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This is a critical review of the current literature data about sexual dysfunction as a potential side effect related to drugs commonly used for the treatment of Benign Prostatic Hyperplasia and Lower Urinary Tract Symptoms. In this narrative review, we analyzed data from the literature related to the development of sexual dysfunctions during the treatment of BPH or LUTS. Both α-blockers and 5-alpha reductase inhibitors (5-ARIs) can induce erectile dysfunction, ejaculatory disorders and a reduction in sexual desire. The sexual side effect profile of these drugs is different. Among the α-blockers, silodosin appears to have the highest incidence of ejaculatory disorders. Persistent sexual side effects after the discontinuation of finasteride have been recently reported; however, further studies are needed to clarify the true incidence and the significance of this finding. However, most of the published studies are affected by a weak methodology and other important limitations, with only a few RCTs available. Therefore, it is desirable that future studies will include validated tools to assess and diagnose the sexual dysfunction induced by these medications, especially for ejaculation and sexual desire disorders.

Objective To identify significant clinical factors associated with prostate cancer (PCa) upgrading the low-risk PCa patients graded according to the modified Gleason score system. Materials and methods The logistic regression model was used to evaluate the records of 438 patients. Results There were 170 cases (38.8%) of low-risk PCa and tumors were upgraded in 111 patients (65.3%). Only prostate specific antigen (PSA) and the proportion of positive cores (P+) were independent predictors of tumor upgrading. Further exploration was investigated by categorizing and regressing PSA (≤ 5.0 vs. > 5.0 ng/ml) and P+ (≤ 0.20 vs. > 0.20). The odds ratio of PSA > 5 ng/ml was 1.32 and of P+ > 0.20 was 2.71. The population was stratified into very low-risk with PSA ≤ 5 ng/ml and P+ ≤ 0.20 (class A), low-risk with PSA > 5 ng/ml and P+ ≤ 0.20 (class B), intermediate risk with PSA ≤ 5 ng/ml and P+ > 0.20 (class C), and high risk with PSA > 5 ng/ml and P+ 0.20 (class D). Upgrading rates were extremely low in class A (9%), extremely high in D (50.5%), and moderate (20%) in B and C. Conclusion Patients diagnosed with low-risk PCa at biopsy are a heterogeneous population because they include subsets with undetected high-grade disease. Significant clinical predictors of upgrading include the PSA value and P+. In low-risk PCa, we identified a high-risk upgrading subgroup that needed repeat biopsies in order to reclassify the tumor grade and to reassess the clinical risk category.

To investigate the associations, if any, between preoperative plasma levels of total testosterone (TT) and pathology Gleason score (pGS) in a contemporary cohort of prostate cancer (PCa) patients.Between November 2014 and June 2015, plasma levels of TT were measured in 142 patients who underwent radical prostatectomy. Exclusion criteria were as follows: 5α-reductase inhibitors, LH-releasing hormone analogues, or testosterone replacement treatment. The entire cohort, assessed by continuous and categorical variables, was classified into two groups according to the pGS that included low-intermediate (pGS 6-7) and high grade (pGS7) cases. TT was evaluated as a continuous variable.The cohort included 128 cases. High grade PCa was detected in 28 (21.8%) patients. Median plasma levels of both TT and prostate specific antigen (PSA) were significantly higher in these cases. In the clinical multivariate model, independent and positive predictors of pGS7 were TT (p = 0.041; OR = 1.004), PSA (p = 0.006; OR = 1.191), and bGS6 (p = 0.004; OR = 5.0); that is, a single unit increase in TT plasma levels increases the odds of having high grade PCa by 4%.In a contemporary cohort of patients, preoperative plasma levels of TT directly and independently associated with high grade PCa. High baseline plasma levels of TT might have clinical applications for managing PCa. New and well designed prospective studies dealing with this subject are required.

This paper presents the results of a pilot study of difficult-to-treat patients (exhibiting several previous treatment failures or detection of extended-spectrum beta-lactamase [ESBL] strains) with chronic bacterial prostatitis (CBP) who underwent treatment with fosfomycin trometamol (FT) and N-acetyl-L-cysteine (NAC). Twenty-eight patients with clinically- and microbiologically-confirmed CBP who attended a single urological institution between January 2018 and March 2019 were treated with oral administration of 3 g FT once a day for 2 days, followed by a dose of 3 g every 48 h for 2 weeks, in combination with oral administration of NAC 600 mg once a day for 2 weeks. Clinical and microbiological analyses were carried out at the time of admission (T0) and during follow-up at 1 month (T1) and 6 months (T2) after the end of treatment. Symptoms were assessed by the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and International Prostatic Symptom Score (IPSS), and quality of life was assessed by Quality of Well-Being (QoL) questionnaires. Isolated strains were Escherichia coli (23 patients), Enterococcus spp. (3 patients), and Klebsiella oxytoca (2 patients). ESBL strain was found in 19 (67.8%) patients. Microbiological eradication was documented in 21 (75%) patients at the second follow-up visit and clinical cure was achieved in 20 (71.4%) patients. Significant changes on questionnaires were recorded between baseline and follow-up visits. Fifteen of 19 patients (78.9%) with ESBL strains were cured. No significant side effects were reported. FT in combination with NAC is a promising alternative therapy in difficult-to-treat CBP patients.

