Assessment of Total, PTEN–, and AR-V7+ Circulating Tumor Cell Count by Flow Cytometry in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide
التفاصيل البيبلوغرافية
العنوان:
Assessment of Total, PTEN–, and AR-V7+ Circulating Tumor Cell Count by Flow Cytometry in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide
Di Lorenzo, G., Zappavigna, S., Crocetto, F., Giuliano, M., Ribera, D., Morra, R., Scafuri, L., Verde, A., Bruzzese, D., Iaccarino, S., Costabile, F., Onofrio, L., Viggiani, M., Palmieri, A., De Placido, P., Marretta, A. L., Pietroluongo, E., Luce, A., Abate, M., Navaeiseddighi, Z., Caputo, V. F., Celentano, G., Longo, N., Ferro, M., Morelli, F., Facchini, G., Caraglia, M., De Placido, S., Buonerba, C., Lorenzo, G. D.
Introduction. 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, whereas 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 mCRPC. Patients and methods. In this translational study, we employed flow cytometry to assess total, PTEN–, and AR-V7+ CTC count per 7.5 mL of whole blood in a prospective cohort of patients with mCRPC receiving enzalutamide. Results. CTCs were assessed in a total of 45 men with mCRPC at baseline and at 12 weeks. Overall, CTC, PTEN– CTC, and AR-V7+ CTC detection rate was high, at baseline, with 84.4%, 71.1%, and 51.1% of samples showing at least 1 cell/7.5-mL blood, respectively, and after 3 months, with 93.3%, 64.4%, and 77.7% of samples showing at least 1 cell/7.5-mL blood, respectively. Median radiographic progression-free survival (rPFS) and OS were 6 (95% confidence interval [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), whereas 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 versus < 5 total CTC count was associated with worse rPFS (hazard ratio [HR], 2.35; 95% CI, 1.14-4.84; P=.021) and OS (HR, 3.08; 95% CI, 1.45-6.54; P =.003), whereas ≥ 2 versus < 2 PTEN– CTC count was associated with worse rPFS (HR, 3.96; 95% CI, 1.8-8.72; P=.001) and OS (HR, 2.36; 95% CI, 1.12-5; P=.025). Finally, ≥ 1 versus < 1 AR-V7+ CTC count was also associated with worse rPFS (HR, 5.05; 95% CI, 2.4-10.64; P
