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Purpose: We sought to investigate predictors of unfavorable tumor upgrading in very favorable intermediate-risk (IR) prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy, in addition to evaluate how it may affect the risk of disease progression., Methods: A very favorable subset of IR PCa patients presenting with prostate-specific antigen (PSA) < 10 ng/mL, percentage of biopsy positive cores (BPC) < 50%, and either International Society of Urological Pathology (ISUP) grade group 1 and clinical stage T2b or ISUP grade group 2 and clinical stage T1c-2b was identified. Unfavorable pathology at radical prostatectomy was defined as the presence of ISUP grade group > 2 (unfavorable tumor upgrading), extracapsular extension (ECE), and seminal vesicle invasion (SVI). Disease progression was defined as the event of biochemical recurrence and/or local recurrence and/or distant metastases. Associations were evaluated by Cox regression and logistic regression analyses., Results: Overall, 210 patients were identified between January 2013 and October 2020. Unfavorable tumor upgrading was detected in 71 (33.8%) cases, and adverse tumor stage, including ECE or SVI in 18 (8.6%) and 11 (5.2%) patients, respectively. Median (interquartile range) follow-up was 38.5 (16-61) months. PCa progression occurred in 24 (11.4%) patients. Very favorable IR PCa patients with unfavorable tumor upgrading at final pathology showed a persistent risk of disease progression, which hold significance after adjustment for all factors (Hazard Ratio [HR]: 5.95, 95% Confidence Interval [CI]: 1.97-17.92, p = 0.002) of which PSA was an independent predictor (HR: 1.52, 95% CI 1.12-2.08, p = 0.008). Moreover, these subjects were more likely to belong to the biopsy ISUP grade group 2., Conclusions: Very favorable IR PCa patients hiding unfavorable tumor upgrading were more likely to experience disease progression. Unfavorable tumor upgrading involved about one-third of cases and was less likely to occur in patients presenting with biopsy ISUP grade group 1. Tumor misclassification is an issue to discuss, when counseling this subset of patients for active surveillance because of the risk of delayed active treatment., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: To investigate the potential prognostic impact of Briganti's 2012 nomogram in EAU intermediate-risk patients presenting with an unfavorable tumor grade and treated with robot-assisted radical prostatectomy, eventually associated with extended pelvic lymph node dissection., Materials and Methods: From January 2013 to December 2021, the study included 179 EAU intermediate-risk patients presenting with an unfavorable tumor grade (ISUP 3), eventually associated with a PSA of 10-20 ng/ml and/or cT-2b. Briganti's 2012 nomogram was assessed as both a continuous and dichotomous variable, categorized according to the median (risk score ⩾7% vs <7%). Disease progression, defined as biochemical recurrence and/or metastatic progression, was evaluated using Cox proportional hazards in both univariate and multivariate analyses., Results: Disease progression occurred in 43 (24%) patients after a median (95% CI) follow-up of 78 (65.7-88.4) months. The nomogram risk score predicted disease progression, evaluated both as a continuous variable (hazard ratio, HR = 1.064; 95% CI: 1.035-1.093; p  < 0.0001) and as a categorical variable (HR = 3.399; 95% CI: 1.740-6.638; p  < 0.0001). This association was confirmed in multivariate analysis, where hazard ratios remained consistent even after adjusting for clinical and pathological factors., Conclusions: In EAU intermediate-risk PCa cases presenting with an unfavorable tumor grade and treated surgically, Briganti's 2012 nomogram was associated with disease progression after surgery. Consequently, as the nomogram risk score increased, patients were more likely to experience PCa progression, facilitating the stratification of the patient population into distinct prognostic subgroups., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: We assessed the prognostic impact of the 2012 Briganti nomogram on prostate cancer (PCa) progression in intermediate-risk (IR) patients presenting with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b treated with robot assisted radical prostatectomy eventually associated with extended pelvic lymph node dissection., Materials and Methods: From January 2013 to December 2021, data of surgically treated IR PCa patients were retrospectively evaluated. Only patients presenting with the above-mentioned features were considered. The 2012 Briganti nomogram was assessed either as a continuous and a categorical variable (up to the median, which was detected as 6%, vs. above the median). The association with PCa progression, defined as biochemical recurrence, and/or metastatic progression, was evaluated by Cox proportional hazard regression models., Results: Overall, 147 patients were included. Compared to subjects with a nomogram score up to 6%, those presenting with a score above 6% were more likely to be younger, had larger/palpable tumors, presented with higher PSA, underwent tumor upgrading, harbored non-organ confined disease, and had positive surgical margins at final pathology. PCa progression, which occurred in 32 (21.7%) cases, was independently predicted by the 2012 Briganti nomogram both considered as a continuous (Hazard Ratio [HR]:1.04, 95% Confidence Interval [CI]:1.01-1.08;p=0.021), and a categorical variable (HR:2.32; 95%CI:1.11-4.87;p=0.026), even after adjustment for tumor upgrading., Conclusions: In IR PCa patients with PSA <10ng/mL, ISUP grade group 3, and clinical stage up to cT2b, the 2012 Briganti nomogram independently predicts PCa progression. In this challenging subset of patients, this tool can identify prognostic subgroups, independently by upgrading issues., Competing Interests: None declared., (Copyright® by the International Brazilian Journal of Urology.)

Background: The aim is to evaluate factors impacting operating time (OT) during robot-assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND) for prostate cancer., Methods: Overall, 1289 patients underwent RARP from January 2013 to December 2021. ePLND was performed in 825 cases. Factors potentially associated with OT variations were assessed. Three low-volume (LVS) and two high-volume surgeons (HVS) performed the procedures. A linear regression model was computed to assess associations with OT variations., Results: When RARP was performed by HVS an OT decrease was observed independently by significant clinical (Body Mass Index [BMI]; prostate volume [PV]) and anatomical/perioperative features (prostate weight [PW]; intraoperative blood loss [BL]) both in clinical (change in OT: -42.979 minutes; 95% CI: -51.789; -34.169; P<0.0001) and anatomical/perioperative models (change in OT: -40.020 minutes; 95% CI: -48.494; -31.587; P<0.0001). A decreased OT was observed in clinical (change in OT: -27.656 minutes; 95% CI: -33.449; -21.864; P<0.0001) and anatomical/perioperative (change in OT: -24.935 minutes; 95% CI: -30.562; -19.308; P<0.0001) models also in case of RARP with ePLND performed by HVS, independently by BMI, PV, PSA as well as for PW, seminal vesicle invasion, positive surgical margins, and BL., Conclusions: In a tertiary academic referral center, OT decreased when RARP was performed by HVS, independently of adverse clinical and anatomical/perioperative factors. Available OT loads can be planned to optimize waiting lists, teaching tasks, operative costs, and surgeon's volume.

