Clinical implications of endogenous testosterone density on prostate cancer progression in patients with very favorable low and intermediate risk treated with radical prostatectomy

: We tested the association between endogenous testosterone density (ETD; the ratio between endogenous testosterone [ET] and prostate volume) and prostate cancer (PCa) aggressiveness in very favorable low- and intermediate-risk PCa patients who underwent radical prostatectomy (RP). Only patients with prostate-specific antigen (PSA) within 10 ng ml-1, clinical stage T1c, and International Society of Urological Pathology (ISUP) grade group 1 or 2 were included. Preoperative ET levels up to 350 ng dl-1 were classified as abnormal. Tumor quantitation density factors were evaluated as the ratio between percentage of biopsy-positive cores and prostate volume (biopsy-positive cores density, BPCD) and the ratio between percentage of cancer invasion at final pathology and prostate weight (tumor load density, TLD). Disease upgrading was coded as ISUP grade group >2, and progression as recurrence (biochemical and/or local and/or distant). Risk associations were evaluated by multivariable Cox and logistic regression models. Of 320 patients, 151 (47.2%) had intermediate-risk PCa. ET (median: 402.3 ng dl-1) resulted abnormal in 111 (34.7%) cases (median ETD: 9.8 ng dl-1 ml-1). Upgrading and progression occurred in 109 (34.1%) and 32 (10.6%) cases, respectively. Progression was predicted by ISUP grade group 2 (hazard ratio [HR]: 2.290; P = 0.029) and upgrading (HR: 3.098; P = 0.003), which was associated with ISUP grade group 2 (odds ratio [OR]: 1.785; P = 0.017) and TLD above the median (OR: 2.261; P = 0.001). After adjustment for PSA density and body mass index (BMI), ETD above the median was positively associated with BPCD (OR: 3.404; P < 0.001) and TLD (OR: 5.238; P < 0.001). Notably, subjects with abnormal ET were more likely to have higher BPCD (OR: 5.566; P = 0.002), as well as TLD (OR: 14.998; P = 0.016). Independently by routinely evaluated factors, as ETD increased, BPCD and TLD increased, but increments were higher for abnormal ET levels. In very favorable cohorts, ETD may further stratify the risk of aggressive PCa.