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Cancers (Basel). 2019 Sep 13;11(9). doi: 10.3390/cancers11091365.

Role of Circulating Tumor Cells (CTC), Androgen Receptor Full Length (AR-FL) and Androgen Receptor Splice Variant 7 (AR-V7) in a Prospective Cohort of Castration-Resistant Metastatic Prostate Cancer Patients.

Cancers

Carlo Cattrini, Alessandra Rubagotti, Linda Zinoli, Luigi Cerbone, Elisa Zanardi, Matteo Capaia, Paola Barboro, Francesco Boccardo

Affiliations

  1. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  2. Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132 Genoa, Italy. [email protected].
  3. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  4. Department of Health Sciences (DISSAL), School of Medicine, University of Genoa, 16132 Genoa, Italy. [email protected].
  5. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  6. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  7. Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132 Genoa, Italy. [email protected].
  8. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  9. Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132 Genoa, Italy. [email protected].
  10. Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132 Genoa, Italy. [email protected].
  11. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  12. Academic Unit of Medical Oncology, IRCCS San Martino Polyclinic Hospital, 16132 Genoa, Italy. [email protected].
  13. Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132 Genoa, Italy. [email protected].

PMID: 31540293 PMCID: PMC6770005 DOI: 10.3390/cancers11091365

Abstract

BACKGROUND: Circulating tumor cells (CTC), androgen receptor full-length (AR-FL), and androgen receptor splice variant 7 (AR-V7) are prognostic in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). AR-V7 seems to predict resistance to androgen-receptor signaling inhibitors (ARSi).

METHODS: We assessed the association of CTC, AR-FL, and AR-V7 with prostate-specific antigen (PSA) response and overall survival (OS). We used a modified AdnaTest CTC-based AR-FL and AR-V7 mRNA assay. Chi-square test, Fisher Exact test, Kaplan-Meier method, log-rank test, Cox proportional hazards models were used as appropriate.

RESULTS: We enrolled 39 mCRPC pts, of those 24 started a first-line treatment for mCRPC (1L subgroup) and 15 had received at least two lines for mCRPC (>2L subgroup). CTC, AR-FL, and AR-V7 were enriched in >2L compared to 1L subgroup. Detection of these biomarkers was associated with a lower percentage of biochemical responses. Only 1/7 AR-V7+ pts had a PSA response and received cabazitaxel. Median OS was 4.7 months (95% CI 0.6-8.9) in AR-V7+ pts and not reached in AR-V7- pts. AR-V7 was the only variable with prognostic significance in the Cox model.

CONCLUSION: AR-V7, CTC, and AR-FL are associated with advanced mCRPC and AR-V7+ predicts for shorter OS.

Keywords: AR-FL; AR-V7; castration-resistant prostate cancer; circulating tumor cells; prognostic biomarkers

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