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Objective To evaluate the influence of endogenous testosterone density (ETD) on pelvic lymph node invasion (PLNI) in high risk (HR) prostate cancer (PCa) treated with radical prostatectomy (RP) and staged with extended pelvic lymph node dissection (ePLND). Materials and methods ETD was evaluated as the ratio of endogenous testosterone (ET) on prostate volume (PV). HR-PCa was assessed according to the European Association of Urology (EAU) system. The association of ETD and other routinely clinical factors (BPC: percentage of biopsy positive cores; PSA: prostate specific antigen; ISUP: tumor grade system according to the International Society of Urologic Pathology; cT: tumor clinical stage) with the risk of PLNI was assessed by the logistic regression model. Results Overall, 201 out of 805 patients (24.9%) were classified HR and PLNI occurred in 42 subjects (20.9%). On multivariate analysis, PLNI was independently predicted by BPC (OR 1.020; 95% CI 1.006–1.035; p = 0.019), ISUP > 3 (OR 2.621; 95% CI 1.170–5.869; p = 0.019) and ETD (OR 0.932; 95% CI 0.870–0.999; p = 0.045). After categorizing continuous clinical predictors, the risk of PLNI was independently increased by ETD up to the median (OR 2.379; 95% CI 1.134–4.991; p = 0.022), BPC > 50% (OR 3.125; 95% CI 1.520–6.425; p = 0.002) as well as by ISUP > 3 (OR 2.219; 95% CI 1.031–4.776; p = 0.042). Conclusions As ETD measurements decreased, patients were more likely to have PLNI. In HR disease with PLNI, the influence of PCa on ETD should be addressed by higher level studies.

Objectives To evaluate preoperative endogenous testosterone (ET) density (ETD), defined as the ratio of ET on prostate volume, and tumor upgrading risk in low-risk prostate cancer (PCa). Materials and methods From November 2014 to December 2019, 172 low-risk patients had ET (nmol/L) measured. ETD, prostate-specific antigen density (PSAD) and the ratio of percentage of biopsy positive cores (BPC) to prostate volume (PV), defined as BPC density (BPCD), were evaluated. Associations with tumor upgrading in the surgical specimen were assessed by statistical methods. Results Overall, 121 patients (70.3%) had tumor upgrading, which was predicted by BPCD (odds ratio, OR = 4.640; 95% CI 1.903–11.316; p = 0.001; overall accuracy: 70.3%). On multivariate analysis, tumor upgrading and clinical density factors related to each other for BPCD being predicted by ETD (regression coefficient, b = 0.032; 95% CI 0.021–0.043; p b = 1.962; 95% CI 1.067–2.586; p b = 0.259; 95% CI 0.112–0.406; p = 0.001). According to the model, as BPCD increased, ETD and PSAD increased, but the increase was higher for upgraded cases who showed either higher tumor load but significantly lower mean levels of either ET or PSA. Conclusions As ETD increased, higher tumor loads were assessed; however, in upgraded patients, lower ET was also detected. ETD might stratify low-risk disease for tumor upgrading features.

Objective To test the hypothesis that endogenous testosterone (ET) density could be associated with tumor load (TL) in patients with intermediate risk (IR) prostate cancer (PCa). Materials and methods Endogenous testosterone density (ETD, ratio between ET and prostate volume [PV]), biopsy positive cores density (BPCD, the ratio between the number of positive cores and PV) and prostate-specific antigen density (PSAD, ratio between total PSA and PV) were retrospectively evaluated on a prospectively collected data on 430 patients with IR PCa submitted to radical prostatectomy (RP). Tumor load (TL) was measured as the percentage of prostatic volume occupied by cancer at final pathology. Unfavorable disease (UD) was defined as tumor upgrading (ISUP grading group 4, 5) and/or upstaging (pT3a or 3b) in prostate specimens. Associations were assessed by the logistic regression and linear regression models. Results Overall, UD, which was detected in 122 out of 430 IR patients (28.4%), was predicted by BPCD (odd ratio, OR = 1.356; 95% CI 1.048–1.754; p = 0.020) with a sensitivity 98.4% and overall accuracy 71.9%. On multivariate analysis, BPCD was independently predicted by PSAD (regression coefficient, b = 1.549; 95% CI 0.936–2.162; p b = 0.032; 95% CI 0.023–0.040; p b = 0.009; 95% CI 0.005–0.014; p 1.0%/mL had significantly lower ET levels. Conclusions As ETD increased, BPCD and TL increased, accordingly; furthermore, patients with lower ET levels were more likely to have occult UD. The influence of tumor load, and unfavorable disease on ET and ETD needs to be addressed by further studies.