Inflammation is inherent in prostatic diseases and it is now accepted that it may facilitate cellular proliferation in both benign and malignant conditions. The strong relationship between prostatic inflammation and pathogenesis of benign prostatic hyperplasia (BPH) is supported by epidemiologic, histopathologic and molecular evidence. Contrariwise, the role of inflammation in prostate carcinogenesis is still controversial, although current data indicate that the inflammatory microenvironment can regulate prostate cancer (PCa) growth and progression. Knowledge of the complex molecular landscape associated with chronic inflammation in the context of PCa may lead to the introduction and optimization of novel targeted therapies. In this perspective, evaluation of the inflammatory component in prostate specimens could be included in routine pathology reports.

Aim To determine clinical factors associated with multiple bilateral lymph node micrometastases and seminal vesicle invasion (pT3b) in organ-confined prostate cancer (PCa). Methods The study excluded patients under androgen deprivation, with lymph node involvement (cN1 status), and having undergone unilateral pelvic lymph node dissection (PLND) during radical prostatectomy (RP). Lymph node micrometastases were classified as unilateral (pN1m) and bilateral (pN1b). Analysis considered multivariate multinomial logistic regression models. Results Between January 2013 and March 2015, 140 patients underwent PLND during RP. Lymph node micrometastases were detected in 28 cases (20%) including pN1m in 19 (13.6%) and pN1b in 9 (6.4%). Independent clinical predictors of pN1b included prostate-specific antigen (PSA, µg/L) >12.5 (odds ratio [OR] = 43.0), proportion of positive biopsy cores (PBC) >0.57 (OR = 6.7), and biopsy Gleason grade (bGG) >3 (OR = 7.5). Independent pT3b predictors included PSA>12.5 (OR = 3.8), PBC>0.57 (OR = 4.1), and bGG>3 (OR = 3.8). Conclusions In cN0 patients with localized PCa undergoing PLND, a nonnegligible rate of multiple lymph node micrometastases was detected (32.2%). In the natural history of PCa, there is a close association between pT3b and pN1b disease. Prostate cancer patients who are at high risk of extraglandular extension need selective pelvic staging by multiparametric magnetic resonance imaging to assess seminal vesicle invasion. Operated patients with pT3b and pNx status need close PSA monitoring because of the high probability of occult multiple bilateral lymph node micrometastases.

Objective To investigate potential associations of preoperative total testosterone (TT) with tumor volume (TV) and grade of prostate cancer (PCa). Methods Patients who were under medications impacting on the hypothalamic-pituitary-adrenal-testis-prostate axis were excluded. TT was measured preoperatively at least 1 month after biopsies and TV was calculated on the removed prostate specimen. Other continuous variables included total prostate specific antigen (PSA), percentage of positive cores (P+) and weight (W) of the removed prostate. Patients were categorized according to the pathologic Gleason score (pGS) in 3 groups (pGS 6, 7 and > 7). Invasion of the seminal vesicles was coded as seminal vesicle invasion (SVI). Results The median levels of TT were significantly and increasingly higher from pGS 6 (14.7 nmol/L) to pGS 7 (15.0 nmol/L) and pGS > 7 (18.8 nmol/L). The median values of TV were also detected significantly and increasingly higher from pGS 6 (5.6 mL) to pGS 7 (8.1 mL) and pGS > 7 (14.8 mL). The median preoperative levels of PSA were also increasing from pGS 6 (5.9 μg/L) to pGS 7 (6.2 μg/L) and pGS > 7 (7.7 μg/L). There was a significant and positive correlation of TV to PSA, TT and P+. Multiple linear regression analysis showed that TV was significantly and independently predicted by TT, PSA and P+. High grade PCa (pGS > 7) independently associated with TV, TT, P+ and SVI. The median density values of TT relative to TV (quotient TT/TV) significantly decreased from pGS 6 (2.6 nmol/L/mL) to pGS 7 (1.9 nmol/L/mL) and pGS > 7 (1.4 nmol/L/mL). The median density values of PSA relative to TV (quotient PSA/TV) also significantly decreased from pGS (1.1 μg/L/mL) to pGS 7 (0.7 μg/L/mL) and pGS > 7 (0.6 μg/L/mL). Conclusion The investigation shows that TT relates to volume and grade of PCa; moreover, the density of TT relative to TV inversely associates with rate of increase of cancer that depends on the grade of the tumour.

