Assessment of total, PTEN— and ARV-7+ circulating tumor cells count by flow cytometry in patients with metastatic castration-resistant prostate cancer receiving enzalutamide

Abstract Metastatic castration resistant prostate cancer (mCRPC) is a deadly disease. Enzalutamide is an oral second-generation anti-androgen that is active in mCRPC. Circulating tumor cells (CTC) count correlates with overall survival (OS) in mCRPC, while detection of the androgen-receptor splice variant 7 (AR-V7) in CTC predicts poor response to oral second-generation anti-androgens. Also, loss of PTEN (Phosphatase and tensin homolog) in CTC is a biomarker of poor prognosis in mCRCP. In this translational study, we employed flow cytometry to assess total, PTEN— and ARV-7+ CTC count per 7.5 mL of whole blood in a prospective cohort of mCRPC patients receiving enzalutamide. CTC were assessed in a total of 45 mCRPC men at baseline and at 12 weeks. Overall, CTC, PTEN- CTC and ARV-7+ CTC detection rate was high, both at baseline, with 84.4, 71.1 and 51,1% of samples showing at least 1 cell / 7.5 ml blood, respectively, and after three months, with 93.3, 64.4 and 77.7% of samples showing at least 1 cell / 7.5 blood respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% CI: 5.6–9) and 14.3 (95% CI: 12.8–20.3) months, respectively. Median (interquartile range) total CTC count at baseline was 5 (3; 8), while median (interquartile range) PTEN— CTC count was 2 (0; 4) and median (interquartile range) AR-V7+ CTC count was 1 (0; 3). At baseline, >=5 vs. =2 vs. = 1 vs. Micro-Abstract: In this study men with metastatic castration resistant prostate cancer, scheduled to start enzalutamide, were assessed for circulating tumor cells count and molecular characterization (total, PTEN— and ARV-7+ circulating tumor cells count) by the use of flow cytometry. We found that flow cytometry could be used to enumerate circulating tumor cells, but also to assess molecular biomarkers on their surface.