Abstract
Generally, clinical assessment of gonadal testosterone (T) in human physiology is determined using concentrations measured in peripheral blood. Prostatic T exposure is similarly thought to be determined from peripheral T exposure. Despite the fact that androgens drive prostate cancer, peripheral T has had no role in clinical evaluation or treatment in men with localized prostate cancer.
To assess the role of local androgen delivery in prostate cancer, we obtained blood from the (periprostatic) prostatic dorsal venous complex in 266 men undergoing radical prostatectomy from July 2014-August 2021 and compared dorsal T levels (DT) to those in circulating peripheral blood (PT) and prostatic tissue. Comprehensive targeted steroid analysis and unbiased metabolomics analyses were performed. The association between DT/PT ratio and progression-free survival after prostatectomy was assessed.
Surprisingly, in some men, DT was enriched several-fold compared with PT. For example, 20% of men had local T concentrations at least 2-fold higher than peripheral T. Isocaproic acid, a byproduct of androgen biosynthesis and 17-OH-progesterone, a marker of intratesticular testosterone, were also enriched in the dorsal vein of these men, consistent with testicular shunting. Men with enriched DT had higher rates of recurrence. DT/PT concentration ratios predicted worse outcomes even when accounting for known clinical predictors.
These data suggest a large proportion of men have a previously unappreciated exposure to undiluted and highly concentrated T supply. Elevated periprostatic T exposure is associated with worse clinical outcomes after radical prostatectomy.