Abstract LB-195: A double-blind randomized controlled multisite trial evaluating tissue effects of preoperative finasteride in clinically organ-confined prostate cancer: Pathologic outcomes.
Authors: Kim Jeri , Davis John W. , Klein Eric A. , Magi-Galluzzi Cristina , Lotan Yair , Ward John F. , Pisters Louis L. , Basler Joseph W. , Pettaway Curtis A. , Li Ning Tapia Elsa M. , Wang Xuemei , Do Kim-Anh , Lee Jack , Vornik Lana A. , Tangrea Joe , Parnes Howard L. , Lippman Scott M. , Thompson Ian M. , Brown Powel H. , Troncoso Patricia , Logothetis Christopher J. 
Published: August 2014

Abstract
Background: The Prostate Cancer Prevention Trial (PCPT) showed a relative reduction of 24.8% in cumulative incidence of prostate cancer (PC) in finasteride-treated men (18.4 v 24.4%; p&lt;.001). However, high-grade cancers (Gleason score [GS] ≥7) were more commonly detected in men receiving finasteride than placebo (6.4 v 5.1%; p=.005), an effect of uncertain significance. We therefore undertook a study to determine differences between finasteride-exposed and -unexposed (placebo/control) cancers in the expression of a preselected molecular signature shown to distinguish Gleason grade (GG) 3 from GG 4 untreated tumors.
Methods: This 4-site presurgical trial was in men with clinically organ-confined PC (cT1c/T2; GS 6 or 7; prostate-specific antigen [PSA] &lt;10 ng/mL) randomly assigned to treatment with 5 mg finasteride or placebo daily for 4-6 wk prior to prostatectomy. At baseline and at surgery, PSA, testosterone (T), dihydrotestosterone (DHT), estrone (E1), and estradiol (E2) levels were measured in men who opted to donate blood for research. We used a standard method to handle radical prostatectomy (RP) specimens, including mapping of tumor foci to document relevant morphologic data.
Results: In all, 210 patients consented, 204 were randomized, 183 were evaluable for detailed pathologic outcomes, and 163 were evaluable for PSA and hormone levels. Median age was 60 (45-73) yr. Median treatment time was 28 (10-43) days. Median prostate total tumor volume (TV) was 0.9 (0-10.4) cc, and peripheral zone TV, 0.6 (0-9.3) cc. Biopsy (Bx) GS, GS upgrade between Bx and RP, specimen GS/GG, total cancer foci, zonal origin of dominant cancer, and median total and PZ TV were similar in the 2 treatment arms (A v B). Post-treatment, median PSA was significantly lower (3.2 v 5.2 ng/mL; p&lt;.001); testosterone, significantly higher (391 v 325 ng/dL; p=.021); and DHT, significantly lower (10 v 27 ng/dL; p&lt;.001) in arm A than in arm B. No differences were noted in E1 and E2 levels. Biomarker analysis of a preselected molecular signature is under way; unblinding awaits completion of biomarker analysis.
Conclusions: No significant difference in GS distribution was observed between the two groups after short-term exposure to finasteride or placebo. Modulation of PSA, T, and DHT levels occurred in a statistically significant uneven distribution by study arm. Molecular signature characterization has been completed, and the planned analysis of associations is under way. The findings are expected to provide insight into the reported grade effect attributed to finasteride. (This work was supported in part by NCI contract N01-CN-35159.)
Citation Format: Jeri Kim, John W. Davis, Eric A. Klein, Cristina Magi-Galluzzi, Yair Lotan, John F. Ward, Louis L. Pisters, Joseph W. Basler, Curtis A. Pettaway, Elsa M. Li Ning Tapia, Xuemei Wang, Kim-Anh Do, Jack Lee, Lana A. Vornik, Joe Tangrea, Howard L. Parnes, Scott M. Lippman, Ian M. Thompson, Powel H. Brown, Patricia Troncoso, Christopher J. Logothetis. A double-blind randomized controlled multisite trial evaluating tissue effects of preoperative finasteride in clinically organ-confined prostate cancer: Pathologic outcomes. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-195. doi:10.1158/1538-7445.AM2013-LB-195