EAU 2017: PTEN status in diagnostic biopsies predicts active surveillance rebiopsy Gleason upgrade, treatment change and adverse surgical histopathological findings

London, England (UroToday.com) The authors of this study attempt to identify a potential biomarker for clinical progression and survival in patients on active surveillance (AS) for low-risk, low-volume prostate cancer. Prior literature has demonstrated that protein expression of PTEN and ERG have been considered as potential biomarkers of PC progression and survival. ERG status has shown potential as a predictive biomarker in AS patients and PTEN status in diagnostic biopsies (DBx) has been shown to predict locally advanced disease in radical prostatectomy (RP) in patients with Gleason score 3+4. In this study, the authors compared both ERG and PTEN status in DBx of AS patients with rebiopsy Gleason upgrade, treatment change and adverse surgical findings.

The authors had access to 203 of the 231 patients enrolled in the PRIAS trial (launched 2007). Of these patients, 57 patients (24.7%) underwent RP and the RP pathology was analyzed in conjunction to biopsy tissue. DBx containing PC and the RP sections were stained with ERG antibody (clone EPR 3864, Abcam) and a PTEN antibody (clone D4.3 XP, Cell Signaling Technology). ERG and PTEN were then scored as either negative or positive. Biomarker status was analyzed in DBx with comparison to rebiopsy Gleason upgrade, treatment change and adverse findings in surgical specimens. In addition, concordance of biomarker status in DBx and RP specimen was evaluated.

Demographics of the groups are listed below:

chart 15

In univariate and multivariate cox regression analysis, only the number of positive cores in the diagnostic biopsy, the number re-biopsy sessions and PTEN status at diagnosis were significantly associated with re-biopsy Gleason upgrade, treatment change and adverse histopathological findings in RP specimens (Table 3).

chart 15b

Concordance of ERG and PTEN between dBx and RP specimen are highlighted in Table 2.

chart 15c

In Kaplan Meier analysis, PTEN loss was significantly associated with a shorter time to
Gleason upgrade or treatment change (P = 0.006). In Gray’s competing risk analysis, PTEN status was associated with Gleason upgrade AS discontinuation (P = 0.029).

Ultimately, it would seem that while ERG status correlated the best between dBx and RP specimen, it was PTEN loss that was more clinically relevant and predictive of progression and treatment change. However, the discordance between dBx and RP is a little disconcerting and not easily explained. Further work is needed in this area to determine if PTEN is truly a useful biomarker.

Speaker(s): Andrew Erickson

Co-Authors: Lokman U., Vasarainen H., Mirtti T., Rannikko A.

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the #EAU17 - March 24-28, 2017- London, England