: 10.1016/j.clgc.2019.04.008. Epub 2019 Apr 26.

Affiliations

¹ Department of Urology, University of Florence, Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, Florence, Italy.
² Section of Urology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy.
³ Section of Medical Oncology, Department of Surgical, Oncological, and Stomatological Sciences, University of Palermo, Palermo, Italy.
⁴ Department of Statistics, University of Palermo, Palermo, Italy.
⁵ Section of Urology, Department of Surgical, Oncological and Stomatological Sciences, University of Palermo, Palermo, Italy. Electronic address: vincenzo.serretta@unipa.it.

PMID: 31126772
DOI: 10.1016/j.clgc.2019.04.008

Abstract

Background: The aim of the study was to investigate the feasibility of Epidermal Growth Factor Receptor (EGFR) measurement in bladder washings of patients affected by non-muscle-invasive bladder cancer (NMIBC) and its prognostic role in identifying risk subgroups and predicting disease recurrence and progression.

Patients and methods: Patients with NMIBC treated with transurethral resection of bladder tumor (TURBT) from 2012 to 2015 were enrolled. Samples of bladder washings were collected and stored at -80°C until RNA extraction. The cDNA obtained from RNA was used to perform a gene expression analysis by a real time polymerase chain reaction.

Results: An adequate cellular pellet was obtained in 50 (86.2%) of 58 patients and in 18 (85.7%) of 21 controls. Patients had a median 2.5-, a 1.6- and a 2.8-fold EGFR expression compared with controls before, during, and after adjuvant treatment, respectively. Patients at higher risk had a significantly higher EGFR expression compared with patients at low and intermediate risk when EGFR was measured during (P = .04) and after (P = .001) adjuvant therapy. At a median follow-up of 35.5 months (interquartile range, 19.0-54.8 months), in the high-risk group, patients with overexpression had a significantly lower recurrence-free survival (27.9% vs. 58%), progression-free survival (75.9% vs. 90.2%), and cancer-specific survival (77.7% vs. 93.3%). At multivariable analysis, EGFR overexpression was an additional independent prognostic factor to the European Organisation for Research and Treatment of Cancer scoring system of disease recurrence (hazard ratio, 1.98; 95% confidence interval, 1.32-2.97) and progression (hazard ratio, 1.84; 95% confidence interval, 1.27-2.65).

Conclusions: EGFR overexpression might represent an additional parameter to the current clinical tools for an individualized risk stratification.

Keywords: Biomarker; Bladder washing; Epidermal Growth Factor Receptor (EGFR); Molecular classification; Non-Muscle Invasive Bladder Cancer (NMIBC).

MeSH terms

Administration, Intravesical
Aged
Chemotherapy, Adjuvant / methods*
Cystectomy / methods*
Disease Progression
ErbB Receptors / genetics
Feasibility Studies
Female
Gene Expression Regulation, Neoplastic
Humans
Male
Prognosis
Treatment Outcome
Up-Regulation*
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / therapy*

Substances

EGFR protein, human
ErbB Receptors