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

Abstract

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.

A prospective study of the relationship between CRPC patient's quality of life after enzalutamide and serum testosterone levels measured via LC‐MS/MS

“…Lolli et al reported that changes in AR gene copy numbers and a T level < 0.09 nmol/L were associated with a poor prognosis, and a poor response to ENZ and abiraterone 18 . In our previous studies, higher blood androgen levels before ENZ treatment were associated with higher therapeutic efficacy and less frequent adverse events, such as anorexia, malaise, and fatigue 12 . Of the total population of 95 patients, 75 who had responded to treatment for at least 16 weeks were evaluated.…”

“…18 In our previous studies, higher blood androgen levels before ENZ treatment were associated with higher therapeutic efficacy and less frequent adverse events, such as anorexia, malaise, and fatigue. 12 Of the total population of 95 patients, 75 who had responded to treatment for at least 16 weeks were evaluated. The results showed that, in the High-T group, a good QoL score was maintained, although the difference from the Low-T group was not significant in the analysis including only patients who had responded well to treatment.…”

“…Therefore, we postulated that T, the blood levels of which are expected to be reduced in CRPC patients, may also influence QoL. Our research group has been exploring the possibility that high androgen levels before ENZ treatment predict the treatment response 12 . This prospective study was performed to determine the correlation between pretreatment blood T levels and QoL changes in CRPC patients treated with ENZ.…”

The utility of the [−2]pro‐prostate‐specific antigen level as a prognostic marker in patients with castration‐resistant prostate cancer treated with enzalutamide

“…[23][24][25] Our prospective study showed that blood androgen levels predicted drug efficacy. 21 Loli et al found that changing circulatory AR gene copy number and testosterone values <0.09 nmol/L were associated with poor outcomes and poor response to ENZ and abiraterone. 26 Recently, analyses of circulating tumor cells revealed that patients with amplified AR-related genes responded poorly to AR-targeting drugs such as abiraterone and ENZ.…”

“…We prospectively investigated 104 CRPC patients treated at the Department of Urology of Gunma University Hospital and affiliated hospitals between 2014 and 2018. 21 All patients received enzalutamide. We subjected samples collected during the prospective study to retrospective analysis using prognosis-related data obtained before and after treatment.…”