Prognostic Utility of Biopsy-Based PTEN and ERG Status on Biochemical Progression and Overall Survival after SBRT for Localized Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> PTEN deletions and ERG rearrangements are two of the most common genetic abnormalities associated with prostate cancer. Prior studies revealed that changes in wild-type PTEN and ERG portend worse clinical outcomes. While early studies were performed on whole-gland samples after radical prostatectomy, subsequent biopsy-based analyses have led to their inclusion in several genomic assays and prostate cancer outcome scores. However, evaluations of therapeutic response to radiotherapy are quite heterogenous. Our objective is to evaluate the impact of biopsy-determined <i>PTEN</i> losses and <i>TMPRSS2-ERG</i> fusion on biochemical disease-free survival (bDFS) in patients who receive SBRT for localized prostate cancer. <h3>Materials/Methods</h3> Patients included in this analysis underwent SBRT for localized prostate cancer and are followed on an institutional prospective quality of life and survival study. For each patient, the single biopsy core with the highest volume of cancer was evaluated for PTEN and ERG abnormalities. Differences in baseline patient and disease characteristics between groups were analyzed using ANOVA for age and χ<b>²</b> for categorical groupings. bDFS and OS were calculated using the Kaplan Meier (KM) method with Log-Rank test comparison between groups. Predictors of bDFS and OS were evaluated using Cox proportional hazard method. For all analyses, <i>p</i> <0.05 was considered statistically significant. <h3>Results</h3> Ninety-three patients were included in the analysis with a median follow up of 72 months (IQR 52 - 85 months). The 5-year bDFS for all patients was 85.2% with a median bDFS of 98 months. The 5-year OS for all patients was 91.8% with a median OS of 123 months. Differences between ERG and PTEN status groups by age, race, T-stage, NCCN risk group, PSA group, PSA density group, and Charlson Comorbidity Index were not statistically significant. Differences in grade group were statistically significant (<i>p</i> = 0.0329). The estimated 5-year bDFS was 100%, 76.6%, 72.9%, and 63.8% for the ERG+/PTEN, ERG-/PTEN+, ERG+/PTEN-, and ERG-/PTEN- groups respectively (<i>p</i> =0.0107). Multivariate analysis (MVA) confirmed an increased likelihood of 5-year biochemical progression with higher NCCN risk group (<i>p</i> <0.0001) and increasing ERG/PTEN mutational burden (<i>p</i><0.0001). <h3>Conclusion</h3> <i>ERG Fusion with PTEN</i> loss is associated with an increased risk of biochemical progression. However, <i>ERG</i> status alone is not predictive of bPFS. Biopsy-based PTEN and ERG assays demonstrate utility in predicting 5-year oncologic outcomes in patients who receive prostate SBRT.