Endogenous testosterone density associates with predictors of tumor upgrading and disease progression in the low through favorable intermediate prostate cancer risk categories: analysis of risk factors and clinical implications

Background The study aimed to test the hypothesis that endogenous testosterone density (ETD), in the low through favorable intermediate PCa risk classes patients undergoing surgery, might be associated with disease progression. Materials and methods ETD, PSAD, and percentage of biopsy positive cores density (BPCD) were calculated in relation to prostate volume (PV). Tumor load density (TLD) was estimated as the tumor load (TL) ratio to prostate weight. ET was considered low if < 230 ng/dL. Tumor upgrading (ISUP > 2), upstaging (pT > 2) and their related features were investigated. Results 433 patients were included, 249 (57.5%) from the favorable intermediate-risk class. Upgrading occurred in 168 (38.8%) cases and upstaging in 62 (14.3%). ETD above the median (9.9 ng/(dL x mL)), was discriminated by PSAD (AUC = 0.719; 95% CI: 0.671–0.766; p < 0.0001), BPCD (AUC = 0.721; 95% CI: 0.673–0.768; p < 0.0001), TLD (AUC = 0.674; 95% CI: 0.624–0.724; p < 0.0001) with accuracy improved by the multivariable model (AUC = 0.798; 95% CI: 0.724–0.811; p < 0.0001). In linear multivariable models as ETD increased, so did TLD (rc = 0.019; 95% CI: 0.014; 0.025; p < 0.0001), further increased by low ET (rc = 0.097; 95% CI: 0.017; 0.176; p = 0.017). After adjusting for clinical and pathological features, ETD correlated with TLD above the first quartile. Disease progression occurred in 43 (11.9%) patients, independently predicted by PSAD (hazard ratio, HR = 99.906; 95% CI: 6.519–1531.133; p = 0.001) and tumor upgrading (HR = 3.586; 95% CI: 3.586–6.863; p < 0.0001). Conclusions ETD was associated with unfavorable PCa, and men with tumor upgrading were at increased risk of disease progression. ETD was related to predictors of PCa progression and could provide pivotal biological information about aggressive disease.