Abstract 3952: Recurrent prostate cancer genomic alterations predict response to brachytherapy treatment

Abstract

Abstract Background Discovery of ERG rearrangements and recurrent associated molecular alterations, such as PTEN deletions, has helped understand prostate carcinogenesis. However, prostate cancer (PCa) molecular stratification has not been well studied in response to different treatment modalities. The objective of this study was to evaluate the association of ERG rearrangements and PTEN deletions with oncologic outcomes in PCa patients treated with brachytherapy. Material and methods Ninety-two men underwent I-125 brachytherapy with a 145Gy delivered dose between 2000 and 2008. Pre-treatment prostate biopsies were analyzed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) for ERG rearrangement and overexpression, PTEN deletion and expression loss. Univariable and multivariable Cox-regression analyses evaluated association of ERG and PTEN status with biochemical recurrence (BCR). Results Within a median follow-up of 73 months, 11% of patients experienced BCR. Of 80 samples with both IHC and FISH performed for ERG, 46 (57.8%) demonstrated rearrangement by FISH and 45 (56.3%) by IHC. Of 77 samples with both IHC and FISH for PTEN, 14 (18.2%) had PTEN deletion by FISH and 22 (28.6%) by IHC. No significant associations were found between ERG, PTEN status and clinicopathologic features. Patients with concurrent ERG rearrangement and PTEN deletion demonstrated significantly worse relapse-free survival rates compared to those with ERG or PTEN wild-type (p<0.01). In multivariable Cox regression analysis adjusted for the effects of standard clinicopathologic features, combined ERG rearranged and PTEN deletion was independently associated with BCR (HR 2.6, p=0.02). Conclusions Concurrent ERG rearrangement and PTEN loss was independently associated with time to BCR in patients undergoing brachytherapy. Identifying patients in this molecular subclass may improve treatment personalization. Future studies are needed to validate PCa molecular subtyping for risk-stratification. Citation Format: Jacqueline Fontugne, Daniel Lee, Chiara Cantaloni, Christopher E. Barbieri, Caffo Orazio, Esther Hanspeter, Guido Mazzoleni, Paolo Dalla Palma, Mark A. Rubin, Giovanni Fellin, Juan Miguel Mosquera, Mattia Barbareschi, Francesca Demichelis. Recurrent prostate cancer genomic alterations predict response to brachytherapy treatment. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3952. doi:10.1158/1538-7445.AM2014-3952