LAUSR

BACKGROUND Starting in the 1940s, testosterone was largely assumed to stimulate growth of prostate cancer (PCa). In the past two decades, however, the role of testosterone in men with PCa has been questioned, suggesting the need for its reexamination. OBJECTIVE To comprehensively assess total and calculated free testosterone levels in a consecutive group of PCa patients and any potential impact on disease aggressiveness and recurrence outcomes Participants and Methods Single center prospective cohort of 882 patients presenting for radical prostatectomy, from 2009-2018. Total testosterone (TT), sex hormone binding globulin (SHBG), and calculated free testosterone (cFT) were prospectively collected. Stepwise logistic regression models were used to assess correlation of TT and cFT with pathologic Gleason Grade Group (GGG), extraprostatic extension (EPE), seminal vesicle invasion (SVI), and biochemical recurrence (BCR). RESULTS AND LIMITATIONS TT remained nearly constant across decades (40s-80s): 0.09 decrease/year, R=0.02, while SHBG increased 0.87/year, R=0.32 and cFT decreased 0.08/ year, R=-0.02. Low cFT<5.5 independently predicted: very high-risk GGG (OR=0.435, 95%CI: 0.846-0.994, p=0.036), EPE (OR=0.557, 95%CI: 0.810-0.987, p=0.011), SVI (OR=0.396, 95%CI: 0.798-1.038, p=0.059), and BCR within 1 year postRARP (OR=0.638, 95%CI: 0.971-3.512, p=0.046). TT was not a predictor. CONCLUSION In contrast to popular belief, testosterone remained stable as men aged 40-80 years, whereas free testosterone decreased 2-3%/year. Low cFT was an independent predictor of very high risk prostate cancers and BCR.