title: Chromogranin A and neurone-specific enolase serum levels as predictors of treatment outcome in patients with metastatic castration-resistant prostate cancer undergoing abiraterone therapy.
abstract: OBJECTIVE
  To determine the impact of elevated neuroendocrine serum markers on treatment outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment with abiraterone in a post-chemotherapy setting.
  
  
  METHODS
  Chromogranin A (CGa) and neurone-specific enolase (NSE) were determined in serum drawn before treatment with abiraterone from 45 patients with mCRPC. Outcome measures were overall survival (OS), prostate-specific antigen (PSA) response defined by a PSA level decline of ≥50%, PSA progression-free survival (PSA-PFS), and clinical or radiographic PFS.
  
  
  RESULTS
  The CGa and NSE serum levels did not correlate (P = 0.6). Patients were stratified in to low- (nine patients), intermediate- (18) or high-risk (18) groups according to elevation of none, one, or both neuroendocrine markers, respectively. The risk groups correlated with decreasing median OS (median OS not reached vs 15.3 vs 6.6 months; P < 0.001), decreasing median clinical or radiographic PFS (8.3 vs 4.4 vs 2.7 months; P = 0.001) and decreasing median PSA-PFS (12.0 vs 3.2 vs 2.7 months; P = 0.012). In multivariate Cox regression analysis the combination of CGa and NSE (≥1 marker positive vs both markers negative) remained significant predictors of OS, clinical or radiographic PFS, and PSA-PFS. We did not observe a correlation with PSA response (63% vs 35% vs 31%; P = 0.2).
  
  
  CONCLUSIONS
  Chromogranin A and NSE did not predict PSA response in patients with mCRPC treated with abiraterone. However, we observed a correlation with shorter PSA-PFS, clinical or radiographic PFS, and OS. This might be due to an elevated risk of developing resistance under abiraterone treatment related to neuroendocrine differentiation.
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Matthias M
authors.initials: MM
authors.lastname: Heck
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Thaler
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Sebastian C
authors.initials: SC
authors.lastname: Schmid
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: Seitz
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Tauber
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kübler
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Maurer
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Thalgott
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Hatzichristodoulou
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Höppner
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Nawroth
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Luppa
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Jürgen E
authors.initials: JE
authors.lastname: Gschwend
authors.affiliation: Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Retz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000736:Androstenes / Q000627:therapeutic use*; D053379:Chromogranin A / Q000097:blood*; D018572:Disease-Free Survival; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010751:Phosphopyruvate Hydratase / Q000097:blood*; D011237:Predictive Value of Tests; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood* / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000736:Androstenes; D053379:Chromogranin A; D017430:Prostate-Specific Antigen; D010751:Phosphopyruvate Hydratase; C089740:abiraterone
keywords: abiraterone; castration-resistant prostate cancer; chromogranin A; neuroendocrine prostate cancer; neuron-specific enolase