PTEN Loss but Not ERG Expression in Diagnostic Biopsies Is Associated with Increased Risk of Progression and Adverse Surgical Findings in Men with Prostate Cancer on Active Surveillance

Background: Active surveillance (AS) is an option for men with low-risk prostate cancer (PCa). PTEN and ERG have been considered as potential biomarkers of PCa progression and survival.

Objective: To study the role of ERG and PTEN status in the Prostate Cancer Research International: Active Surveillance (PRIAS) trial diagnostic biopsies (DBxs) in predicting surveillance discontinuation and adverse surgical findings in subsequent radical prostatectomy (RP).

Design, setting, and participants: A total of 231 patients were recruited to the PRIAS between 2007 and 2013 in Helsinki. DBx tissue for immunohistochemistry (IHC) was available from 190 patients. Tissue microarrays (TMAs) were constructed from 57 specimens of subsequent RPs. DBxs containing grade group (GG) 1 PCa and RP TMA sections were stained with ERG and PTEN antibodies, and scored as either negative or positive.

Outcome measurements and statistical analyses: Outcomes were followed up by biopsy GG upgrade (GG ≥ 2) and protocol-based treatment change, as well as adverse findings in RP (GG ≥ 3 or pathological stage≥3). Clinical variables and biomarker status in DBx were correlated in Cox regression analysis and cumulative survival in Kaplan-Meier analysis, and finally, Gray's competing risk analysis was performed and nonprotocol-based discontinuation was considered as a competing event.

Results and limitations: In both uni- and multivariate Cox regression analyses, only the number of positive cores in the DBx, the number of rebiopsy sessions, and PTEN status at diagnosis were significantly associated with rebiopsy GG upgrade, treatment change, and adverse histopathology in RP. In Kaplan-Meier analysis, PTEN loss was associated with a shorter time to GG upgrade and treatment change. Patients with PTEN loss had a higher probability for protocol-based discontinuation but not for competing risk factors compared with patients with intact PTEN. Biopsy ERG status was concordant with RP TMA ERG status, while PTEN was not. Limitations include a retrospective analysis of prospective cohort data.

Conclusions: PTEN status at diagnosis is a potential biomarker for identifying patients with PCa on AS with a high risk for progression or adverse findings on subsequent RP.

Patient summary: A simple diagnostic biopsy-based analysis of PTEN status may help identify patients with high risk for prostate cancer progression.