To evaluate the prognostic potential of the 2012 Briganti nomogram for pelvic lymph node invasion on disease progression after surgery in intermediate-risk (IR) prostate cancer (PCa) patients with favorable tumor grade (International Society of Urological Pathology grade group 1 or 2), eventually associated with adverse clinical features as PSA between 10 and 20 ng/mL and/or clinical stage T2b. All IR PCa patients treated with robot-assisted radical prostatectomy and eventually extended pelvic lymph node dissection at the Department of Urology of the Integrated University Hospital of Verona between 2013 and 2021, with the abovementioned features, and available follow-up were considered. The 2012 Briganti nomogram score was assessed both as a continuous and dichotomous variable, where a mean risk score of 4% was used a threshold. The independent predictor status of the nomogram score on disease progression defined as the occurrence of biochemical recurrence and/or metastatic progression was evaluated using the Cox regression analysis. Overall, 348 patients were enrolled in the study. Median (interquartile range) follow-up was 98 (83.5-112.4) months. At multivariable Cox regression analysis, PCa progression, which occurred in 65 (18.7%) cases, was independently predicted only by the 2012 Briganti nomogram score evaluated as a continuous variable, among all considered clinical features (HR 1.16; 95%CI 1.08-1.24; p < 0.001). In addition, patients presenting with a nomogram score ≥ 4% were more likely to experience disease progression even after adjustment for clinical (HR 2.22, 95%CI 1.02-4.79; p = 0.043) and pathological (HR 1.80; 95%CI 1.06-3.05; p = 0.031) factors. In the examined patient population, the 2012 Briganti nomogram predicted PCa progression after surgery. Accordingly, as the risk score increased, patients were more likely to progress, independently by the occurrence of adverse pathology in the surgical specimen. The 2012 Briganti nomogram score categorized according to the mean value allowed to identify prognostic subgroups., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objective: To evaluate the influence of endogenous testosterone density (ETD) and tumor load density (TLD) in the surgical specimen of prostate cancer (PCa) patients., Methods: ETD was assessed as the ratio of endogenous testosterone (ET) to prostate volume (PV). TLD was calculated as the ratio of tumor load (TL) to prostate weight. Preoperative prostate-specific antigen relative densities (PSAD) and percentage of biopsy-positive cores (BPCD) were also assessed. The association of high TLD (above the first quartile) with clinical and pathological factors was assessed by the logistic regression model (univariate and multivariate analysis)., Results: Between November 2014 and December 2019, ET was measured in 805 cases treated with radical prostatectomy (RP). Median (IQR) of ET and ETD was 412 (321.4-519 ng/dL) and 9.8 (6.8-14.4 ng/(dLxmL)) as well as for TL and TLD was 20 (10-30%) and 0.33 (0.17-0.58%/gr), respectively. As a result, high TLD was detected in 75% of cases. A positive independent association was found between high TLD and ETD. Accordingly, as ETD levels increased, the risk of detecting high TLD in the surgical specimen increased, regardless of PSAD and BPCD., Conclusions: At diagnosis of PCa, a positive independent association was found between ETD and risk of high TLD. Subjects with increasing ETD levels were more likely to have high TLD, associated with unfavorable pathology features. The positive association between ETD and TLD in the prostate microenvironment might adversely influence PCa's natural history., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Routine processing of prostate biopsies requires conventional steps that usually take a few days. The aim of this study was to validate the use of fluorescence laser confocal microscopy (FCM) for real-time diagnostics., Methods: We prospectively tested images from prostate needle biopsies (75 images were evaluated by FCM and conventional slides). Two pathologists reviewed the images and assessed agreements between FCM versus conventional slides and between pathologists (κ-values). Interpretation was performed on digital images from the VivaScope 2500 confocal microscope (MAVIG GmbH, Munich, Germany; Caliber I.D., Rochester, NY, USA) placed in the urological operating room. Cancerous versus benign tissue was the primary focus, then the application of the grading system., Results: Cancer was diagnosed in 24 conventional slides (on 75 images) in which agreement among pathologists was high for both conventional (κ=0.96) and FMC (κ=0.84). 1/24 (4%) was ISUP/WHO grade group I, 12/24 (50%) II, 8/24 (33%) III, 2/24 (8%) IV and 1/24 (4%) grade V. Near perfect agreement was obtained for grades I, IV and V (κ=0.85). Grade III values achieved a moderate agreement (κ=0.55). The mean time for laser scanning was 9 minutes. For the remaining non-tumor images, agreement was nearly perfect (κ=0.81)., Conclusions: We validated the use of FCM for real-time cancer detection in prostate biopsies.

Objective: This study aimed to evaluate the impact of palpable prostate tumors on digital rectal exam (DRE) on the disease progression of prostate cancer (PCa) treated with RARP surgery in a tertiary referral center., Materials and Methods: Overall, 901 patients were evaluated in a period ranging from January 2013 to October 2020. In the surgical specimen, unfavorable pathology included ISUP grade group ≥3, seminal vesicle invasion (SVI), and pelvic lymph node invasion (PLNI). Disease progression was defined as the occurrence of biochemical recurrence and/or local recurrence and/or distant metastases; its association with the primary endpoint was evaluated by Cox's proportional model., Results: Palpable prostate tumors were detected in 359 (39.8%) patients. The overall median (IQR) follow-up was 40 months (17-59). PCa progressed in 159 cases (17.6%). Nodularity or induration of the prostate at DRE was significantly associated with features of unfavorable pathology, increased risk of PCa progression (hazard ratio, HR = 1.902; 95% CI: 1.389-2.605; p < 0.0001) and, on multivariable analysis, was an independent prognostic factor for disease progression after adjusting for clinical and pathological variables., Conclusions: Prostate tumors presenting with an abnormal DRE finding have an independent adverse outcome for disease progression after PCa surgery. They provide also independent prognostic information, as they may be more aggressive than impalpable PCa., (© 2023. The Author(s).)

Objectives: This study aimed to assess more clinical and pathological factors associated with prostate cancer (PCa) progression in high-risk PCa patients treated primarily with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND) in a tertiary referral center., Materials and Methods: In a period ranging from January 2013 to October 2020, RARP and ePLND were performed on 180 high-risk patients at Azienda Ospedaliera Universitaria Integrata of Verona (Italy). PCa progression was defined as biochemical recurrence/persistence and/or local recurrence and/or distant metastases. Statistical methods evaluated study endpoints, including Cox's proportional hazards, Kaplan-Meyer survival curves, and binomial logistic regression models., Results: The median age of included patients was 66.5 [62-71] years. Disease progression occurred in 55 patients (30.6%), who were more likely to have advanced age, palpable tumors, and unfavorable pathologic features, including high tumor grade, stage, and pelvic lymph node invasion (PLNI). On multivariate analysis, PCa progression was predicted by advanced age (≥ 70 years) (HR = 2.183; 95% CI = 1.089-4377, p = 0.028), palpable tumors (HR = 3.113; 95% CI = 1.499-6.465), p = 0.002), and PLNI (HR = 2.945; 95% CI = 1.441-6.018, p = 0.003), which were associated with clinical standard factors defining high-risk PCa. Age had a negative prognostic impact on elderly patients, who were less likely to have palpable tumors but more likely to have high-grade tumors., Conclusions: High-risk PCa progression was independently predicted by advanced age, palpable tumors, and PLNI, which is associated with standard clinical prognostic factors. Consequently, with increasing age, the prognosis is worse in elderly patients, who represent an unfavorable age group that needs extensive counseling for appropriate and personalized management decisions., (© 2023. The Author(s).)

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., (Copyright © 2023 Copyright: © The Author(s)(2023).)

Purpose: To test the role of endogenous total testosterone (ETT) as a predictor of prostate cancer (PCa) progression in patients treated with robot assisted radical prostatectomy for clinically localized disease., Methods: Between November 2014 and December 2019, 580 consecutive patients were evaluated. Preoperative ETT levels were classified as ≤ 350 ng/dL vs. > 350 ng/dL. The associations between ETT levels and the risk of PCa progression, defined as any event of biochemical recurrence and/or local recurrence and/or distant metastases, or other clinical and pathological factors were evaluated by regression analyses., Results: Preoperative ETT levels resulted ≤ 350 ng/dL in 173 (29.8%) patients. Disease progression occurred in 101 (17.1%) cases. Progressing patients were more likely to present with PSA levels > 10 ng/mL, as well as with unfavorable tumor grade (ISUP 4-5) and stage (pT3b) at final pathology, but less likely to have ETT levels ≤ 350 ng/mL. On clinical multivariable Cox regression models, ETT ≤ 350 ng/mL exhibited a statistically significant protective effect on tumor progression (hazard ratio: 0.57, p = 0.013). Subjects presenting with ETT levels ≤ 350 ng/mL were less likely to harbor ISUP 4-5 tumor grade either at biopsy (odds ratio [OR]: 0.46, p = 0.028) or final pathology (OR: 0.45, p = 0.032)., Conclusions: At PCa diagnosis, ETT, which associates with ISUP tumor grade, is an independent predictor of disease progression. Accordingly, as ETT decreases to levels ≤ 350 ng/dL, the risk of unfavorable tumor grade decreases, and a more favorable prognosis is expected. Preoperative ETT levels may allow further patient stratification along prognostic risk groups., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

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., (© 2022. The Author(s).)

