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Assessment of Total, PTEN-, and AR-V7+ Circulating Tumor Cell Count by Flow Cytometry in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Enzalutamide.

Authors
  • Di Lorenzo, Giuseppe1
  • Zappavigna, Silvia2
  • Crocetto, Felice3
  • Giuliano, Mario4
  • Ribera, Dario5
  • Morra, Rocco5
  • Scafuri, Luca5
  • Verde, Antonio5
  • Bruzzese, Dario6
  • Iaccarino, Simona5
  • Costabile, Ferdinando5
  • Onofrio, Livia5
  • Viggiani, Martina5
  • Palmieri, Alessandro3
  • De Placido, Pietro5
  • Marretta, Antonella Lucia5
  • Pietroluongo, Erica5
  • Luce, Amalia2
  • Abate, Marianna2
  • Navaeiseddighi, Zahrasadat2
  • And 9 more
  • 1 Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy; Department of Medicine and Health Sciences "Vincenzo Tiberio," University of Molise, Campobasso, Italy; Department of Oncology, Hospital "Andrea Tortora," ASL Salerno, Pagani, Italy; Department of Oncology and Hematology, AOU Federico II of Naples, Naples, Italy. , (Italy)
  • 2 Department of Precision Medicine, University of Campania "L. Vanvitelli," Naples, Italy. , (Italy)
  • 3 Department of Neurosciences, Human Reproduction and Odontostomatology, University of Naples Federico II, Naples, Italy. , (Italy)
  • 4 Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy; Regional Reference Center for Rare Tumors, Department of Oncology and Hematology, AOU Federico II of Naples, Naples, Italy. , (Italy)
  • 5 Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy. , (Italy)
  • 6 Department of Public Health, University of Naples "Federico II," Naples, Italy. , (Italy)
  • 7 Division of Urology, European Institute of Oncology-IRCCS, Milan, Italy. , (Italy)
  • 8 Medical Oncology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. , (Italy)
  • 9 Departmental Unit of Experimental Uro-Andrological Clinical Oncology, Department of Uro-Gynaecological Oncology, National Cancer Institute-IRCCS-G. Pascale Foundation, Naples, Italy. , (Italy)
  • 10 Department of Precision Medicine, University of Campania "L. Vanvitelli," Naples, Italy; Biogem Scarl, Institute of Genetic Research, Laboratory of Precision Medicine and Molecular Oncology, Ariano Irpino, Italy. , (Italy)
  • 11 Department of Clinical Medicine and Surgery, University Federico II of Naples, Naples, Italy; Regional Reference Center for Rare Tumors, Department of Oncology and Hematology, AOU Federico II of Naples, Naples, Italy. Electronic address: [email protected] , (Italy)
Type
Published Article
Journal
Clinical Genitourinary Cancer
Publisher
Elsevier
Publication Date
Oct 01, 2021
Volume
19
Issue
5
Identifiers
DOI: 10.1016/j.clgc.2021.03.021
PMID: 33958297
Source
Medline
Keywords
Language
English
License
Unknown

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, 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. 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. 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< .001) and OS (HR, 2.25; 95% CI, 1.1-4.58; P= .026). Despite multiple limitations, including the small sample size, our preliminary study suggests that assessment of CTC via flow cytometry may provide potentially useful prognostic and predictive information in advanced prostate cancer. Further studies are warranted. Micro-Abstract: In this study, men with metastatic castration-resistant prostate cancer, scheduled to start enzalutamide, were assessed for circulating tumor cell count and molecular characterization (total, PTEN-, and AR-V7+ circulating tumor cell 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. Copyright © 2021 Elsevier Inc. All rights reserved.

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