Prognostic and predictive role of CTCs and AR-V7+ CTCs expression in metastatic catrate resistant prostate cancer (mCRPC): A feasibility study.

Abstract

367 Background: Circulating tumor cells (CTC) counts ≥ 5/7.5 mL predict shorter survival in patients (pts) with mCRPC. Moreover, the presence of androgen receptor splice variant-7 mRNA (AR-V7) in CTCs is thought to play a relevant role in the development of primary or acquired resistance to enzalutamide (E) or abiraterone (A). We developed a new immunofluorescence-based assay for AR-V7+ CTCs and tested its association with PFS and OS. Methods: We performed a single-centre observational prospective trial enrolling pts with mCRPC candidate to receive E or A. CTC samples have been collected at baseline, after 1 month (mo) and every 3 mos thereafter until progression or at 12 mos without progression. CTCs have been enumerated with CellSearch System. We integrated the standard assay with a mAb able to recognize the AR-V7 protein. Slides from samples underwent automated immunofluorescent staining and AR-V7+ CTCs were enumerated. Results: Since Sep 2016, 31 pts have been enrolled (Table). We compared CTC counts between standard and the integrated assay and found no differences in the mean total CTC number ± (Wilcoxon Signed Rank test, p= 0.31). 16 out of 28 evaluable pts (57%) had ≥ 1 CTCs at baseline, 9 pts (32%) had ≥ 5 CTCs/7.5 ml, 4 pts (14.3%) were AR-V7+ before any exposure to A or E. After a median follow-up time of 8.1 mos, 6 pts have progressed and 4 died. No association has been found between CTCs ≥ 5/7.5 mL and survival. The presence of at least 1 AR-V7+ CTC at baseline did not correlate with PSA response, but had a weak association with shorter PFS (log-rank test, p = 0.055) and a significant impact (p = 0.02) on OS. Conclusions: We developed a new integrated assay for AR-V7+ CTCs, based on an automated platform that permits serial sampling with low inter- / intra-test variability. The clinical utility in anticipating the resistance to E or A is under study. [Table: see text]