Predictive value of low testosterone concentrations during and prior to enzalutamide treatment in metastatic castration-resistant prostate cancer.

ABSTRACT

BACKGROUND: Enzalutamide is an effective treatment for metastatic castration-resistant prostate cancer (mCRPC) patients. However, variances in responses are observed and there is a need for biomarkers predicting treatment outcome and selection. In this study, we aimed to explore the predictive value of testosterone for first-line enzalutamide treatment of mCRPC. METHODS: A retrospective analysis of 72 mCRPC patients with no prior abiraterone or docetaxel treatment was performed. Serum testosterone was measured using a liquid chromatography tandem-mass spectrometry method. Association of pre- and during-enzalutimide treatment testosterone levels with progression-free survival (PFS) and failure-free survival (FFS) was investigated using univariate and multivariate Cox models. Testosterone levels were dichotomized into a low (Q1) and high (interquartile range-Q4) group. RESULTS: Median PFS (7.4 v. 20.8 months, P<0.0001) and FFS (6.6 v. 17.7 months, P<0.0001) were shorter for patients with low testosterone levels (<0.217 nmol/L) during enzalutamide treatment. Furthermore, univariate Cox proportional hazards models revealed that low testosterone levels were associated with shorter PFS (HR 3.5, 95%CI 1.9-6.3; P<0.001) and FFS (HR 3.1, 95%CI 1.7-5.5; P<0.001). Pre-treatment testosterone levels were lower than during-treatment levels (P<0.0001) and low pre-treatment testosterone levels (<0.143 nmol/L) were associated with shorter median PFS (12.6 v. 20.5 months, P<0.01) and FFS (12.6 v. 22.5 months, P<0.01). CONCLUSION: The results of this study suggest that low serum testosterone levels during and prior to enzalutamide treatment can predict progression in mCRPC patients and identifies tumors resistant to next-in-line enzalutamide treatment. Validation in a prospective cohort is warranted.