Abstract 1418P
Background
The impact of castration on levels of steroid precursors of active androgens (testosterone or dihydrotestosterone (DHT)) is not well-characterized. We report the modulation by castration of gonadal and extragonadal androgen precursor steroids and their association with DHT and testosterone levels.
Methods
116 serum samples were collected from 99 prostate cancer patients and categorized either as eugonadal, castration-sensitive (CSPC), castration-resistant (CRPC) or CRPC under abiraterone acetate. Serum levels of 15 steroids were measured using mass spectrometry and compared between groups using ANOVA. Intrapatient association of steroid levels and the androgens testosterone and DHT were assessed using Pearson correlation and linear regression.
Results
Testosterone, DHT, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androsterone, androstenediol, estrone, estrone-sulfate, estradiol, androsterone/3α-diol-3/3α-diol-17-glucuronide levels were statistically significantly decreased in CSPC compared to eugonadal (treatment-naïve) patients. Testosterone levels were strongly associated with multiple steroids under eugonadal conditions, whereas they were sparsely affected by precursor steroids in castrated patients. By contrast, DHT levels under androgen deprivation therapy (ADT) were associated with testosterone and the backdoor pathway metabolite androsterone. In CRPC patients, levels of androstenedione were significantly associated with testosterone level, while testosterone was the only steroid which predicted DHT levels.
Conclusions
ADT significantly reduces the levels of 13 circulating steroids. Upon ADT initiation, the backdoor pathway metabolite androsterone strongly predicted DHT levels. Under CRPC conditions, androstenedione was significantly associated with testosterone levels suggesting the presence of tumor-related circulating androgens in these patients. These results provide further rationale to intensify treatments with androgen receptor axis signalling pathway inhibitors in patients with prostate cancer.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
CHU Quebec-Université Laval.
Funding
Sanofi.
Disclosure
F. Pouliot: Financial Interests, Personal, Stocks/Shares: Allogene Therapeutics; Financial Interests, Personal, Advisory Role: Tersera, Janssen, Astellas, Bayer, Tolmar, Merck, Novartis Company; Financial Interests, Personal, Speaker’s Bureau: Tolmar; Financial Interests, Institutional, Funding: Astellas, Janssen, Bayer. P. Toren: Financial Interests, Institutional, Funding: AstraZeneca, TerSera; Financial Interests, Personal, Advisory Role: AbbVie, Bayer, Ferring, Sanofi. L. Lacombe: Financial Interests, Institutional, Funding: Amgen, Astellas, Bayer, Janssen, Merck, BMS, Roche, Pfizer, AstraZeneca, Sanofi, Telix, Incyte, Calithera, Myovant, MedImmune. All other authors have declared no conflicts of interest.