Tumor cell proliferation in prostate cancer after 3 months of neoadjuvant LHRH analogue treatment is a prognostic marker of recurrence after radical prostatectomy

Abstract

Objectives. To evaluate tumor cell proliferation in relation to histopathologic regressive changes and failure after radical prostatectomy after a 3-month course of neoadjuvant luteinizing hormone-releasing hormone (LHRH) analogue treatment. Methods. We evaluated slides from 103 radical prostatectomy specimens of the 111 patients participating in a randomized trial of a 3-month course of neoadjuvant LHRH analogue treatment before radical retropubic prostatectomy (n = 50) versus surgery alone (n = 53). The histopathologic regressive changes in the specimens were scored by two pathologists. Sections were stained with the anti-Ki-67 monoclonal antibody MIB-1. The proliferation index (PI) was defined as the proportion of Ki-67-positive cells in a random cell count. The patients were followed up until treatment failure or for a mean of 39 months among those without failure. Results. In the neoadjuvant group, increasing histopathologic regressive changes correlated with a decrease in capsular penetration, positive surgical margins, and tumor cell proliferation but did not correlate with Gleason score in biopsies. Treatment failure was not related to the histopathologic regressive changes. In the neoadjuvant treatment group, progression-free survival was longer in the subgroup of patients with tumors with a PI less than 1.2% compared with those with tumors with a PI greater than 1.2% ( P = 0.02). Multivariate analysis of PI and histopathologic and clinical features showed the PI ( P = 0.002) and the pretreatment serum prostate-specific antigen level ( P = 0.003) to be significant prognostic markers of failure in the neoadjuvant group. Conclusions. Tumor cell proliferation after 3 months of neoadjuvant hormonal treatment is a prognostic marker of failure after radical prostatectomy without correlation to Gleason score or the histopathologic regressive changes resulting from hormonal treatment.