Background: The investigate the associations of the ASA physical status system with clinical, pathological, and perioperative features of prostate cancer (PCa) patients treated with radical prostatectomy (RP) that eventually associated with pelvic lymph node dissection (PLND)., Methods: We performed a retrospective analysis of prospective collected data from January 2013 to October 2020, including1329 patients. The ASA system was preoperatively assessed for each patient. Evaluated clinical factors were grouped as preoperative, perioperative, and pathological and were statistically associated with the ASA system. Continuous variables were represented as medians with relative interquartile ranges (IQR) and categorical factors were assessed as frequencies (percentages). Associations and risk of each ASA Class with population features were assessed by the multinomial logistic regression model (univariate and multivariate analysis). All tests were two-sided with P<0.05 considered to indicate statistical significance., Results: Postoperative complications at discharge occurred in 27.2%. The distribution of the ASA physical status system was as follows: ASA I 108 patients (8.1%), ASA II 1081 subjects (81.3%) and ASA III 140 cases (10.5%). Median length of hospital state (LOHS) was the same for ASA groups I and II (4 days), but longer (5 days) for the ASA group III. On MVA, the risk of delayed hospital stay was associated only with ASA III patients and was independent from age and BMI. Clavien-Dindo complications greater than 2 did not show any independent association with the ASA system., Conclusions: The ASA preoperative physical status system predicted the likelihood of longer LOHS.

Introduction and Objective: Although advanced age doesn't seem to impair oncological outcomes after robot-assisted radical prostatectomy (RARP), elderly patients have increased rates of prostate cancer (PCa) related deaths due to a higher incidence of high-risk disease. The potential unfavorable impact of advanced age on oncological outcomes following RARP remains an unsettled issue. We aimed to evaluate the oncological outcome of PCa patients > 69 years old in a single tertiary center., Materials and Methods: 1143 patients with clinically localized PCa underwent RARP from January 2013 to October 2020. Analysis was performed on 901 patients with available follow-up. Patients ≥ 70 years old were considered elderly. Unfavorable pathology included ISUP grade group > 2, seminal vesicle, and pelvic lymph node invasion. Disease progression was defined as biochemical and/or local recurrence and/or distant metastases., Results: 243 cases (27%) were classified as elderly patients (median age 72 years). Median (IQR) follow-up was 40.4 (38.7-42.2) months. Disease progression occurred in 159 cases (17.6%). Elderly patients were more likely to belong to EAU high-risk class, have unfavorable pathology, and experience disease progression after surgery (HR = 5.300; 95% CI 1.844-15.237; p = 0.002) compared to the younger patients., Conclusions: Elderly patients eligible for RARP are more likely to belong to the EAU high-risk category and to have unfavorable pathology that are independent predictors of disease progression. Advanced age adversely impacts on oncological outcomes when evaluated inside these unfavorable categories. Accordingly, elderly patients belonging to the EAU high-risk should be counseled about the increased risk of disease progression after surgery., (© 2022. The Author(s).)

To test the hypothesis of associations between the ABO blood group system (ABO-bg) and prostate cancer (PCa) features in the surgical specimen of patients treated with robot-assisted radical prostatectomy (RARP). Between January 2013 and October 2020, 1114 patients were treated with RARP. Associations of ABO-bg with specimen pathological features were evaluated by statistical methods. Overall, 305 patients were low risk (27.4%), 590 intermediate risk (50%) and 219 high risk (19.6%). Pelvic lymph node dissection was performed in 678 subjects (60.9%) of whom 79 (11.7%) had cancer invasion. In the surgical specimen, tumor extended beyond the capsule in 9.8% and invaded seminal vesicles in 11.8% of cases. Positive surgical margins (PSM) were detected in 271 cases (24.3%). The most frequently detected blood groups were A and O, which were equally distributed for both including 467 patients (41.9%), followed by groups B (127 cases; 11.4%) and AB (53 subjects; 4.8%). Among specimen factors, the ABO-bgs associated only with the risk of PSM, which was higher for blood group O (30.4%) compared with group A (19.5%) after adjusting for other standard clinical predictors (odds ratio, OR = 1.842; 95% CI 1.352-2.509; p < 0.0001). Along the ABO-bgs, the risk of PSM was increased by group O independently by other standard preoperative factors. The ABO-bgs may represent a further physical factor for clinical assessment of PCa patients, but confirmatory studies are required., (© 2021. The Author(s).)

To evaluate potential factors associated with the risk of perioperative blood transfusion (PBT) with implications on length of hospital stay (LOHS) and major post-operative complications in patients who underwent robot-assisted radical prostatectomy (RARP) as a primary treatment for prostate cancer (PCa). In a period ranging from January 2013 to August 2019, 980 consecutive patients who underwent RARP were retrospectively evaluated. Clinical factors such as intraoperative blood loss were evaluated. The association of factors with the risk of PBT was investigated by statistical methods. Overall, PBT was necessary in 39 patients (4%) in whom four were intraoperatively. Positive surgical margins, operating time and intraoperative blood loss were associated with perioperative blood transfusion on univariate analysis. On multivariate analysis, the risk of PBT was predicted by intraoperative blood loss (odds ratio, OR 1.002; 95% CI 1.001-1.002; p < 0.0001), which was associated with prolonged operating time and elevated body mass index (BMI). PBT was associated with delayed LOHS and Clavien-Dindo complications > 2. In patients undergoing RARP as a primary treatment for PCa, the risk of PBT represented a rare event that was predicted by severe intraoperative bleeding, which was associated with increased BMI as well as with prolonged operating time. In patients who received a PBT, prolonged LOHS as well as an elevated risk of major Clavien-Dindo complications were seen., (© 2021. The Author(s).)

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., (© 2022. The Author(s).)

To investigate factors associated with the risk of major complications after radical prostatectomy (RP) by the open (ORP) or robot-assisted (RARP) approach for prostate cancer (PCa) in a tertiary referral center. 1062 consecutive patients submitted to RP were prospectively collected. The following outcomes were addressed: (1) overall postoperative complications: subjects with Clavien-Dindo System (CD) one through five versus cases without any complication; (2) moderate to major postoperative complications: cases with CD < 2 vs.  ≥ 2, and 3) major post-operative complications: subjects with CDS CD ≥  3 vs.  < 3. The association of pre-operative and intra-operative factors with the risk of postoperative complications was assessed by the logistic regression model. Overall, complications occurred in 310 out of 1062 subjects (29.2%). Major complications occurred in 58 cases (5.5%). On multivariate analysis, major complications were predicted by PCa surgery and intraoperative estimated blood loss (EBL). ORP compared to RARP increased the risk of major CD complications from 2.8 to 19.3% (OR = 8283; p < 0.0001). Performing ePLND increased the risk of major complications from 2.4 to 7.4% (OR = 3090; p < 0.0001). Assessing intraoperative blood loss, the risk of major postoperative complications was increased by BL above the third quartile when compared to subjects with intraoperative blood loss up to the third quartile (10.2% vs. 4.6%; OR = 2239; 95%CI: 1233-4064). In the present cohort, radical prostatectomy showed major postoperative complications that were independently predicted by the open approach, extended lymph-node dissection, and excessive intraoperative blood loss., (© 2021. The Author(s).)

