Editorial Comment

Abstract

Epidermal growth factor receptor (EGFR) is expressed in nonsmall cell lung cancer, head and neck squamous cell carcinoma, colorectal cancer, and breast cancer. In each of these diseases, there are EGFR inhibitors that are approved for these conditions. EGFR is expressed in squamous cell penile cancer.1Barnholtz-Sloan J.S. Maldonado J.L. Pow-sang J. Giuliano A.R. Incidence trends in primary malignant penile cancer.Urol Oncol. 2007; 25: 361-367Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar, 2Bahl A.K. Sohail M. Johnson D. et al.EGFR overexpression in invasive squamous cell carcinoma of the penis.J Clin Onc. 2010; 28 (ASCO proceedings): e15078Google Scholar, 3Gou H.-F. Li X. Qiu M. et al.Epidermal growth factor receptor (EGFR)-RAS signaling pathway in penile squamous cell carcinoma.PLoS ONE. 2013; 8: e62175Crossref PubMed Scopus (39) Google Scholar The question: is it potentially useful in patients with squamous cell penile cancer? There are important parameters whether a target for treatment is important or not. Is the target over expressed, could it be inhibited, is it the predominant target, is it an important factor for growth for this cancer, and could it be given safely. There are more questions than answers. Gou et al3Gou H.-F. Li X. Qiu M. et al.Epidermal growth factor receptor (EGFR)-RAS signaling pathway in penile squamous cell carcinoma.PLoS ONE. 2013; 8: e62175Crossref PubMed Scopus (39) Google Scholar in a study of 150 patients in China with penile cancer showed EGFR expression was positive in all the 150 cases. Five cases (3.3%) were 1+, 7 (4.7%) were 2+, 21 (14%) were 3+, and 117 (78%) were 4+. The rate of EGFR over expression was 92%. No significant correlation was observed between the EGFR expression and tumor grade (P = .215), pT stage (P = .053), or lymph node metastases (P = .685). In a study by Lavens et al4Lavens N. Gupta R. Wood L.A. EGFR overexpression in squamous cell carcinoma of the penis.Curr Oncol. 2010 February; 17: 4-6PubMed Google Scholar from a selected 8-year time period, 17 cases were obtained and studied. The median age of all patients was 66 years (range, 46-95). All 17 cases over expressed EGFR. Expression was 3+ in 14 cases and 2+ in 3 cases. The case series highlights the importance of reviewing the biology of the disease and the importance of identifying markers that are expressed. Two of the 3 patients responded to the treatment, and 1 had a response lasting 42 months. Several investigators have shown that patients with EGFR expression in small case series also did respond to EGFR inhibitors. On the basis of these preliminary data, I agree with the authors that a clinical trial should be done. In addition, it is important to develop less toxic oral therapy for penile cancer because chemotherapy can be toxic especially for patient with advanced cancer, and additionally there are no options after tumor progression on cisplatin-based treatment. To test the question whether EGFR inhibitors are effective in the treatment of this cancer, there is an ongoing trial of Dacomitinib (PF-00299804 pan HER inhibitor/EGFR) in advanced/metastatic squamous cell carcinoma of the penis with the primary endpoint of response rate. NCT01728233 was based on early results from Tumori Milan and the University of Texas MD Anderson.5Clinical Trials.gov 2013 NCT identifier number 01728233.Google Scholar This might be the next step big for this cancer. Epidermal Growth Factor Receptor-targeted Therapy in Squamous Cell Carcinoma of the Penis: A Report of 3 CasesUrologyVol. 83Issue 1PreviewTo describe 3 cases of advanced refractory penile cancer treated with targeted therapy against the epidermal growth factor receptor (EGFR). Full-Text PDF ReplyUrologyVol. 83Issue 1PreviewAs the editorial comment points out, the gap between our knowledge of which markers are expressed on tumor cells and which of these markers will provide a successful therapeutic target has become increasingly apparent. Furthermore, the complexities of signaling pathways have complicated attempts to target receptors identified on tumor tissue: for example, K-ras mutations affect response to epidermal growth factor receptor (EGFR)–targeted therapy. In penile cancer, with nearly ubiquitous EGFR expression and low incidence of K-ras mutation, we might expect some response to EGFR-targeted therapy but will need to interrogate the pathway more comprehensively to understand why some patients benefit and others do not. Full-Text PDF