Changes in ki-67 and cleaved caspase-3 (CC3) with short term androgen deprivation therapy (ADT) prior to prostatectomy as part of a trial in intermediate and high-risk prostate cancer (PC).

Abstract

e17502 Background: Ki-67 and CC3 are markers of cellular proliferation and apoptosis and have been associated with prognosis in localized PC. Testosterone suppression promotes a time-dependent modulation of these indices. We explored changes in Ki-67 and CC3 at different timepoints in a pilot trial using short-term ADT prior to radical prostatectomy (RP). Methods: Pts with intermediate and high-risk localized PC were randomized to receive a single dose of neoadjuvant degarelix (240 mg SC) either 4 ± 1 days (Cohort A) or 7 ± 1 days (Cohort B) prior to RP. Anatomically matched tumor foci from the pre-treatment diagnostic biopsy and the prostatectomy specimens were assessed by immunohistochemistry (IHC) for Ki-67, CC3, and PTEN expression. Results: 32 pts were randomized: 15 to Cohort A and 17 to Cohort B. Ki-67 and CC3 expression in the pre- and post-treatment samples for both cohorts are summarized in the table. A significant reduction in Ki-67 and increase in CC3 expression occurred in both cohorts (all p-values < 0.05). No difference was found when the absolute difference of Ki-67 expression was compared between Cohort A and Cohort B (p = 0.7). A significant reduction of Ki-67 and increase in CC3 expression occurred in pts independent of PTEN status. Conclusions: A reduction of Ki-67 and an increase in CC3 expression was achieved in both cohorts following a single dose of degarelix within 1 week of RP. Although loss of PTEN has been associated with androgen-independent progression, reduction of proliferation and increase in apoptosis levels were achieved independent of PTEN status in this small cohort. Further analyses are ongoing to correlate the pathologic findings with clinical outcomes. Clinical trial information: NCT01542021 . [Table: see text]