Abstract | INTRODUCTION: 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< .001) and OS (HR, 2.25; 95% CI, 1.1-4.58; P= .026). CONCLUSIONS: 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.
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Authors | Giuseppe Di Lorenzo, Silvia Zappavigna, Felice Crocetto, Mario Giuliano, Dario Ribera, Rocco Morra, Luca Scafuri, Antonio Verde, Dario Bruzzese, Simona Iaccarino, Ferdinando Costabile, Livia Onofrio, Martina Viggiani, Alessandro Palmieri, Pietro De Placido, Antonella Lucia Marretta, Erica Pietroluongo, Amalia Luce, Marianna Abate, Zahrasadat Navaeiseddighi, Vincenzo Francesco Caputo, Giuseppe Celentano, Nicola Longo, Matteo Ferro, Franco Morelli, Gaetano Facchini, Michele Caraglia, Sabino De Placido, Carlo Buonerba |
Journal | Clinical genitourinary cancer
(Clin Genitourin Cancer)
Vol. 19
Issue 5
Pg. e286-e298
(10 2021)
ISSN: 1938-0682 [Electronic] United States |
PMID | 33958297
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2021 Elsevier Inc. All rights reserved. |
Chemical References |
- Benzamides
- Biomarkers, Tumor
- Nitriles
- Protein Isoforms
- Receptors, Androgen
- Phenylthiohydantoin
- enzalutamide
- PTEN Phosphohydrolase
- PTEN protein, human
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Topics |
- Benzamides
- Biomarkers, Tumor
- Flow Cytometry
- Humans
- Male
- Neoplastic Cells, Circulating
- Nitriles
- PTEN Phosphohydrolase
(genetics)
- Phenylthiohydantoin
- Prospective Studies
- Prostatic Neoplasms, Castration-Resistant
(drug therapy)
- Protein Isoforms
- Receptors, Androgen
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