Objective: The aim of this study is to evaluate the influence of endogenous testosterone density (ETD) on features of aggressive prostate cancer (PCa) in intermediate-risk disease treated with radical prostatectomy and extended pelvic lymph node dissection., Materials and Methods: Density measurements included the ratio of endogenous testosterone (ET), prostate-specific antigen (PSA), and percentage of biopsy positive cores (BPC) on prostate volume (ETD, PSAD, and BPCD, respectively). The ratio of percentage of cancer invading the gland (tumor load, TL) on prostate weight (TLD) was also calculated. Unfavorable disease (UD) was defined as tumor upgrading (ISUP >3) and/or upstaging (pT >2) and/or lymph node invasion (LNI). Associations of ETD with features of aggressive PCa, including UD and TLD, were evaluated by logistic and linear regression models., Results: Evaluated cases were 338. Subjects with upgrading, upstaging, and LNI were 61/338 (18%), 73/338 (21%), and 25/338 (7.4%), respectively. TLD correlated with UD (Pearson's correlation coefficient, r = 0.204; p < 0.0001), PSAD (r = 0.342; p < 0.0001), BPCD (r = 0.364; p < 0.0001), and ETD (r = 0.214; p < 0.0001), which also correlated with BMI (r = -0.223; p < 0.0001), PSAD (r = 0.391; p < 0.0001), and BPCD (r = 0.407; p < 0.0001). TLD was the strongest independent predictor of UD (OR = 2.244; 95% CI = 1.146-4.395; p = 0.018). In the multivariate linear regression model predicting BPCD, ETD was an independent predictor (linear regression coefficient, b = 0.026; 95% CI: 0.016-0.036; p < 0.0001) together with PSAD (b = 1.599; 95% CI: 0.863-2.334; p < 0.0001) and TLD (b = 0.489; 95% CI: 0.274-0.706; p < 0.0001). According to models, TLD increased as ETD increased accordingly, but mean ET levels were significantly lower for patients with UD., Conclusions: As ETD measurements incremented, the risk of large tumors extending beyond the prostate increased accordingly, and patients with lower ET levels were more likely to occult UD. The influence of ETD on PCa biology should be addressed by prospective studies., (© 2022 S. Karger AG, Basel.)

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 < 0.0001), ETD (b = 0.032; 95% CI 0.023-0.040; p < 0.0001) and TL (b = 0.009; 95% CI 0.005-0.014; p < 0.0001). As BPCD increased, ETD and ET levels increased accordingly, but patients with BPCD > 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., (© 2021. The Author(s).)

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 < 0.0001), PSAD (b = 1.962; 95% CI 1.067-2.586; p < 0.0001) and tumor upgrading (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., (© 2021. The Author(s).)

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., (© 2021. The Author(s).)

Background: The aim of this study is to evaluate the incidence and risk factors of incidental prostate cancer (IPCA) in a contemporary cohort of lower urinary tract symptoms (LUTS) patients who underwent trans-urethral resection of the prostate (TURP)., Methods: A series of 458 consecutive patients who underwent TURP were evaluated between January 2016 to June 2018. Evaluated factors included age (years), Body Mass Index (BMI; kg/square meters), treatment with inhibitors of 5-alpha reductase, previous prostate biopsies, basal prostate specific antigen (PSA) levels (ng/mL), serum leukocyte count (×10 9 /L), weight of resected prostate tissue (grams), grade and stage of IPCA. The multivariate logistic regression model evaluated associations of significant clinical factors with the risk of IPCA., Results: Overall, IPCA was detected in 30 of 454 patients (6.6%). A mean of 21.8 g of tissue was resected. The mean number of positive chips was 5.6 (mean percentage 3.9%) with tumor grade group 1 in 22 cases (73.4%) and tumor stage cT1a in 23 patients (76.7%). On multivariate analysis, independent factors that were positively associated with the risk of IPCA were BMI (odds ratio, OR=1.121; P=0.017) and leukocyte count (OR=1.144; P=0.027)., Conclusions: In a contemporary cohort of patients undergoing TURP for the treatment of LUTS, the risk of IPCA was not negligible with a rate of being 6.6%. BMI and serum leukocyte count were found to be independent factors that were positively associated with the risk of IPCA.

Objective: To investigate by means of a randomized clinical trial the safety of no drain in the pelvic cavity after robot-assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND). Materials and Methods: From May to December 2016, 112 consecutive patients who underwent RARP with or without ePLND were prospectively randomized into a control group (CG) and study group (SG). In the CG, a drain was placed in the pelvic cavity at the end of surgery and removed after 24 hours. The trial was designed to assess noninferiority. The primary endpoint was evaluated as complication rates graded by the Clavien-Dindo score (CDS). Secondary endpoints included length of hospital stay (LOHS) and hospital readmission (RAD). Results and Limitations: At final analysis, 56 patients were in the CG and 54 belonged to the SG. The groups were homogenous for all preoperative and perioperative variables and did not show any difference in CDS complication rates (28.9% in the CG and 20.4% in the SG; p  = 0.254), LOHS (on average 4 days in each group; p  = 0.689), and RAD rates (3.6% in the CG and 3.7% in the SG; p  = 0.970). Conclusions: In a modern cohort of patients who underwent RARP with or without ePLND, a single-center randomized controlled trial showed that no-drain policy is equivalent to drain after RARP in terms of CDS complication rate, LOHS, and RAD rate. The option of placing a postoperative drain for the first 24 hours could be considered in cases of difficult urethrovesical anastomosis with uncertain watertightness.

Objective: To investigate the associations of endogenous testosterone with prostate growing disorders (PGD) including benign prostatic hyperplasia (BPH) and prostate cancer (PCA)., Methods: 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., Results: 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 < 0,0001) and prostate volume (OR = 0.930; 95% CI 0.919-0.940; p < 0.0001) but increased by PSA (OR = 1.652; 95% CI 1.542-1.769; p < 0.0001). On multivariate linear regression analysis, endogenous testosterone inversely associated with body mass index (BMI) (regression coefficient, b =  - 0.279; p = 0.002) and PCA (b =  - 2.935; p < 0.0001)., Conclusions: In the aging male, endogenous testosterone independently predicted malignant prostate disorders, which associated with decreased hormone levels along BMI categories. Endogenous testosterone is a further marker for evaluating prostate growing disorders in clinical practice; however, controlled studies are required.

Objective: Prostate cancer (PCa) is the second most common malignancy in men. Radiotherapy and surgery successfully control organ-confined tumors, although, locally advanced/high-risk PCa frequently progress to the metastatic stage of the disease, which is uncurable. Identification of novel strategies to improve the efficacy of standard clinical protocols is a primary need. Among the molecular targets of potential clinical interest recently highlighted by accurate preclinical studies, the TRPM8 cation channel is particularly promising. In this study, we aim at establishing a standardized immunohistochemistry protocol to evaluate TRPM8 expression in normal and pathological prostate tissues., Methods: The specificity and sensitivity of TRPM8 antibody ACC-049 was validated in different human prostate cell lines by western blot and immunocytochemistry analyses. Expression of the TRPM8 channel in normal and pathological prostate tissue was evaluated by immunohistochemistry using a tissue microarray containing 58 cases of prostate adenocarcinomas and in primary and lymph nodes metastatic human PCa matched specimens., Results: TRPM8 expression marks luminal epithelial cells in benign prostate tissue. In malignant lesions of the prostate, TRPM8 expression is frequently more abundant in advanced stages of the disease (PCa stage III/IV). Finally, lymph node metastases and matched primary tumors show similar amounts of the channel., Conclusions: Collectively, our results reinforce the importance of TRPM8 as prostate biomarker and emphasize the value of the channel as promising novel molecular target for the treatment of prostate adenocarcinoma., (Copyright © 2021 Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.)

