Interstitial fibrosis in radical prostatectomy specimen treated with neoadjuvant therapy and its relationship to biochemical outcome and castration-resistant status in high-risk prostate cancer.

251 Background: Interstitial fibrosis (IF) have been known to occur in radical prostatectomy specimens treated with hormonal therapy. We previously reported that neoadjuvant therapy for high-risk prostate cancer (Pca) with luteinizing hormone-releasing hormone (LHRH) agonist and low-dose estramustine phosphate (EMP) (LHRH + EMP) significantly improved biochemical recurrence (BCR) free survival. In this study, we quantified IF in radical prostatectomy specimens treated with neoadjuvant LHRH + EMP, and we examined whether degree of IF has impact on BCR free survival or subsequent castration-resistant status. Methods: High-risk Pca was defined by the D’Amico stratification system. A total of 103 patients with high-risk Pca were enrolled in this study from July 2005 to August 2010. The LHRH + EMP therapy included the administration of the LHRH agonist and 280 mg/day of EMP for six months before the radical prostatectomy. BCR was defined as the prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after the prostatectomy. Castration-resistant prostate cancer (CRPC) is defined by PSA or radiographic progression in the castrate levels of testosterone (< 50 ng/dL). A quantitative analysis of IF was performed using computer-assisted imaging. Results: The average patient age was 67.2 (49 to 78), and the median initial PSA level was 18.8 ng/mL (4.2–95.6). All patients completed six months of LHRH + EMP neoadjuvant therapy with no delays in the radical prostatectomy. At a median follow-up period of 64.0 months, BCR occurred in 41 patients (39.8%) and CRPC occurred in nine patients (8.7%). The average IF rate was 0.43 (0.33–0.55). The five year BCR-free survival rates for the groups with IF rates less than 0.42 and greater than 0.42 were 74.7% and 50.0%, respectively. The log-rank test was significantly different between the two groups (p = 0.010). We could not identify CRPC in the patients with IF rates less than 0.42. Conclusions: Although the present study was small and preliminary, the IF rate may have a predictive potential for biochemical outcome and the occurrence of CRPC after neoadjuvant therapy for high-risk Pca. Further study is warranted to elucidate its clinical significance.