High 11-ketotestosterone linked to shorter time to castration resistance in recurrent non-metastatic prostate cancer.

Abstract

The contribution of 11-oxygenated androgens to the progression of lethal prostate cancer (PCa) remains unresolved. We hypothesized that evaluating circulating levels of 11-oxygenated androgens, such as the androgen receptor agonist 11-ketotestosterone (11KT), could serve as a potential predictor of the onset of castration resistant prostate cancer (CRPC). We used mass spectrometry to quantify 11-oxygenated androgens in post-operative plasma samples acquired from 145 patients who subsequently received androgen deprivation therapy (ADT) for biochemical recurrence (BCR) and achieved castrated testosterone (T) levels. Kaplan-Meier survival analyses and multivariable Cox models were used to investigate relationships between steroids and CRPC. Of 145 patients, 31 developed CRPC with a median time to CRPC of 57 months. 11-oxygenated androgens levels were unaffected by ADT, which stands in contrast to the observed changes in T and other steroids. 11KT was the most abundant androgen but was not linked to clinical features. Kaplan-Meier analysis revealed that 11KT levels above the median of 273 pg/mL were associated with a shorter time to CRPC (P = 0.03). In multivariable analyses, this was supported with an adjusted hazard ratio of 2.17 (95% confidence interval (CI) 0.99-4.71; P = 0.05). 11KT is a key component of the hormonal profile predictive of earlier onset of CRPC. Enhancing our understanding of the specific role of 11KT in the progression to CRPC could help optimize hormonal therapy for castration sensitive PCa and CRPC patients.