Objective: In patients with intermediate- and high-risk localized prostate cancer (PCa), improving the detection of occult lymph node metastases could play a pivotal role for therapeutic counseling and planning. The recent literature shows that several clinical factors may be related to PCa aggressiveness. The aim of this study is to investigate the potential associations between clinical factors and the risk of multiple lymph node invasion (LNI) in patients with intermediate- and high-risk localized PCa (cT1/2, cN0, and ISUP grading group >2 and/or prostate-specific antigen (PSA) >10 ng/mL) who underwent radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND)., Materials and Methods: In a period ranging from January 2014 to December 2018, 880 consecutive patients underwent RP with ePLND for PCa. Among these, 481 met the inclusion criteria and were selected. Data were prospectively collected within an institutional dataset and retrospectively analyzed. Age (years), body mass index (BMI; kg/m2), PSA (ng/mL), prostate volume (mL), and biopsy positive cores (BPC; %) were recorded for each case. BMI and BPC were considered continuous and categorical variables, respectively. The logistic regression models evaluated the association of clinical factors with the risk of nodal metastases., Results: LNI was detected in 73/418 patients (15.2%) of whom 40/418 (8.3%) harbored multiple LNI (median 2, IQR: 3-4). On multivariate analysis, BMI was independently associated with the risk of multiple LNI in the pathological specimen when compared with patients without LNI (OR = 1.147; p = 0.018), as well as the percentage of biopsy positive cores (OR = 1.028; p < 0.0001) and European Association of Urology high-risk class (OR = 5.486; p < 0.0001). BMI was the only predictor of multiple LNI when compared with patients with 1 positive node (OR = 1.189, p = 0.027)., Conclusions: In intermediate- and high-risk localized PCa, BMI was an independent predictor of the risk of multiple lymph node metastases. The inclusion of BMI within LNI risk calculators could be helpful, and a detailed counseling in obese patients should be required., (© 2020 S. Karger AG, Basel.)

Objective: The aim of the study was to test the hypothesis that endogenous total testosterone (TT) may relate to incidental prostate cancer (iPCA) in patients with lower urinary tract symptoms (LUTS) associated with prostate enlargement undergoing transurethral resection of the prostate (TURP)., Methods: The hypothesis was tested in contemporary cohort of patients who underwent TURP because of LUTS due to prostate enlargement after excluding the suspect of PCA. In period running from January 2017 to November 2019, 389 subjects were evaluated. Endogenous testosterone was measured preoperatively between 8:00 and 10:00 o'clock in the morning. Relationships between TT and iPCA were evaluated by statistical methods., Results: Overall, iPCA was detected in 18 cases (4.6%) with clinical stage cT1a or International Society of Urologic Pathology (ISUP) < 2 in 11 patients (61.1%). Endogenous testosterone was inversely associated with age and BMI in the study population but not in the subgroup with iPCA in wholly endogenous TT strongly correlated to both number of chips involved by cancer (Pearson's correlation coefficient, r = 0.553; p = 0.017) and ISUP > 2 (r = 0.504; p = 0.033). The positive association of endogenous TT with both tumor load and tumor grade was confirmed by the linear regression model with high-regression coefficients for the former (regression coefficient, b = 0.307; 95% confidence interval, 95% CI: 0.062-0.551; and p = 0.017) as for the latter (b = 5.898; 95% CI: 0.546-11.249; and p = 0.033)., Conclusions: Preoperative endogenous TT is associated with features of iPCA. The influence of iPCA on endogenous testosterone needs to be addressed by a large multicenter prospective trial., (© 2021 S. Karger AG, Basel.)

Therapy resistance is a major roadblock in oncology. Exacerbation of molecular dysfunctions typical of cancer cells have proven effective in twisting oncogenic mechanisms to lethal conditions, thus offering new therapeutic avenues for cancer treatment. Here, we demonstrate that selective agonists of Transient Receptor Potential cation channel subfamily M member 8 (TRPM8), a cation channel characteristic of the prostate epithelium frequently overexpressed in advanced stage III/IV prostate cancers (PCa), sensitize therapy refractory models of PCa to radio, chemo or hormonal treatment. Overall, our study demonstrates that pharmacological-induced Ca 2+ cytotoxicity is an actionable strategy to sensitize cancer cells to standard therapies.

Objective: To evaluate the factors associated with the risk of hospital readmission after robot assisted radical prostatectomy (RARP) with or without extended pelvic lymph node dissection (ePLND) for prostate cancer (PCA) over a long term., Materials and Methods: The risk of readmission was evaluated by clinical, pathological, and perioperative factors. Skilled and experienced surgeons performed the procedures. Patients were followed for complications and hospital readmission for a period of six months. The logistic regression model and Cox's proportional hazards assessed the association of factors with the risk of readmission., Results: From January 2013 to December 2018, 890 patients underwent RARP; ePLND was performed in 495 of these patients. Hospital readmission was detected in 25 cases (2.8%); moreover, it was more frequent when RARP was performed with ePLND (4.4% of cases) than without (0.8% of patients). On the final multivariate model, ePLND was the only independent factor that was positively associated with the risk of hospital readmission (hazard ratio, HR = 5935; 95%CI 1777-19,831; p = 0.004)., Conclusions: Over the long term after RARP for PCA, the risk of hospital readmission is associated with ePLND. In patients who underwent RARP and ePLND, 4.4% of them had a readmission, compared to RARP alone, in which only 0.8% of cases had a readmission. When ePLND is planned for staging pelvic lymph nodes, patients should be informed of the increased risk of hospital readmission.

Objective: 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)., Materials and Methods: 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., Results: 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 < 0.0001). Among metastatic patients, BMI ≥ 30 was the only factor associated with the risk of multiple LNI (OR = 5.250; p = 0.041)., Conclusions: In patients with clinically localized EAU intermediate and high-risk classes PCa who underwent RARP and ePLND, obesity was a risk factor of multiple LNI.

The objective of this study is to evaluate if surgeon volume and stratifying positive surgical margins (PSM) into focal and non-focal may differentially impact the risk of biochemical recurrence (BCR) after robot-assisted radical prostatectomy (RARP). Between January 2013 and December 2017, 732 consecutive patients were evaluated. The population included negative cases (control group) and PSM subjects (study group). PSMs were stratified as focal (≤ 1 mm) or non-focal (> 1 mm). A logistic regression model assessed the independent association of factors with the risk of PSM. The risk of BCR of PSM and other factors was assessed by Cox's multivariate proportional hazards. Overall, 192 (26.3%) patients had PSM focal in 133 patients; non-focal in 59 cases. Focal PSM was associated with the percentage of biopsy positive cores (BPC; OR 1.011; p = 0.015), extra-capsular extension (pT3a stage; OR 2.064; p = 0.016), seminal vesicle invasion (pT3b; OR 2.150; p = 0.010), body mass index (odds ratio, OR 0.914; p = 0.006), and high surgeon volume (OR 0.574; p = 0.006). BPC (OR 1.013; p = 0.044), pT3a (OR 4.832; p < 0.0001) and pT3b stage (OR 5.153; p = 0.001) were independent predictors of the risk of non-focal PSM. Surgeon volume was not a predictor of non-focal PSM (p = 0.224). Independent factors associated with the risk of BCR were baseline PSA (hazard ratio, HR 1.064; p = 0.004), BPC (HR 1.015; p = 0.027), ISUP biopsy grade group (BGG) 2/3 (HR 2.966; p 0.003) and BGG 4/5 (HR 3.122; p = 0.022) pathologic grade group 4/5 (HR 3.257; p = 0.001), pT3b (HR 2.900; p = 0.003), and non-focal PSM (HR 2.287; p = 0.012). Surgeon volume was not a predictor of BCR (p = 0.253). High surgeon volume is an independent factor that lowers the risk of focal PSM. Surgeon volume does not affect non-focal PSM and BCR. Negative as well as focal PSM are not associated with BCR.

Objective: 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)., Methods: 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., Results: 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., Conclusions: 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.

