Plasma androgen receptor and serum chromogranin A in advanced prostate cancer

Vincenza Conteduca, Emanuela Scarpi, Samanta Salvi, Valentina Casadio, Cristian Lolli, Giorgia Gurioli, Giuseppe Schepisi, Daniel Wetterskog, Alberto Farolfi, Cecilia Menna, Delia De Lisi, Salvatore Luca Burgio, Himisha Beltran, Gerhardt Attard, Ugo De Giorgi

Research output: Contribution to journalArticlepeer-review

Abstract

Recently, mixed forms between adenocarcinoma and neuroendocrine prostate cancer (NEPC) have emerged that are characterized by persistent androgen receptor (AR)-signalling and elevated chromogranin A (CgA) levels. The main aim of this study was to analyze castration-resistant prostate cancer (CRPC) patients treated with abiraterone or enzalutamide, assessing progression-free/overall survival (PFS/OS) in association with circulating AR and CgA. AR aberrations were analyzed by droplet digital PCR in pre-treatment plasma samples collected from two biomarker protocols [197 patients from a retrospective study (REC 2192/2013) and 59 from a prospective trial (REC 6798/2015)]. We subdivided patients into three groups according to CgA by receiver-operating characteristic (ROC) curves. In the primary cohort, plasma AR gain and mutations (p.L702H/p.T878A) were detected in 78 (39.6%) and 16 (8.1%) patients, respectively. We observed a significantly worse PFS/OS in patients with higher-CgA than in patients with normal-CgA, especially those with no AR-aberrations. Multivariable analysis showed AR gain, higher-CgA and LDH levels as independent predictors of PFS [hazard ratio (HR) = 2.16, 95% confidence interval (95% CI) 1.50–3.12, p < 0.0001, HR = 1.73, 95% CI 1.06–2.84, p = 0.026, and HR = 2.13, 95% CI 1.45–3.13, p = 0.0001, respectively) and OS (HR = 1.72, 95% CI 1.15–2.57, p = 0.008, HR = 3.63, 95% CI 2.13–6.20, p < 0.0001, and HR = 2.31, 95% CI 1.54–3.48, p < 0.0001, respectively). These data were confirmed in the secondary cohort. Pre-treatment CgA detection could be useful to identify these mixed tumors and would seem to have a prognostic role, especially in AR-normal patients. This association needs further evaluation in larger prospective cohorts.

Original languageEnglish
Article number15442
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

ASJC Scopus subject areas

  • General

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