Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer

Samanta Salvi, Valentina Casadio, Vincenza Conteduca, Cristian Lolli, Giorgia Gurioli, Filippo Martignano, Giuseppe Schepisi, Sara Testoni, Emanuela Scarpi, Dino Amadori, Daniele Calistri, Gerhardt Attard, Ugo de Giorgi

Research output: Contribution to journalArticle

Abstract

In the present study, we aimed to evaluate the association of circulating AR copy number (CN) and outcome in a cohort of patients with advanced castrationresistant prostate cancer (CRPC) treated with enzalutamide after docetaxel. Fiftynine CRPC patients were evaluated. AR CN was analyzed with real-time and digital PCR in the serum collected at starting of treatment. Progressive disease was defined on the basis of Prostate Cancer Working Group 2 criteria. AR CN gain was found in 21 of 59 (36%) patients. Median baseline PSA, alkaline phosphatase and lactate dehydrogenase levels were higher in the AR CN gained group (p = 0.007, p = 0.003, p = 0.0009, respectively). Median PFS of patients with AR CN gain was 2.4 (95%CI: 1.9-3.2) vs. 4.0 months (95%CI: 3.0-6.5) of those with no gain (p = 0.0004). Median OS of patients with AR CN gain was 6.1 (95%CI: 3.4-8.6) vs. 14.1 months (95%CI: 8.2-20.5) of those with no gain (p = 0.0003). At multivariate analysis, PSA decline ≥ 50% and AR CN showed a significant association with PFS (p = 0.008 and p = 0.002, respectively) and OS (p = 0.009 and p = 0.001, respectively). These findings indicate that the detection of circulating AR CN gain is a promising non-invasive biomarker for outcome prediction to enzalutamide treatment in CRPC patients.

Original languageEnglish
Pages (from-to)37839-37845
Number of pages7
JournalOncotarget
Volume7
Issue number25
DOIs
Publication statusPublished - 2016

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docetaxel
Castration
Prostatic Neoplasms
L-Lactate Dehydrogenase
Alkaline Phosphatase
MDV 3100
Real-Time Polymerase Chain Reaction
Multivariate Analysis
Biomarkers

Keywords

  • Androgen receptor
  • Circulating cell free DNA
  • Copy number variation
  • Enzalutamide
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology

Cite this

Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. / Salvi, Samanta; Casadio, Valentina; Conteduca, Vincenza; Lolli, Cristian; Gurioli, Giorgia; Martignano, Filippo; Schepisi, Giuseppe; Testoni, Sara; Scarpi, Emanuela; Amadori, Dino; Calistri, Daniele; Attard, Gerhardt; de Giorgi, Ugo.

In: Oncotarget, Vol. 7, No. 25, 2016, p. 37839-37845.

Research output: Contribution to journalArticle

Salvi, Samanta ; Casadio, Valentina ; Conteduca, Vincenza ; Lolli, Cristian ; Gurioli, Giorgia ; Martignano, Filippo ; Schepisi, Giuseppe ; Testoni, Sara ; Scarpi, Emanuela ; Amadori, Dino ; Calistri, Daniele ; Attard, Gerhardt ; de Giorgi, Ugo. / Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. In: Oncotarget. 2016 ; Vol. 7, No. 25. pp. 37839-37845.
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abstract = "In the present study, we aimed to evaluate the association of circulating AR copy number (CN) and outcome in a cohort of patients with advanced castrationresistant prostate cancer (CRPC) treated with enzalutamide after docetaxel. Fiftynine CRPC patients were evaluated. AR CN was analyzed with real-time and digital PCR in the serum collected at starting of treatment. Progressive disease was defined on the basis of Prostate Cancer Working Group 2 criteria. AR CN gain was found in 21 of 59 (36{\%}) patients. Median baseline PSA, alkaline phosphatase and lactate dehydrogenase levels were higher in the AR CN gained group (p = 0.007, p = 0.003, p = 0.0009, respectively). Median PFS of patients with AR CN gain was 2.4 (95{\%}CI: 1.9-3.2) vs. 4.0 months (95{\%}CI: 3.0-6.5) of those with no gain (p = 0.0004). Median OS of patients with AR CN gain was 6.1 (95{\%}CI: 3.4-8.6) vs. 14.1 months (95{\%}CI: 8.2-20.5) of those with no gain (p = 0.0003). At multivariate analysis, PSA decline ≥ 50{\%} and AR CN showed a significant association with PFS (p = 0.008 and p = 0.002, respectively) and OS (p = 0.009 and p = 0.001, respectively). These findings indicate that the detection of circulating AR CN gain is a promising non-invasive biomarker for outcome prediction to enzalutamide treatment in CRPC patients.",
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AU - Salvi, Samanta

AU - Casadio, Valentina

AU - Conteduca, Vincenza

AU - Lolli, Cristian

AU - Gurioli, Giorgia

AU - Martignano, Filippo

AU - Schepisi, Giuseppe

AU - Testoni, Sara

AU - Scarpi, Emanuela

AU - Amadori, Dino

AU - Calistri, Daniele

AU - Attard, Gerhardt

AU - de Giorgi, Ugo

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AB - In the present study, we aimed to evaluate the association of circulating AR copy number (CN) and outcome in a cohort of patients with advanced castrationresistant prostate cancer (CRPC) treated with enzalutamide after docetaxel. Fiftynine CRPC patients were evaluated. AR CN was analyzed with real-time and digital PCR in the serum collected at starting of treatment. Progressive disease was defined on the basis of Prostate Cancer Working Group 2 criteria. AR CN gain was found in 21 of 59 (36%) patients. Median baseline PSA, alkaline phosphatase and lactate dehydrogenase levels were higher in the AR CN gained group (p = 0.007, p = 0.003, p = 0.0009, respectively). Median PFS of patients with AR CN gain was 2.4 (95%CI: 1.9-3.2) vs. 4.0 months (95%CI: 3.0-6.5) of those with no gain (p = 0.0004). Median OS of patients with AR CN gain was 6.1 (95%CI: 3.4-8.6) vs. 14.1 months (95%CI: 8.2-20.5) of those with no gain (p = 0.0003). At multivariate analysis, PSA decline ≥ 50% and AR CN showed a significant association with PFS (p = 0.008 and p = 0.002, respectively) and OS (p = 0.009 and p = 0.001, respectively). These findings indicate that the detection of circulating AR CN gain is a promising non-invasive biomarker for outcome prediction to enzalutamide treatment in CRPC patients.

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