PD08-08 RACIAL DISPARITIES IN THE FREQUENCY AND INTENSITY OF ACTIVE SURVEILLANCE FOR LOW RISK PROSTATE CANCER

Abstract

time is unknown. Using next generation sequencing (NGS), we sought to determine if a clonal focus can be tracked serially and if so, is there evidence that cancer progression at the molecular level can occur. METHODS: 31 men with Gleason 6 prostate cancer (CaP) were enrolled in an IRB-approved registry for AS. Subjects underwent MRI/ US fusion biopsy at study entry and re-sampling of the tracked biopsy site 1 year later. Immunohistochemistry (IHC) and targeted RNA/DNA NGS on routine formalin-fixed paraffin-embedded (FFPE) prostate biopsy tissues obtained at both time points were performed. ETS gene fusion status, a marker of CaP clonality and common oncogenic alterations associated with human cancer were assessed. RESULTS: In 96% of subjects (25 of 26 men with evaluable specimens), we found ERG expression concordance between targeted biopsy samples assessed over 1 year from the same site. Of the 11 men (35%) who progressed to higher grade cancer on targeted surveillance biopsy at 1 year, 100% (10/10; 1 not evaluable) displayed ERG concordance between initial and subsequent biopsy. Among these men, a driving mutation in IDH1 and SPOP was detected, in one patient each, in both the early (low grade) and late (higher grade) sample. In one case with progression to Gleason 8 disease, a TP53 mutation was detected in the late but not the early sample. In 2 out of 20 cases that did not progress, driving mutations in SPOP and BRCA2 were detected in the late sample only (Table 1). CONCLUSIONS: In this first of its kind study, employing sophisticated molecular techniques, we found that MRI/US targeted biopsy permits serial sampling of the same clonal focus of CaP over time. Furthermore, while molecular progression of low risk CaP appears to be uncommon over the course of 1 year, a proportion of high grade CaP appear to originate from low grade cancers and that de novo mutations in potential driver genes can occur. These findings provide a rationale for employing MRI/US fusion biopsy technique in monitoring men on AS for CaP and importantly imply that not all Gleason 6 CaP may be indolent.