Assessment of the variability of and effect of hormone therapy on circulating tumor cell numbers and androgen receptor expression in patients with prostate cancer.

Abstract

e15141 Background: In prostate cancer (PC) CTC number and character may offer a means of assessing disease load and target engagement. However, capture platforms differ, presenting challenges to enumeration and molecular characterisation. We report the findings of a pilot study assessing the intra- and inter-patient variability of 2 different platforms, and the feasibility of measuring CTC-androgen receptor (AR) expression by immunohistochemistry (IHC) in a single platform. Methods: Following ethical approval, 4 PC cohorts (n = 12, 12, 10, and 6 respectively) were recruited; #1 localised, no hormonal therapy; #2 and #3: castrate-resistant, receiving LHRHa or LHRHa and bicalutamide, respectively; #4: newly diagnosed locally advanced, no hormonal therapy. Blood (2 x 10 mL, 2 visits #1-3; 2 x 10 mL,1 visit #4) was taken and CTCs isolated using either the Cell Search CTC Test (Veridex) or Isolation by Size of Epithelial Cells Technique (ISET) for enumeration, and ISET for AR expression (H-score [(% 1*1+) + (% 2*2+) + (% 3*3+)]). Results: There was no correlation between Veridex and ISET for detection of CTCs (Veridex enumeration:14%, 63%, 53% and 0% of samples in #1 - 4, respectively, vs ISET enumeration: 100% of samples across all cohorts) with the latter platform detecting a significantly higher number of CTCs/4mls from patients in cohort #4 vs #1 (GLS Means 119 vs 46, p=0.0135). For both platforms there was no evidence of a systematic change in the counts at two separate visits 2 weeks apart. AR was detectable in approximately 25-35% CTCs from all cohorts and there were no significant differences in the H-score between the cohorts, although the number of AR-positive cells/4mls was significantly higher in #4 vs #1, and #2 (GLS Means 25 vs 14, 15, p= 0.0197, 0.0398, respectively). Conclusions: Populations of CTCs detected by Veridex and ISET appear stable over short durations (2 weeks) and AR was detected in a proportion of CTCs by ISET using IHC. Further work is required to find alternative methodologies with greater specificity.