Elevated periprostatic testosterone linked to prostate cancer recurrence

Recent findings published in The Journal of Clinical Investigation suggest that a significant number of men with prostate cancer have unappreciated elevated periprostatic venous testosterone, which was found to be associated with worse clinical outcomes following radical prostatectomy.¹

The investigators obtained blood samples from 266 men undergoing radical prostatectomy from July 2014 to August 2021.

The investigators describe periprostatic testosterone as “sneaky testosterone” because it is not seen or accounted for through a normal blood sample.

According to the authors,¹ the findings “suggest that the true degree of prostatic androgen exposure is missed when only peripheral androgens in venous circulation are measured.”

For the study, the investigators obtained blood samples from 266 men undergoing radical prostatectomy from July 2014 to August 2021. They then compared the level of dorsal testosterone (DT) with the level of peripheral testosterone (PT) and explored the association between the DT/PT ratio and progression-free survival (defined as PSA recurrence or radiation therapy as clinical events).

Data showed that some men had levels of DT that were significantly elevated compared with PT levels (P < .001). Specifically, 20% of men had 2-fold higher levels of DT compared with PT, and 5% of men had 10-fold higher levels of DT. Men with elevated DT levels were also found to have increased levels of isocaproic acid, a byproduct of androgen biosynthesis, and 17-OH-progesterone, a marker of intratesticular testosterone.

“For years, testosterone, T, and its derivative, dihydrotestosterone, DHT, have been known to affect prostate development and drive prostate cancer. However, peripheral blood T levels don’t correlate with prostate cancer risk or severity. This study suggests this might be because some men have veins that directly link the prostate to the testes, enabling higher T and DHT levels in the prostate, potentially leading to aggressive tumors. These venous shunts bypass peripheral circulation, meaning arm vein blood samples do not reflect T and DHT exposure to the prostate,” explained co-author Eric A. Klein, MD, in a news release on the findings.² Klein is the emeritus chair of the Glickman Urological and Kidney Institute at Cleveland Clinic in Cleveland, Ohio.

Further, the investigators found that men who had elevated levels of DT (a DT/PT ratio > 2) were found to have higher rates of PSA persistence compared with patients with similar rates of DT and PT (a ratio < 2) (P = .034). Patients with elevated DT also showed a higher rate of clinical events compared with patients with lower levels (P = .003). The ratio between DT and PT was predictive of post-surgical outcomes even after the investigators accounted for known clinical predictors.

Klein concluded in the news release,² “This and future studies could lead to alternative treatment strategies for urological diseases that are impacted by sneaky testosterone physiology.”

References

1. Alyamani M, Michael P, Hettel D, et al. Elevated periprostatic venous testosterone correlates with prostate cancer progression after radical prostatectomy. J Clin Invest. 2023;133(17):e171117. doi:10.1172/JCI171117

2. Desai Sethi Urology Institute researcher finds “sneaky testosterone” might signal worse outcomes for patients with prostate cancer. News release. University of Miami Health System, Miller School of Medicine. September 1, 2023. Accessed September 5, 2023. https://www.newswise.com/articles/desai-sethi-urology-institute-researcher-finds-sneaky-testosterone-might-signal-worse-outcomes-for-men-with-prostate-cancer?ta=home