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Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience

Enzalutamide and abiraterone have been shown to improve progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. Moreover, some patients may not benefit from the inhibition of androgen receptor (AR) activity or, alternatively, may...

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Autores principales: Sepe, Pierangela, Verzoni, Elena, Miodini, Patrizia, Claps, Melanie, Ratta, Raffaele, Martinetti, Antonia, Mennitto, Roberta, Sottotetti, Elisa, Procopio, Giuseppe, Cappelletti, Vera, Daidone, Maria Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678845/
https://www.ncbi.nlm.nih.gov/pubmed/31337040
http://dx.doi.org/10.3390/cancers11070980
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author Sepe, Pierangela
Verzoni, Elena
Miodini, Patrizia
Claps, Melanie
Ratta, Raffaele
Martinetti, Antonia
Mennitto, Roberta
Sottotetti, Elisa
Procopio, Giuseppe
Cappelletti, Vera
Daidone, Maria Grazia
author_facet Sepe, Pierangela
Verzoni, Elena
Miodini, Patrizia
Claps, Melanie
Ratta, Raffaele
Martinetti, Antonia
Mennitto, Roberta
Sottotetti, Elisa
Procopio, Giuseppe
Cappelletti, Vera
Daidone, Maria Grazia
author_sort Sepe, Pierangela
collection PubMed
description Enzalutamide and abiraterone have been shown to improve progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. Moreover, some patients may not benefit from the inhibition of androgen receptor (AR) activity or, alternatively, may develop secondary resistance. Detection in patients’ circulating tumor cells (CTCs) of ARV7, a splicing variant of AR lacking the ligand-binding domain, showed a link with treatment failure. Independent confirmation of the predictive role of CTC status combined with ARV7 detection is, therefore, a priority for extending personalized biomarker-driven treatments to all patients. In this prospective observational study, CTC status and the expression of AR and ARV7 were measured in 37 mCRPC patients, before starting treatment with enzalutamide or abiraterone, by employing commercially available kits. CTC status was positive in 21/37 patients: 46% and 24% of CTC-positive patients were defined as AR- and ARV7-positive, respectively. Kaplan–Meier estimates showed that positivity for each variable was significantly associated with poorer radiological PFS, PSA-PFS, and OS. All considered treatment outcomes worsened when going from CTC-negative to CTC-positive/ARV7-negative to CTC-positive/ARV7-positive patients, both in the global case series and in patients stratified into three groups based on basal PSA levels. Presently, technical approaches appear to be mature for introducing CTC/ARV7 tests in clinical practice.
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spelling pubmed-66788452019-08-19 Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience Sepe, Pierangela Verzoni, Elena Miodini, Patrizia Claps, Melanie Ratta, Raffaele Martinetti, Antonia Mennitto, Roberta Sottotetti, Elisa Procopio, Giuseppe Cappelletti, Vera Daidone, Maria Grazia Cancers (Basel) Article Enzalutamide and abiraterone have been shown to improve progression-free survival (PFS) and overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients. Moreover, some patients may not benefit from the inhibition of androgen receptor (AR) activity or, alternatively, may develop secondary resistance. Detection in patients’ circulating tumor cells (CTCs) of ARV7, a splicing variant of AR lacking the ligand-binding domain, showed a link with treatment failure. Independent confirmation of the predictive role of CTC status combined with ARV7 detection is, therefore, a priority for extending personalized biomarker-driven treatments to all patients. In this prospective observational study, CTC status and the expression of AR and ARV7 were measured in 37 mCRPC patients, before starting treatment with enzalutamide or abiraterone, by employing commercially available kits. CTC status was positive in 21/37 patients: 46% and 24% of CTC-positive patients were defined as AR- and ARV7-positive, respectively. Kaplan–Meier estimates showed that positivity for each variable was significantly associated with poorer radiological PFS, PSA-PFS, and OS. All considered treatment outcomes worsened when going from CTC-negative to CTC-positive/ARV7-negative to CTC-positive/ARV7-positive patients, both in the global case series and in patients stratified into three groups based on basal PSA levels. Presently, technical approaches appear to be mature for introducing CTC/ARV7 tests in clinical practice. MDPI 2019-07-13 /pmc/articles/PMC6678845/ /pubmed/31337040 http://dx.doi.org/10.3390/cancers11070980 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sepe, Pierangela
Verzoni, Elena
Miodini, Patrizia
Claps, Melanie
Ratta, Raffaele
Martinetti, Antonia
Mennitto, Roberta
Sottotetti, Elisa
Procopio, Giuseppe
Cappelletti, Vera
Daidone, Maria Grazia
Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
title Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
title_full Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
title_fullStr Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
title_full_unstemmed Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
title_short Could Circulating Tumor Cells and ARV7 Detection Improve Clinical Decisions in Metastatic Castration-Resistant Prostate Cancer? The Istituto Nazionale dei Tumori (INT) Experience
title_sort could circulating tumor cells and arv7 detection improve clinical decisions in metastatic castration-resistant prostate cancer? the istituto nazionale dei tumori (int) experience
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678845/
https://www.ncbi.nlm.nih.gov/pubmed/31337040
http://dx.doi.org/10.3390/cancers11070980
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