Plasma androgen receptor and serum chromogranin A in advanced prostate cancer. Issue 1 (December 2018)

• Record Type: Journal Article
• Authors: Conteduca, Vincenza; Scarpi, Emanuela; Salvi, Samanta; Casadio, Valentina; Lolli, Cristian; Gurioli, Giorgia; Schepisi, Giuseppe; Wetterskog, Daniel; Farolfi, Alberto; Menna, Cecilia; De Lisi, Delia; Burgio, Salvatore; Beltran, Himisha; Attard, Gerhardt; De Giorgi, Ugo
• Is Part Of: Scientific reports. Volume 8:Issue 1(2018)
• Page Start: 1
• Page End: 8
• Publication Date: 2018-12
• Subjects: Natural history -- Research -- Periodicals; Biology -- Research -- Periodicals; Physical sciences -- Research -- Periodicals; Earth sciences -- Research -- Periodicals; Environmental sciences -- Research -- Periodicals; 502.85
• DOI: 10.1038/s41598-018-33774-4
• Languages: English
• ISSNs: 2045-2322

Abstract

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 circulatingAR 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, plasmaAR 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 noAR -aberrations. Multivariable analysis showedAR 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 inAR -normal patients. This association needs further evaluation in larger prospective cohorts.