Objective: In the last years there is a growing interest in nutraceutical substances that seems able to improve clinical symptoms in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). In this paper, we evaluated both efficacy and safety of a combination of daidzein with isolase and zinc in patients with LUTS due to BPH. Materials and methods: In a phase I-II study clinical trial we enrolled patients with clinical and instrumental diagnosis of LUTS associated to BPH that received a six-month treatment with a combination of daidzein with isolase and zinc (1 tablet/day). Clinical, laboratory and instrumental analyses were carried out at the time of admission (T0) and 6 months after the ending of the treatment (T1). The Italian version of International Prostatic Symptom Score (IPSS), International Index of Erectile Function (IIEF-5) and Quality of Well-Being (QoL) questionnaires were used. The development of adverse drug reactions (ADRs) and drug interactions (DDIs) were recorded using the Naranjo scale and drug interaction probability scale. Student’s t test and Anova test were used for statistical analysis, and the threshold of statistical significance was set at P < 0.05. Results: We enrolled 71 patients, 62 (87.3%) completed the follow-up and we documented a significant differences between T0 and T1 in terms of IPSS [21.5 ± 1.2 vs 16.2 ± 1.5; (-4.8); p < 0.001], Cmax [9.7 ± 3.7 vs 15.3 ± 2.5; (+5.6); p < 0.001] and QoL [0.56 ± 0.15 vs 0.84 ± 0.19; (+0.28); p < 0.001]. In contrast, no significant difference were recorded in terms of IIEF-5 [p = 0.50] and PSA [p = 0.67]. Finally, we did not record any significant ADRs or DDIs during the study. Conclusions: In this study, we documented that a combination of daidzein with isolase and zinc, reduces the clinical symptoms of LUTS and improves the quality of life in patients with BPH, without the development of ADRs or DDIs.

Objectives: To evaluate clinical predictors of disease reclassification or progression (DR/P) in prostate cancer patients elected to active surveillance (AS). Material and Methods: Patients were assessed on the basis of DR/P criteria. Predictors of DR/P were evaluated by multivariate logistic regression and Cox proportional hazards. Results: The median DR/P free time was 16.5 months. DR/P was detected in 30 out of 84 cases (35.7%). In DR/P cases, the median prostate volume (PV) was significantly lower (34.7 vs. 42.7 ml) and the percentage of cases with 2 or 3 vs. 1 initial biopsy positive cores (BPC) was significantly higher (36.7 vs. 7.4%). The multivariate logistic regression model showed that PV (OR 0.9; p = 0.021) and initial n >1 BPC (OR 9.8; p = 0.001) were independent predictors of DR/P. By Cox multivariate proportional hazards, only n >1 BPC predicted early DR/P (hazard ratio 3.1; p = 0.003). Conclusions: In a contemporary cohort of patients elected to AS, independent factors stratifying the risk of DR/P were PV and initial BPC, which also predicted early DR/P. In patients elected to AS, the identification of risk factors of DR/P require early re-biopsy. Confirmatory studies are required.

Objectives: To investigate associations of chronic inflammatory infiltrate (CII) with prostate cancer (PCa) risk and the number of positive cores in patients elected to a first set of biopsies. Materials and Methods: Excluding criteria were as follows: active surveillance, prostate specific antigen (PSA) ≥ 30 ng/l, re-biopsies, incidental PCa, less than 14 cores, metastases, or 5-alpha reductase inhibitors. The cohort study was classified as negative (control group) and positive cores between 1 and 2 or > 2. Results: The cohort included 421 cases who did not meet the exclusion criteria. PCa was detected in 192 cases (45.6%) of which the number of positive cores was between 1 and 2 in 77 (40.1%) cases. The median PSA was 6.05 ng/ml (range 0.3-29 ng/ml). Linear regression models showed that CII was an independent predictor inversely associated with the risk of PCa. Multinomial logistic regression models showed that CII was an independent factor that was inversely associated with PCa risk in cases with positive cores between 1 and 2 (OR = 0.338; p = 0.004) or more than 2 (OR = 0.076; p Conclusion: In a cohort of men undergoing the first biopsy set after prostate assessment, the presence of CII in the biopsy core was an independent factor inversely associated with PCa risk as well as with the number of positive biopsy cores (tumor extension). Clinically, the detection of CII in negative biopsy cores might reduce the risk of PCa in repeat biopsies as well as the probability of detecting multiple positive cores.

