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.
PATIENTS AND METHODS - Chromogranin A (CGa) and neuron-specific enolase (NSE) were determined in serum drawn before treatment with abiraterone of 45 mCRPC patients. Outcome measures were overall survival (OS), prostate-specific antigen (PSA) response defined by PSA decline ≥50%, PSA progression-free survival (PSA-PFS) and clinical or radiographic PFS.
RESULTS - CGa and NSE serum levels did not correlate (p=0.6). Patients were stratified in a low (n=9), intermediate (n=18) or high (n=18) risk group according to elevation of none, one or both neuroendocrine markers. 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 - CGa and NSE did not predict PSA response in mCRPC patients 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. This article is protected by copyright. All rights reserved.
BJU international. 2016 Mar 31 [Epub ahead of print]
Matthias M Heck, Markus A Thaler, Sebastian C Schmid, Anna-Katharina Seitz, Robert Tauber, Hubert Kübler, Tobias Maurer, Mark Thalgott, Georgios Hatzichristodoulou, Michael Höppner, Roman Nawroth, Peter B Luppa, Jürgen E Gschwend, Margitta Retz
Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Institute of Clinical Chemistry and Pathobiochemistry, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany., Department of Urology, Klinikum rechts der Isar, Technical University of Munich, Germany.