Growth-Differentiation-Factor 15 (GDF15) and Hepcidin as Prognostic Biomarkers for Abiraterone-Treated Metastatic Castration-Resistant Prostate Cancer.

Abstract

Background: Since 2004, several agents prolonging OS in mCRPC have expanded the therapeutic spectrum. Abiraterone is part of the standard of care. Nevertheless, CRPC remains fatal, highlighting the need for new biomarkers to customize the constantly growing treatment choices and sequences to individual patients.

Methods: We retrospectively analyzed serum and demographic data of 28 consecutive patients with mCRPC treated with abiraterone. Baseline serum GDF15 and hepcidin were measured prior to treatment initiation. Because both biomarkers showed right-skewed distributions, they were analyzed as continuous, natural log-transformed variables in Cox regression analyses. Kaplan-Meier analyses using median splits were performed to visualize survival differences. Associations with PFS and OS were examined using univariate and multivariate Cox regression analyses. Multivariate analysis included GDF15, prostate specific antigen-decline by 50% (PSA50) and visceral metastases.

Results: Higher baseline ln-transformed GDF15 levels were associated with shorter PFS (HR 1.6; P = .04) and OS (HR 1.8; P < .01) in univariate analysis. Median split Kaplan-Meier analysis showed shorter PFS (8 vs. 13 months, P < .01) and OS (12 vs. 42 months, P < .01) in patients with higher GDF15. In multivariate analyses GDF15 remained independently associated with OS (HR 1.8; P = .01) after adjustment for PSA50 and visceral metastases, whereas the association with PFS was no longer statistically significant. No significant associations between baseline hepcidin and PFS or OS were found.

Conclusion: Higher baseline serum GDF15 was associated with poor outcomes in patients with mCRPC treated with abiraterone. Further validation as a candidate prognostic biomarker in prospective studies involving larger, independent patient cohorts is recommended.