Objective To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND). Materials and methods Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N = 0) or with one (N = 1) or more than one metastatic node (N > 1). The risk of multiple pelvic lymph node metastasis (N > 1, mPLNM) was assessed by comparing it to the other two groups (N > 1 vs. N = 0 and N > 1 vs. N = 1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT > 1) and tumor grade group greater than two (ISUP > 2). Results Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N = 1 and 31 (5%) with N > 1. On multivariate analysis, ET was inversely associated with the risk of N > 1 when compared to both N = 0 (odds ratio, OR 0.997; CI 0.994–1; p = 0.027) as well as with N = 1 cases (OR 0.994; 95% CI 0.989–1.000; p = 0.015). Conclusions In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

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.

To evaluate the association between basal total testosterone (TT) levels with the European Association of Urology (EAU) risk classes at the time of diagnosis of prostate cancer (PCA). A retrospective review of prospectively collected data was carried out between November 2014 and March 2018. Preoperative basal TT levels and PSA were measured in 601 consecutive Caucasian patients who were not under androgen deprivation and undergoing surgery at a tertiary referral center. Patients were classified into low (reference group), intermediate- and high-risk/locally advanced classes. The multinomial logistic regression model evaluated associations of TT and other clinical factors with EAU risk classes. One hundred twenty four patients (24%) were low risk, 316 (52.6%) were intermediate, 199 (16.5%) were high risk and 42 (7%) were locally advanced. Median circulating basal TT levels increased along EAU classes. TT, PSA, percentage of biopsy-positive cores and tumor clinical stage were independently associated with the high-risk class (odds ratio, OR = 1.002; p = 0.030) but were not associated with intermediate-risk or locally advanced PCA when compared to the low-risk class. TT above the median value was an independent predictor of high-risk class PCA. Basal TT levels are positively associated with low, intermediate and high EAU risk classes. The association is significant for the high-risk class when compared to the low-risk group, but was lost in locally advanced risk class. In PCA patients, high TT serum levels are associated with high-risk disease. Endogenous TT should be considered as a biological marker for assessing EAU PCA risk classes.

To investigate the associations of endogenous testosterone with prostate growing disorders (PGD) including benign prostatic hyperplasia (BPH) and prostate cancer (PCA). The study population was composed by 1176 cases including 371 BPH subjects (31.5%) without cancer who underwent prostate transurethral resection from January 2017 to November 2019 and 805 patients (68.5%) with PCA who underwent surgery from November 2014 to December 2019. The association of endogenous testosterone, which was measured before surgery, with the risk of PGD was evaluated by statistical methods. In the study population, endogenous testosterone levels were significantly lower in PCA cases compared to BPH patients who were older with larger prostates but lower prostate-specific antigen (PSA) levels. On multivariate analysis, the risk of PCA decreased by endogenous testosterone (odds ratio, OR = 0.957; 95% CI 0.930–0.984; p = 0.002) as by age (OR = 0.955; 95% CI 0.933–0.984; p

To evaluate the association between obesity and risk of multiple lymph node metastases in prostate cancer (PCa) patients with clinically localized EAU intermediate and high-risk classes staged by extended pelvic lymph-node dissection (ePLND) during robot assisted radical prostatectomy (RARP). 373 consecutive PCa intermediate or high-risk patients were treated by RARP and ePLND. According to pathology results, extension of LNI was classified as absent (pN0 status) or present (pN1 status); pN1 was further categorized as one or more than one (multiple LNI) lymph node metastases. A logistic regression model (univariate and multivariate analysis) was used to evaluate the association between significant categorized clinical factors and the risk of multiple lymph nodes metastases. Overall, after surgery lymph node metastases were detected in 51 patients (13.7%) of whom 22 (5.9%) with more than one metastatic lymph node and 29 (7.8%) with only one positive node. Comparing patients with one positive node to those without, EAU high-risk class only predicted risk of single LNI (OR = 2.872; p = 0.008). The risk of multiple lymph node metastases, when compared to cases without LNI, was independently predicted by BMI ≥ 30 (OR = 6.950; p = 0.002) together with BPC ≥ 50% (OR = 3.910; p = 0.004) and EAU high-risk class (OR = 6.187; p