Functional heterogeneity of prostatic intra-epithelial neoplasia: Length of hormonal therapy influences response

Abstract

4648 Background: Prostatic intraepithelial neoplasia (PIN) is a premalignant lesion of the prostate etiologically linked to prostate cancer. While androgen deprivation therapy (ADT) has been used to reduce prostate cancer, there are controversial data regarding the effect of ADT on PIN. We hypothesized that PIN is a heterogeneous entity with respect to hormone responsiveness, that this may explain aspects of the heterogeneity in the natural history of this disease, and have used the clinical model of ADT followed by radical prostatectomy as a test of this hypothesis. Methods: We performed a retrospective study on a cohort of patients who underwent prostatectomy with biopsy proven prostate cancer. Study patients were those who must have received at least 3 months of ADT at the discretion of their surgeons. Patients from the same cohort who did not undergo ADT were used as controls. Patients were randomly selected from the database and their pathology slides were reviewed by a blinded pathologist looking for presence of PIN with an independent observer. Fisher’s exact test was used to compare the proportions of subjects who had residual PIN in the study group and the control group. Exact logistic regression was used to evaluate the duration of ADT in PIN regression. Results: Eighteen patients initially diagnosed with PIN who did not receive hormonal therapy were identified; 28 patients with PIN who underwent hormonal therapy were also studied. All patients who did not receive hormonal therapy had residual PIN whereas 7 of 28 patients undergoing ADT had no residual PIN (p = 0.043). Evaluation of hormonal therapy between responders and non-responders showed statistically significant association between PIN regression and hormone therapy duration (p < 0.001). However PIN response to ADT was not uniform as 16% of patients with ADT longer than 6 months had residual PIN, suggesting variable sensitivity of PIN to ADT. Conclusions: Our results demonstrate that ADT does cause PIN regression, and that there is heterogeneity in this effect with respect to hormonal duration. We propose for future prospective, multi-centered, randomized trials in which ADT impact on PIN is characterized further. No significant financial relationships to disclose.