Our aim is to evaluate the association between body mass index (BMI) and preoperative total testosterone (TT) levels with the risk of single and multiple metastatic lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy and extended pelvic lymph node dissection. Preoperative BMI, basal levels of TT, and prostate-specific antigen (PSA) were evaluated in 361 consecutive patients undergoing radical prostatectomy with extended pelvic lymph node dissection between 2014 and 2017. Patients were grouped into either nonmetastatic, one, or more than one metastatic lymph node invasion groups. The association among clinical factors and LNI was evaluated. LNI was detected in 52 (14.4%) patients: 28 (7.8%) cases had one metastatic node and 24 (6.6%) had more than one metastatic node. In the overall study population, BMI correlated inversely with TT (r = -0.256; P < 0.0001). In patients without metastases, BMI inversely correlated with TT (r = -0.282; P < 0.0001). In patients with metastasis, this correlation was lost. In the overall study population, BMI (odds ratio [OR] = 1.268; P = 0.005) was the only independent clinical factor associated with the risk of multiple metastatic LNI compared to cases with one metastatic node. In the nonmetastatic group, TT was lower in patients with BMI >28 kg m -2 (P < 0.0001). In patients with any LNI, this association was lost (P = 0.232). The median number of positive nodes was higher in patients with BMI >28 kg m -2 (P = 0.048). In our study, overweight and obese patients had a higher risk of harboring multiple prostate cancer lymph node metastases and lower TT levels when compared to patients with normal BMI., Competing Interests: None

Purpose: To assess associations of prostate volume index (PVI), defined as the ratio of the volume of the central transition zone to the volume of the peripheral zone of the prostate and prostatic chronic inflammation (PCI) as predictors of tumor load by number of positive cores (PC) in patients undergoing baseline random biopsies., Methods: Parameters evaluated included age, PSA, total prostate volume, PSA density, digital rectal exam, PVI, and PCI. All patients underwent standard transperineal random biopsies. Tumor load was evaluated as absent (no PC), limited (1-3 PC), and extensive (more than 3 PC). The association of factors with the risk of tumor load was evaluated by the multinomial logistic regression model., Results: The study evaluated 945 patients. Cancer PC were detected in 477 (507%) cases of whom 207 (43.4%) had limited tumor load and 270 (56.6%) had extensive tumor load. Among other factors, comparing patients with limited tumor load with negative cases, PVI [odds ratio, OR = 0.521, 95% confidence interval (CI) 0.330-0.824; p < 0.005] and PCI (OR = 0.289, 95% CI 0.180-0.466; p < 0.0001) were inversely associated with the PCA risk. Comparing patients with extensive tumor load with negative patients, PVI (OR = 0.579, 95% CI 0.356-0.944; p = 0.028), and PCI (OR = 0.150, 95% CI 0.085-0.265; p < 0.0001), predicted PCA risk. Comparing extensive tumor load with limited tumor load patients, PVI and PCI did not show any association with the tumor load., Conclusions: Increased PVI and the presence of PCI decreased the risk of increased tumor load and associated with less aggressive prostate cancer biology in patients at baseline random biopsies.

Background: The aim of this study is to evaluate factors (clinical, pathological and perioperative) associated with the risk of hospital readmission after radical prostatectomy (RP) over the long term in a single tertiary referral center where both open RP (ORP) and robot assisted RP (RARP) are performed., Methods: From January 2013 to December 2018 patients older than 18 years, who provided signed consent and underwent open or robot assisted radical prostatectomy were enrolled and retrospectively evaluated. Patients who underwent any previous prostate cancer (PCA) treatments were excluded. Specifically, skilled and experienced surgeons performed the two surgical approaches. Patients were followed for complications and hospital readmission (RAD) for a period of six months. The association of factors with the risk of readmission was assessed by Cox's multivariate proportional hazards., Results: A total of 1062 patients underwent RP. RARP was performed in 891 cases and ORP in 171 subjects. Extended pelvic lymph node dissection (ePLND) was performed in 651 patients. Hospital readmission occurred in 53 cases (5%). Based on the final multivariate model, independent factors associated with the risk of hospital readmission were seminal vesicle invasion (HR=2.093; 95% CI: 1.177-3.722), ORP (HR=4.393; 95% CI: 2.516-7.672) and ePLND (HR=4.418; 95% CI: 1.544-12.639)., Conclusions: ORP, ePLND and seminal vesicle invasion are independent predictors of the risk of hospital readmission over the long term at a large single tertiary referral center. When surgery is chosen as a primary treatment of PCA, patients should be informed of the risk of hospital readmission and related risk factors. Assessing seminal vesicle invasion by preoperative clinical staging identifies locally advanced disease, which is associated with an increased risk of hospital readmission.

Background: The aim of this study is to evaluate clinical factors associated with the risk of tumor upgrading patterns in low risk prostate cancer (PCA) patients undergoing radical prostatectomy., Methods: In a period running from January 2013 to December 2016, 245 low risk patients underwent RP. Patients were classified into three groups, which included case with pathology grade group one (no upgrading pattern), two-three (intermediate upgrading pattern), and four-five (high upgrading pattern). The association of factors with the upgrading risk was evaluated by the multinomial logistic regression model. It was used a receiver operating characteristic (ROC) curve and area under the curve (AUC) analysis to assess the efficacy of predictors., Results: Overall, tumor upgrading was detected in 158 patients (67.3%). Tumor upgrading patterns were absent in 80 patients (32.7%), intermediate in 152 cases (62%) and high in 13 subjects (5.3%). Median prostate specific (PSA) levels and proportion of biopsy positive core (BPC) were higher in patients with intermediate (PSA=6 ng/mL; BPC=0.28) and high (PSA=8.9 ng/mL; BPC=0.33) than those without (PSA=5.7 ng/mL; BPC=0.17) and the difference was significant (PSA: P=0.002; BPC: P=0.001). When compared to not upgraded cases, higher BPC proportions were independent predictors of intermediate upgrading patterns (odds ratio, OR=36.711; P<0.0001; AUC=0.613) while higher PSA values were independent predictors of high upgrading patterns (OR=2.033, P<0.0001; AUC=0.779)., Conclusions: PSA and BPC were both independent predictors of tumor upgrading in low risk PCA. BPC associated with the risk of intermediate tumor upgrading patterns, but showed a low discrimination power. PSA associated with high upgrading patterns and showed a fair discrimination power in the model. Tumor upgrading risk patterns should be evaluated in low risk PCA patients before treatment.

Objective: To test the hypothesis that basal total testosterone (TT) serum levels are associated with the D'Amico risk classification at diagnosis of prostate cancer (PCA)., Materials and Methods: From November 2014 to March 2018, preoperative basal levels of TT and prostate-specific antigen (PSA) were measured in 601 consecutive PCA patients who were not under androgen deprivation therapy or undergoing prior prostate surgery. Patients were classified into low (reference group), intermediate, and high risk classes according to biopsy findings. The association of TT and other clinical factors with risk classes was evaluated using a multivariate multinomial logistic regression model., Results: According to the D'Amico classification, 124 patients (24%) were low risk, 316 (52.6%) were intermediate risk, and 141 (23.4%) were high risk. Median basal TT circulating levels were significantly increased along clinical risk classes. TT along with PSA, percentage of biopsy positive cores, and tumor clinical stage were independently associated with a high risk (OR = 1.002; p = 0.022) but not with an intermediate risk of PCA when compared to the low risk class. In the intermediate-risk group, endogenous TT together with PSA were independently associated with tumor grade groups 2 (OR = 1.003; p = 0.022) and 3 (OR = 1.003; p = 0.043) compared to grade group 1 cancers., Conclusions: Basal TT levels are positively associated with the D'Amico risk classification, but the association is significant for the high-risk group compared to the low-risk group., (© 2020 S. Karger AG, Basel.)

