Recurrent prostate cancer genomic alterations predict response to brachytherapy treatment.

Abstract

BACKGROUND:

This study aimed to evaluate the association of recurrent molecular alterations in prostate cancer, such as ERG rearrangements and phosphatase and tensin homolog gene (PTEN) deletions, with oncologic outcomes in patients with prostate cancer treated with brachytherapy.

METHODS:

Ninety-two men underwent I-125 brachytherapy with a 145 Gy delivered dose between 2000 and 2008. Pretreatment prostate biopsies were analyzed by immunohistochemistry (IHC) and 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 with 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. Future studies are needed to validate prostate cancer molecular subtyping for risk stratification.

IMPACT:

Identifying patients in the ERG-rearranged/PTEN-deleted molecular subclass may improve treatment personalization.

• Authors: Jacqueline Fontugne, Daniel Lee, Chiara Cantaloni, Christopher E Barbieri, Orazio Caffo, Esther Hanspeter, Guido Mazzoleni, Paolo Dalla Palma, Mark A Rubin, Giovanni Fellin, Juan Miguel Mosquera, Mattia Barbareschi, Francesca Demichelis
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 23 Issue 4 Pg. 594-600 (Apr 2014) ISSN: 1538-7755 [Electronic] United States
• PMID: 24515272 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Aged
• Brachytherapy (methods)
• Genomics (methods)
• Humans
• Male
• Neoplasm Recurrence, Local (genetics, pathology)
• Prostatic Neoplasms (genetics, pathology, radiotherapy)