Preoperative endogenous testosterone density predicts disease progression from localized impalpable prostate cancer presenting with PSA levels elevated up to 10 ng/mL

OBJECTIVE: To investigate endogenous testosterone density (ETD) predicting disease progression from clinically localized impalpable prostate cancer (PCa) presenting with prostate-specific antigen (PSA) levels elevated up to 10 ng/mL and treated with radical prostatectomy. MATERIALS AND METHODS: In a period ranging from November 2014 to December 2019, 805 consecutive PCa patients who were not under androgen blockade had endogenous testosterone (ET, ng/dL) measured before surgery. ETD was evaluated as the ratio of ET on prostate volume (PV). Unfavorable disease was defined as including ISUP ≥ 3 and/or seminal vesicle invasion in the surgical specimen. The risk of disease progression was evaluated by statistical methods. RESULTS: Overall, the study selected 433 patients, of whom 353 (81.5%) had available follow-up. Unfavorable disease occurred in 46.7% of cases and was predicted by tumor quantitation features that were positively associated with ETD. Disease progression, which occurred for 46 (13%) cases, was independently predicted only by ETD (hazard ratio, HR = 1.037; 95% CI 1.004–1.072; p = 0.030) after adjusting for unfavorable disease. According to a multivariate model, ETD above the third quartile was confirmed to be an independent predictor for PCa progression (HR = 2.479; 95% CI 1.355–4.534; p = 0.003) after adjusting for unfavorable disease. The same ETD measurements, ET mean levels were significantly lower in progressing cancers. CONCLUSIONS: In this particular subset of patients, increased ETD with low ET levels, indicating androgen independence, resulted in a more aggressive disease with poorer prognosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11255-022-03366-3.