Pilot study of CTC enumeration and AR-V7 detection using a microporous chip filtration system in metastatic prostate cancer.

Abstract

e17054 Background: Circulating tumor cells (CTC) are one of key components of liquid biopsy which provide phenotype and molecular information of prostate cancer (PCa). The androgen receptor splice variant 7 (AR-V7) has been implicated as a marker of resistance to androgen receptor pathway inhibitors (ARPI) in PCa. An automated high density microporous chip filtration system (Smart Biopsy Cytogen, Seoul, Korea) utilizes size-based physical separation, taking advantage of the relatively large size and rigidity of CTCs compared to leukocytes and erythrocytes. This study was conducted to evaluate CTC counts and AR-V7 detection from the blood of metastatic prostate cancer (mPCa) patients using Smart Biopsy. Methods: 20ml of Peripheral blood samples from 12 patients with mPCa and 5 healthy controls were collected. CTCs were isolated from 5ml of blood using Smart Biopsy. 15ml of blood was used for AR-V7 detection by droplet digital PCR (ddPCR). The patients were divided into an ARPI sensitive group and an ARPI refractory group to compare age, Gleason grade, time since metastasis, PSA, and CTC and ddPCR counts and follow-up PSA 6months after CTC analysis. Results: Median age of patient group and control group were 73.0 (range 58.0–85.0) and 43.5 (range 35.0–56.0; p < 0.001), respectively. Median follow up period after ARPI treatment was 25 months (range 1-144). The median CTC count was significantly higher in mPCa patients compared to controls (18 vs 1; p = 0.003). Median time since metastasis was significantly longer in the refractory group (32 months vs 6 months, p = 0.022) (Table). Although baseline PSA levels showed no significant difference, follow-up PSA was markedly higher in the refractory group (156 ng/mL vs 0.64 ng/mL, p = 0.017). CTC counts and ddPCR levels showed no significant intergroup differences, but patients with CTC ≥ 10 were more frequent in the refractory cohort (100% vs 33.3%; p = 0.046). Conclusions: This pilot study demonstrates the feasibility of using a microporous chip–based system for the isolation and molecular analysis of CTCs in patients with metastatic prostate cancer. The system effectively distinguished mPCa patients from healthy controls and showed significant correlation with ARPI resistance. These findings suggest that Smart Biopsymay serve as a promising, non-invasive tool to guide ARPI treatment strategies in mPCa. Comparison of molecular characteristics of patients with mPCa according to ARPI response status. Variable ARPI effective (n=3) ARPI refractory (n=9) p-value Age (years) 73.0 (63.0–85.0) 78.0 (58.0–81.0) 0.926 Gleason grade 0.250 3 1 (33.3%) 0 4 2 (66.6%) 4 (44.4) 5 0 5 (55.6) Time since metastasis (mo) 6 (3 – 6) 32 (12 – 144) 0.022 PSA (ng/mL) 742.0 (451.4–1460.0) 161.0 (0.7–900.0) 0.064 CTC/5mL 9 (8 –90) 40 (10–926) 0.2664 CTC≧10 (n) 1 (33.3%) 9 (100%) 0.0455 ddPCR 1.5 (0 – 6) 2 (0 - 24) 0.6404 F/U PSA (ng/mL) 0.64 (0.01 – 1.18) 156 (2.97 – 653.0) 0.017