Objectives: The aim of this study is to evaluate the association between total testosterone density (TTD), defined as the ratio of serum TT to prostate volume (PV), and high tumor load (HTL) in low-risk prostate cancer (PCA) patients who underwent radical prostatectomy., Materials and Methods: Tumor load was defined as the percentage of prostate volume invaded by cancer (PPI-PCA) in the surgical specimen. Pathologic features including tumor upgrading, upstaging or positive surgical margins in the specimen defined unfavorable disease (UD). PSA, TT, PSA density (PSAD), TTD, percentage of biopsy positive cores (BPC), PV and body mass index (BMI). The association of factors with the risk UD and HTL was evaluated by statistical methods., Results: The cohort included 144 consecutive low-risk PCA patients. Overall, 104 patients (72.2%) had at least one feature indicating UD. TTD was associated with BMI, TT, PSA, PV and PPI-PCA ≥ 20% defined as HTL. A higher PPI-PCA was associated with an increased risk of UD with a fair discriminant power (area under the curve, AUC = 0.775; p < 0.0001). Patients with PPI-PCA > 20% were considered the study group versus patients with a PPI-PCA < 20% (control group). BPC, PSAD and TTD were independently associated with the risk of HTL (PPI-PCA ≥ 20%) with receiver-operating characteristics (ROC) curves indicating the same discriminant power for BPC (AUC = 0.628; p = 0.013), PSAD (AUC = 0.611; p = 0.032) and TTD (AUC = 0.610; p = 0.032)., Conclusions: Among low-risk PCA patients, TTD is associated with the risk of HTL, which is an independent predictor of UD and should be evaluated in the management of these patients.

Background: The aim of this study was to investigate the risk factors contributing to multiple lymph node invasion (LNI) in patients with prostate cancer (PCa) undergoing extended pelvic lymph node dissection (ePLND) during robot assisted radical prostatectomy (RARP)., Methods: A total of 211 patients who underwent RARP and ePNLD from June 2013 to March 2017 were classified according to lymph node status in the surgical specimen (absent, single or multiple). Risk factors of LNI were evaluated by the multinomial logistic regression model. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to assess the efficacy of factors and model evaluation., Results: On multivariate analysis, the risk of multiple LNI, was independently increased by Body Mass Index (BMI) (odds ratio [OR] 1.194; P=0.026) and prostate-specific antigen (PSA) (OR=1.089; P=0.014) when compared to patients without LNI. ROC curves indicated that both BMI (AUC=0.702) and PSA (AUC=0.732) had fair discrimination power. For each unit of increase in PSA, the odds of multiple lymph node invasion increased by 8.9% and for each unit increase of BMI, the odds of multiple LNI increased by 19.4%., Conclusions: The risk of multiple LNI was independently predicted by PSA and BMI with fair discrimination power.

Background: The aim of this study was to assess the anatomical prevalence and secondary involvement of Cloquet's nodes in patients undergoing robotic radical prostatectomy (RRP) and extended pelvic lymph node dissection (ePLND) for prostate cancer (PCa)., Methods: RRP and ePLND were performed by two expert surgeons (WA and VDM). Data were prospectively collected and retrospectively analyzed. Dissected pelvic lymph nodes were sampled according to an anatomical template as follows: external iliac, obturator, Marcille's, and Cloquet's. Node packages were sent to the dedicated pathologist separately. Baseline characteristics, perioperative and pathological outcomes were analyzed., Results: Between January 2014 and December 2017 a total of 258 patients were evaluated. In aggregate 247 out of 258 patients (95.7%) presented at least a lymph node in the in the Cloquet's fossa tissue and 105 (40.6%) had more than one node. Patients with multiple nodes in Cloquet fossa presented higher median lymph node amount (27 vs. 33; P<0.0001). 13.5% of patients had lymph node invasion Pathological evaluation of the Cloquet's nodes showed metastatic PCa in 3 out of 35 (8.6%) pN+ patients. No differences were found when patients with metastatic Cloquet's nodes were compared with the pN+ population in terms of demographics, PSA, D'Amico classification, biopsy and pathological Gleason Grouping, clinical and pathological stage and complications., Conclusions: To the best of our knowledge this is the first study that analyses specifically the quantitative prevalence of Cloquet's nodes and the incidence of malignancy involvement in patients undergoing RRP and ePLND for PCa. The occurrence of multiple lymph nodes in the Cloquet fossa is a rare event. Our series showed that Cloquet involvement seems to be associated with multiple nodes cohabitation and contemporarily multiple lymph node metastases in other template locations. Related morbidity rate is sporadic and cannot justify the Cloquet preservation. Wider series are required to comprehend predictor factors of Cloquet nodes involvement. Until then the Cloquet lymphadenectomy would be recommended and should not be an option.

Robot assisted radical prostatectomy (RARP) with extensive pelvic lymph node dissection (ePLND) is an effective procedure for treating and staging prostate cancer; however, high grade complications represent a critical issue. To investigate clinical factors associated with the risk of Clavien-Dindo grade 3 complications in patients undergoing RARP with ePLND. The study included 211 consecutive patients who were operated in a period running from June 2013 to March 2017. Factors associated with grade 3 complications were evaluated by the logistic regression model. Receiver operating characteristic curves and area under the curve (AUC) were used to assess the risk model. Of the 211 patients included in the study, 55 (26.1%) had complications, which were classified Clavien grade one in 36 cases (17.1%), two in 7 (3.3%), 3a in 9 (4.3%) and 3b in 3 (1.4%). Higher median measurements of body mass index (BMI) were detected in grade 3 subjects (27.6 kg/m 2 ) when compared to grade 0-2 cases (25 kg/m 2 ) and the difference was significant (P = 0.015). BMI increased the risk of high grade complications (odds ratio, OR 1.184; P = 0.047) with a fair discrimination power (AUC 0.709). It generated a risk curve by the model, which stratified patients in low (BMI < 26 kg/m 2 ; probability risk less than 5%), intermediate (26 ≤ BMI (kg/m 2 ) ≤ 30; risk between 5 and 10%), and high (BMI > 30 kg/m 2 ; risk between 10 and 20%) risk classes for grade 3 complications. BMI is an independent predictor of grade 3 complications, which are increased by 18.4% for each unit rise. Patients may be stratified preoperatively by BMI into grade 3 risk categories, which include low (normal weight), intermediate (overweight), and high (obese) risk cases.

Introduction: To evaluate the association between preoperative serum prolactin (PRL) levels and risk of non-organ confined prostate cancer (PCa) in clinically localized disease., Materials and Methods: From December 2007 to December 2011, 124 patients with clinically localized PCa were retrospectively evaluated. Non-organ confined disease in the surgical specimen was defined according to extra-capsular extension, seminal vesicle invasion, positive surgical margins, and lymph node invasion. The association between clinical factors and serum levels of pituitary-testis hormones with the risk of non-organ confined disease was evaluated., Results: Perioperative factors associated with non-organ confined disease include prostatic-specific antigen (OR 1.144; p = 0.025), proportion of biopsy positive cores (BPC, OR 36.702; p = 0.007), bioptical Gleason Score > 6 (OR 2.785; p = 0.034), and PRL (OR 0.756, p < 0.0001). The association was strong for BPC (area under the curve [AUC] 0.704; p < 0.0001) and PRL (AUC 0.299; p < 0.0001). When we dichotomized according to median value, PRL ≤7.7 µg/L was an independent predictor of extraprostatic disease (OR 6.571; p < 0.0001) with fair discrimination power (AUC 0.704; p < 0.0001)., Conclusion: Low preoperative PRL levels predict the risk of non-organ confined PCa in clinically localized disease., (© 2019 S. Karger AG, Basel.)

