title: Influence of abiraterone acetate on circulating neuromediators in chemotherapy-naïve castration-resistant prostate cancer.
abstract: BACKGROUND
  Abiraterone Acetate (AA) represents a highly effective androgen-receptor (AR) axis targeted agent. Treatment with AA in castration-resistant prostate cancer (CRPC) may partly mediate neuroendocrine differentiation (NED) as an escape mechanism, which may have implications for the choice of sequential therapy in CRPC. We evaluated how treatment with AA influences circulating neuromediators chromogranin A (CGA), neuron-specific enolase (NSE), and pro-gastrin-releasing peptide (Pro-GRP) in chemotherapy-naïve CRPC patients.
  
  
  METHODS
  We conducted an analysis in chemotherapy-naïve CRPC patients with clinical or radiographic progression of disease. A total of 35 patients were included at five institutions between February 2013 and December 2014. Sixteen of them had received AA. Serum samples were obtained before a docetaxel-based chemotherapy and analyzed in a reference laboratory. Univariable and multivariable analyses were performed to test the influence of AA treatment, its duration of treatment, and other clinicopathological variables on circulating neuromediators.
  
  
  RESULTS
  CGA and NSE levels were above the upper limit of normal (ULN) in n = 20 (57.1%) and n = 13 (37.1%), respectively. Treatment with AA and duration of treatment were not associated with levels above the ULN (CGA and NSE) or higher levels (Pro-GRP) of neuromediators. CGA levels were associated with age (P = 0.092), lymph node metastasis (P = 0.014), duration of androgen deprivation therapy (ADT; P = 0.083), and intake of proton pump inhibitors (P = 0.069). Pro-GRP levels were significantly associated with PSA levels (P = 0.002). On multivariate analysis, CGA levels above the ULN were significantly correlated with ADT (P = 0.01) and intake of proton pump inhibitors (P = 0.03).
  
  
  CONCLUSIONS
  Circulating neuromediators in chemotherapy-naïve CRPC patients were elevated in a high percentage of patients. ADT was found to be a relevant NED driver in this cohort. Our results may imply that patients with CRPC after first-line treatment with AA in CRPC are not at a higher risk for developing NED. The major limitation of the study represents the one-time analysis of neuromediators. Larger studies with serial blood measurements or biopsy analysis before and after treatment are needed to confirm our results.
authors.affiliation: Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Jost
authors.initials: J
authors.lastname: von Hardenberg
authors.affiliation: Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Schwartz
authors.affiliation: Outpatient Urology Practice, Herzberg am Harz, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Werner
authors.affiliation: Outpatient Oncology Practice Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fuxius
authors.affiliation: Department of Urology, Hospital Ludwigshafen, Ludwigshafen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Müller
authors.affiliation: Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.affiliation: Department of Medical Statistics, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Christel
authors.initials: C
authors.lastname: Weiß
authors.affiliation: Department of Urology, University Hospital Goettingen, Goettingen, Germany.
authors.forename: Elmar
authors.initials: E
authors.lastname: Heinrich
mesh_terms: D000069501:Abiraterone Acetate / Q000494:pharmacology / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D053379:Chromogranin A / Q000097:blood*; D018450:Disease Progression; D000077143:Docetaxel; D019886:Gastrin-Releasing Peptide / Q000097:blood*; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D053379:Chromogranin A; D043823:Taxoids; D000077143:Docetaxel; D019886:Gastrin-Releasing Peptide; D010751:Phosphopyruvate Hydratase; D000069501:Abiraterone Acetate
keywords: chromogranin A; neuroendocrine differentiation (NED); neuroendocrine markers; neuron-specific enolase; pro-gastrin releasing peptide; sequential therapy