PTEN Loss in Gleason Score 3+4=7 Prostate Biopsies is Associated with Nonorgan Confined Disease at Radical Prostatectomy

Purpose: Men with intermediate risk prostate cancer have widely variable outcomes. Some suggest that active surveillance or less invasive therapies (brachytherapy or focal therapy) may be appropriate for some men with Gleason score 3 + 4 = 7 disease. Molecular markers may help further distinguish prostate cancers with aggressive behavior. We tested whether loss of the PTEN (phosphatase and tensin homolog) tumor suppressor in 3 + 4 = 7 tumor biopsies is associated with adverse pathology at prostatectomy. Materials and Methods: We queried prostate needle biopsies from 2000 to 2014 with a maximum Gleason score of 3 + 4 = 7 followed by prostatectomy. A total of 260 cases had PTEN status evaluable by clinical grade immunohistochemistry. Biopsy PTEN status was correlated with preoperative and postoperative clinicopathological parameters. Results: PTEN loss was detected in 27% of 3 + 4 = 7 biopsies. Loss of PTEN was less common in tumors of African American men compared to European American men (9% vs 31%, p = 0.002). At prostatectomy, tumors with PTEN loss were more likely to show nonorgan confined disease compared to those with PTEN intact (52% vs 27%, p < 0.001). In logistic regression models including age, race, prostate specific antigen, clinical stage and biopsy tumor involvement, PTEN loss at biopsy remained significantly associated with an increased risk of nonorgan confined disease (HR 2.46, 95% CI 1.34-4.49, p = 0.004). On ROC analysis, the AUC for models including prostate specific antigen and clinical stage was increased from 0.61 to 0.67 upon inclusion of PTEN status. Conclusions: PTEN loss in a Gleason score 3 + 4 = 7 biopsy is independently associated with an increased risk of nonorgan confined disease at prostatectomy. It adds to the preoperative parameters commonly used to predict pathological stage.