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

Genitourinary Cancer
Session Type and Session Title: 
This abstract will not be presented at the 2012 ASCO Annual Meeting but has been published in conjunction with the meeting.
Abstract Number: 


J Clin Oncol 30, 2012 (suppl; abstr e15141)
Noel W Clarke, Sarah E Marley, Andrew M. Hughes, Anthony F Nash, Michael D Malone, Jim W Growcott, Darren R Hodgson, Robert Sloane, David J Moore, Tim H Ward, P. Anthony Elliott, Caroline Dive; Department of Urology, The Christie NHS Foundation Trust, Manchester, United Kingdom; AstraZeneca, Macclesfield, United Kingdom; AstraZeneca Pharmaceuticals, Macclesfield, United Kingdom; Paterson Institute for Cancer Research, The University of Manchester, Manchester, United Kingdom; Paterson Institute for Cancer Research, Manchester, United Kingdom; The Christie NHS Foundation Trust, Manchester, United Kingdom

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


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.