TY - JOUR
T1 - Could circulating tumor cells and ARV7 detection improve clinical decisions in metastatic castration-resistant prostate cancer? The istituto nazionale dei tumori (INT) experience
AU - Sepe, Pierangela
AU - Verzoni, Elena
AU - Miodini, Patrizia
AU - Claps, Melanie
AU - Ratta, Raffaele
AU - Martinetti, Antonia
AU - Mennitto, Roberta
AU - Sottotetti, Elisa
AU - Procopio, Giuseppe
AU - Cappelletti, Vera
AU - Daidone, Maria Grazia
PY - 2019/7
Y1 - 2019/7
N2 - 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.
AB - 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.
KW - Abiraterone
KW - Androgen receptor splicing variants
KW - Castration-resistant prostate cancer
KW - Circulating tumor cells
KW - Enzalutamide
KW - Liquid biopsy
KW - Precision medicine
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U2 - 10.3390/cancers11070980
DO - 10.3390/cancers11070980
M3 - Article
AN - SCOPUS:85071368842
VL - 11
JO - Cancers
JF - Cancers
SN - 2072-6694
IS - 7
M1 - 980
ER -