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Preoperative Plasma HER2 and Epidermal Growth Factor Receptor for Staging and Prognostication in Patients with Clinically Localized Prostate Cancer

Authors' Affiliations: ¹ Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas and ² Cancer Prognostics and Health Outcomes Unit, University of Montreal, Montreal, Quebec, Canada

Requests for reprints: Shahrokh F. Shariat, Department of Urology, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9110. Phone: 469-363-8500; Fax: 214-648-8786; E-mail: Shahrokh.Shariat{at}UTSouthwestern.edu.

Purpose: Human epidermal growth factor receptor-2 (HER2) and epidermal growth factor receptor (EGFR) expression have been associated with disease progression in patients with prostate cancer. We tested the hypothesis that plasma levels of HER2 and/or EGFR are associated with prostate cancer stage and prognosis in patients with clinically localized disease.

Experimental Design: We measured preoperative plasma HER2 and EGFR levels using commercially available ELISAs on banked plasma from 227 patients treated with radical prostatectomy and bilateral lymphadenectomy for clinically localized prostate adenocarcinoma.

Results: Median preoperative plasma EGFR and HER2 levels were 31.4 ng/mL (interquartile range, 19.2 ng/mL) and 10.0 ng/mL (interquartile range, 2.7 ng/mL), respectively. HER2 was elevated in patients with seminal vesicle invasion (P = 0.033). In separate multivariate analyses that adjusted for the effects of standard preoperative predictors, lower EGFR, higher HER2, and higher HER2/EGFR ratio were associated with prostate-specific antigen (PSA) progression (P = 0.003, P < 0.001, and P < 0.001, respectively). In separate multivariate analyses that adjusted for the effects of standard postoperative predictors, lower EGFR and higher HER2/EGFR ratio were associated with PSA progression (P = 0.027 and P < 0.001, respectively). Among the patients who experienced PSA progression, HER2 was significantly higher (P = 0.023) and EGFR was lower (P = 0.04) in those with features of aggressive disease (i.e., development of metastasis, PSA doubling time <10 months, and/or failure to respond to local salvage radiation therapy).

Conclusion: Preoperative plasma HER2 and EGFR were associated with prostate cancer progression after radical prostatectomy. Plasma HER2 and EGFR may provide a tool for predicting long-term recurrence-free survival and early metastasis.