A Prospective Study of the Relationship Between Clinical Outcomes After Enzalutamide and Serum Androgen Levels Measured via Liquid Chromatography-tandem Mass Spectrometry in Patients with Castration-resistant Prostate Cancer.

Background Enzalutamide (ENZ) is used to treat patients with castration-resistant prostate cancer (CRPC). However, the kinetics of serum androgens before and after ENZ treatment are unknown. Objective To elucidate the kinetics of serum androgens and explore the possibility of identifying a useful marker for predicting the effects of ENZ. Design setting and participants We conducted a prospective study from 2014 to 2018 at Gunma University Hospital and related facilities. Data were analyzed for 104 patients with CRPC treated with ENZ. Outcome measurements and statistical analysis We measured serum androgen levels using liquid chromatography-tandem mass spectrometry. Relationships with outcomes were assessed using multivariable Cox regression and log-rank analyses. Results and limitations The median age of the patients was 73 yr. Median serum testosterone, dihydrotestosterone (DHT), androstenedione, and dehydroepiandrosterone sulfate levels were 49.0, 5.8, 222.2, and 326.3 pg/ml, respectively. We performed multivariate analysis using Cox regression to predict prostate-specific antigen progression-free survival (PSA-PFS) and overall survival (OS). Hemoglobin level (≥12.5 vs <12.5 g/dl), docetaxel treatment history (no vs yes), and DHT level (≥5.9 vs <5.9 pg/ml) were significant predictors of PSA-PFS (p <  0.05). Eastern Cooperative Oncology Group performance status (0 vs. 1-2), hemoglobin level (≥12.5 vs <12.5 g/dl), presence of visceral metastasis (no vs yes), amount of bone metastasis (extent of disease 0-2 vs 3-4), and docetaxel treatment history (no vs yes) were significant predictors of OS (p <  0.05). Binomial logistic analysis of the predictors of any grade of anorexia, malaise, and fatigue showed that the presence of visceral metastasis and a low DHT level (<5.9 pg/ml) were significant. Conclusions Our results suggest that serum androgen levels before ENZ treatment may be useful for predicting efficacy, prognosis, and the incidence of adverse events. Patient summary We measured blood levels of testosterone and other male hormones before treatment with enzalutamide among men with prostate cancer resistant to castration. We found that the levels of these hormones may be useful for predicting the efficacy of enzalutamide treatment, prognosis, and the occurrence of adverse side effects.