Introduction: To test the hypothesis that basal total testosterone (TT) levels are associated with International Society of Urologic Pathology (ISUP) tumor grade groups at the time of diagnosis of prostate cancer (PCA)., Methods: From November 2014 to March 2018, preoperative TT and PSA were measured in 601 consecutive patients who were not under androgen deprivation and undergoing surgery for PCA. Patients were classified into low (ISUP 1; reference group), intermediate (ISUP 2/3), and high (ISUP 4/5) tumor grade groups. The association of TT and other clinical factors with tumor groups was evaluated by multinomial multivariate regression analysis., Results: 218 patients (36.3%) were biopsy low grade (ISUP 1), 297 (49.4%) intermediate grade (ISUP 2/3), and 86 (14.3) high grade (ISUP 4/5). Median basal circulating TT levels progressively increased as tumor grade groups increased. On multivariate models, TT, among other clinical factors, was positively associated with the risk of intermediate (OR 1.001; p = 0.023) and high tumor grades (OR 1.002, p = 0.022) compared to low-grade cancers., Conclusions: Increased endogenous circulating basal TT levels were positively associated with ISUP tumor grade groups at the time of diagnosis indicating a close association with tumor biology. Basal TT levels may reflect the heterogeneity of the cancer population., (© 2019 S. Karger AG, Basel.)

Introduction: To assess the association of prostate volume index (PVI), defined as the ratio of the central transition zone volume to the peripheral zone volume, and prostatic chronic inflammation (PCI) as predictors of prostate cancer (PCA) risk in patients presenting with normal digital rectal exam and prostate-specific antigen (PSA) ≤10 ng/mL at baseline random biopsies., Methods: We evaluated patients with a negative digital rectal examination (DRE) and a PSA ≤10 ng/mL who underwent initial baseline prostate biopsy from 2010 to 2017. Parameters evaluated included age, PSA, total prostate volume (TPV), PSA density (PSAD), PVI and PCI. All patients underwent 14 core trans-perineal standard biopsies. The association of factors with the risk of PCA was evaluated by logistic regression analysis, utilizing 2 multivariate models: model I included age, TPV, PVI and PCI; model II included age, PSAD, PVI and PC., Results: Overall, 564 Caucasian patients were included. PCA and PCI were detected in 242 (42.9%) and 129 (22.9%) cases respectively. In patients with PCA, the median PVI was 0.83 (interquartile range [IQR] 0.62-1.04). In patients with PCI, the median PVI was 1.12 (IQR 0.81-1.47). In model I, age (OR 1.080) TPV (OR 0.961), PVI (OR 0.517) and PCI (OR 0.249) were associated with PCA risk. In model II, the age (OR 1.074), PSAD (OR 3.080), PVI (OR 0.361) and PCI (OR 0.221) were associated with PCA risk., Conclusions: Higher PVI and PCI predicted decreased PCA risk in patients presenting with normal DRE, and a PSA ≤10ng/mL at baseline random biopsy. In this subset of patients, PVI is able to differentiate patients with PCI or PCA., (© 2019 S. Karger AG, Basel.)

Introduction: To assess the incidence of malignancy involvement of lymph nodes (LNs) in Marcille's fossa in patients undergoing robot assisted radical prostatectomy (RARP) and extended pelvic lymph nodes dissection (ePLND) for prostate cancer (PCa)., Design, Setting, and Participants: Between January 2014 and December 2017, details of patients who underwent RARP and ePLND were prospectively analysed. All the nodal packets were dissected separately, grouped into left and right nodes and submitted in separate packages to dedicated pathologist., Results and Limitations: Two hundred and twenty-one patients underwent ePLND and RARP in the study period. In aggregate, Marcille's LNs involvement was found in 5 (2.3%) of patients, 2 on the left side and 3 on the right side. Per cent of positive cores and Gleason at biopsy are clinical predictors of LNs invasion; moreover, in the surgical specimen, seminal vesicle invasion and high-grade cancer were factors related to loco-regional metastases., Conclusions: Marcille's nodes involvement is associated to contemporarily multiple LN metastases in other template locations in high-risk PCa patients. The Marcille's lymphadenectomy would be recommended when planning an ePLND in high-risk PCa., (© 2019 S. Karger AG, Basel.)

Objective: To evaluate clinical predictors of lymph node invasion (LNI) in patients with high-risk prostate cancer undergoing radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND)., Methods: A contemporary cohort of 116 patients, who underwent ePLND during RP, was retrospectively evaluated. Patients were classified into 3 groups including cases without LNI (group 1), with 1 to 3 positive nodes (group 2; limited LNI), and with more than 3 positive nodes (group 3; extensive LNI). The multinomial logistic regression model (multivariate analysis) evaluated the risk of LNI., Results: Overall, 30 patients (25.9%) had LNI, which was limited in 17 cases (14.7%) and extensive in 13 subjects (11.2%). Median prostate-specific antigen (PSA) was higher in cases with limited (11.4 ng/mL) or extensive (23.5 ng/mL) LNI than cases without (7.3 ng/mL) and the difference was significant ( p <.0001). Median proportion of biopsy-positive cores was higher in limited (0.64) or extensive (0.54) LNI than cases without (0.34) and the difference was significant ( p < .0001). The distribution of other factors did not show any significant difference among the groups. On multivariate analysis, only higher values of PSA significantly affected the odds of extensive LNI when compared to cases without (odds ratio, 1.054; p = .005); PSA showed a fair discrimination power (area under the curve 0.792)., Conclusion: PSA was the only independent predictor of extensive LNI and could be an important preoperative factor for stratifying high-risk patients.

Introduction: The cardiovascular toxicity related to abiraterone and enzalutamide has been previously studied by our group. In this analysis, we aim to update our previous findings related to abiraterone and enzalutamide, including the new available evidence, both in castration-resistant and hormone-sensitive prostate cancer. PATIENTS AND METHODS: Prospective studies were identified by searching the MEDLINE/PubMed, Cochrane Library, and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods., Results: We included 7 articles in this meta-analysis, covering a total of 8660 patients who were used to evaluate cardiovascular toxicity. The use of new hormonal agents was associated with an increased risk of all-grade (RR, 1.36; 95% CI, 1.13-1.64; P = .001) and high-grade (RR, 1.84; 95% CI, 1.21-2.80; P = .004) cardiac toxicity. The use of new hormonal agents was also associated with an increased risk of all-grade (RR, 1.98; 95% CI, 1.62-2.43; P = .001) and high-grade (RR, 2.26; 95% CI, 1.84-2.77; P = .004) hypertension compared with the controls. Abiraterone was found to significantly increase the risk of both cardiac toxicity and hypertension, whereas enzalutamide significantly increases only the risk of hypertension. No differences were found based on the dose of prednisone used with abiraterone. The major limitation of this study is that data are available only as aggregate, and no single-patient information could be analyzed., Conclusions: Abiraterone and enzalutamide significantly increase the incidence and RR of cardiovascular toxicity in patients affected by metastatic prostate cancer. Follow-up for the onset of treatment-related cardiovascular events should therefore be considered in these patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To identify clinical factors stratifying the risk of tumor upgrading to increasing patterns of the tumor grading system in low-risk prostate cancer (PCa)., Methods: We evaluated the records of 438 patients who underwent radical prostatectomy. Associations between clinical factors and tumor upgrading were assessed by the univariate and multivariate multinomial logistic regression model., Results: Low-risk PCa included 170 cases (38.8%) and tumor upgrading was detected in 111 patients (65.3%): 72 (42.4%) had pathology Gleason pattern (pGP) 3 + 4, 27 (15.9%) pGP 4 + 3, and 12 (7.1%) pGP 4 + 4. Prostate- specific antigen (PSA) and proportion of positive cores (P+) were independent predictors of upgrading to high-risk disease. These factors also stratified the risk of tumor upgrading to the increasing patterns of the tumor grading system. The model allowed the identification of pGP 4 + 4. The main difference between high-risk PCa and other upgraded tumors related to PSA load (odds ratio 2.4) that associated with high volume disease in the specimen., Conclusions: Low-risk PCa is a heterogeneous population with significant rates of tumor upgrading. Significant clinical predictors stratifying the risk of tumor upgrading to increasing patterns of the grading system included PSA and P+. These factors allowed the identification of the subset hiding high-grade disease requiring further investigations before delivering active treatments.