Background/Aims/Objectives: In patients elected to the first prostate biopsy set, the risk of prostate cancer (PCA) may be predicted by clinical factors. The aim of this study was to investigate on prostate volume index (PVI), defined as the ratio of volume of the transitional zone to the volume of the peripheral zone, and PCA risk. Methods: The study retrospectively evaluated 1,327 patients and included only the first biopsy set with 14 cores. PCA risk was assessed by using the multivariate logistic regression model. Results: The analysis evaluated 596 patients. The detection rate of PCA was 49%. Age, prostate specific antigen, PVI and digital rectal exam were independent factors of PCA risk, which was decreased by PVI (OR 0.224; 95% CI 0.157-0.380). The goodness of fit statistics assessed model efficacy. Conclusions: In a large cohort undergoing the first biopsy set, PVI associated with a decreased risk of PCA. Confirmatory studies are required.

Purpose: The study aims to investigate the potential associations between preoperative plasma levels of total testosterone (TT) and biopsy Gleason score (bGS) upgrading in prostate cancer (PCA) patients undergoing radical prostatectomy (RP). Materials and Methods: Exclusion criteria were treatment with 5α-reductase inhibitors, LH-releasing hormone analogues or testosterone replacement. Criteria of bGS upgrading were as follows: (i) bGS 6 to pathological Gleason score (pGS) >6, (ii) bGS 7 with pattern 3 + 4 to pGS 7 with pattern 4 + 3 or to pGS >7, (iii) bGS 7 with pattern 4 + 3 to pGS >7. Patients who showed bGS >7 were excluded from the cohort. Results: The study included 209 patients. Tumor upgrading was assessed in 76 (36.4%) cases of the entire cohort, in 51 out of 130 cases (39.2%) of the bGS 6 group and 25 out of 79 patients (31.6%) in the bGS 7 cluster. Logistic regression models showed that independent clinical covariates predicting the risk of bGS upgrading included TT (OR 1.058; p = 0.027) and prostate-specific antigen (PSA) density (OR 23.3; p = 0.008) as well as TT (OR 1.057; p = 0.029) with PSA (OR 1.061; p = 0.023). The model suggests that 1 unit increase in TT plasma levels increases the odds of bGS upgrading by 5.8 or 5.7%. Conclusions: In summary, we have determined that high TT preoperative plasma levels independently predict bGS upgrading in men with PCA undergoing RP. Preoperative plasma levels of TT might be included as a potential marker for assessing the risk bGS upgrading.

Objective: To identify clinical factors associated with prostate cancer (PCA) upgrading to higher patterns of the surgical specimen in low-risk PCA. Materials and Methods: We evaluated the records of 438 patients. The multinomial logistic regression model was used. Results: Low-risk PCA included 170 cases (38.8%) and tumor upgrading was detected in 111 patients (65.3%) of whom 72 (42.4%) had pathological Gleason patterns (pGP) = 3 + 4 and 39 (22.9%) pGP >3 + 4. Prostate-specific antigen (PSA) and proportion of positive cores (P+) were independent predictors of tumor upgrading to higher patterns. The main difference between upgraded cancers related to PSA and to P+ >0.20. The population was stratified into risk classes by PSA ≤5 μg/l and P+ ≤0.20 (class A), PSA >5 μg/l and P+ ≤0.20 (class B), PSA ≤5 μg/l and P+ >0.20 (class C) and PSA >5 μg/l and P+ 0.20 (class D). Upgrading rates to pGP >3 + 4 were extremely low in class A (5.1%), extremely high in D (53.8%). Conclusions: Low-risk PCA is a heterogeneous population with significant rates of undetected high-grade disease. Significant clinical predictors of upgrading to higher patterns include PSA and P+, which identify a very high-risk class that needs repeat biopsies in order to reclassify tumor grade.

Objective: To investigate the effects of prostate cancer (PCa) surgery on the stress system and to identify potential independent factors associating with stress recovery. Methods: The design of the study was prospective and PCa surgery included robot assisted radical prostatectomy (RARP) or retropubic radical prostatectomy (RRP). Between February 2013 to December 2014, 315 consecutive patients were evaluated. The effects of PCa surgery on the stress system were measured by cortisol serum levels before and after surgery on postoperative day (POD) 0, 1, 3, 5 and 45. Cortisol variations in the population and subpopulation (RARP vs. RRP) of patients were investigated by statistical methods. Factors associating with stress recovery were assessed by simple linear regression (SLR) and multiple linear regression (MLR) analysis. Results: RARP was performed in 75.9% of cases. In the patient population, there were wide serum cortisol perioperative variations. PCa surgery triggered the stress system which immediately (POD 0) responded by cortisol overproduction which induced the negative feedback mechanism that started on POD 1, continued on POD 3, was still ongoing on POD 5 and completely settled on POD 45 (stress recovery). In the subpopulation of patients, significantly lower cortisol serum levels were detected on POD 3–5 in RARP cases in whom cortisol levels were close to preoperative levels (stress recovery) on POD 5. Independent predictive factors of serum cortisol on POD 5 (stress recovery) were preoperative cortisol (p = 0.02), cortisol levels on POD 3 (p