E-Cadherin Protein Expression Predicts Prostate Cancer Salvage Radiotherapy Outcomes

Abstract

Radiotherapy for biochemical prostate cancer recurrence after prostatectomy achieves durable salvage rates of only 40% to 50%. Improved methods of identifying patients unlikely to benefit from salvage radiotherapy are needed. Altered expression of the adhesion molecule E-cadherin may be associated with the invasive and metastatic phenotype. We examined the relationship between E-cadherin expression and outcomes after salvage radiotherapy. E-cadherin expression was examined by immunohistochemistical analysis of a tissue microarray of prostatectomy tissues from patients who underwent salvage radiotherapy. The relation between E-cadherin staining, other risk factors and biochemical failure after salvage radiotherapy was analyzed using Kaplan-Meier and Cox regression methods. Of 37 analyzable cases 25 showed aberrant E-cadherin expression, while the remainder had normal expression. At a median clinical followup of 40 months univariate analysis demonstrated that E-cadherin staining was not associated with Gleason score, extracapsular extension, surgical margin status, pre-prostatectomy or pre-radiotherapy prostate specific antigen, complete biochemical response after radiotherapy or adjunctive hormonal therapy but it was associated with seminal vesicle invasion. Two-year failure-free survival was 55% in patients with aberrant E-cadherin expression compared with 92% in patients with normal E-cadherin expression (p = 0.02). Multivariate analysis confirmed that aberrant E-cadherin expression was associated with salvage radiotherapy failure (p = 0.03). Aberrant E-cadherin staining is associated with increased biochemical failure rates after salvage radiotherapy. Patients with biochemical failure after prostatectomy and aberrant E-cadherin expression are likely to have subclinical disseminated disease. Early systemic therapy may be warranted in these patients.