Prognostic Impact and Clinical Implications of Adverse Tumor Grade in Very Favorable Low- and Intermediate-Risk Prostate Cancer Patients Treated with Robot-Assisted Radical Prostatectomy: Experience of a Single Tertiary Referral Center.

OBJECTIVES: To assess the prognostic impact and predictors of adverse tumor grade in very favorable low- and intermediate-risk prostate cancer (PCa) patients treated with robot-assisted radical prostatectomy (RARP). METHODS: Data of low- and intermediate PCa risk-class patients were retrieved from a prospectively maintained institutional database. Adverse tumor grade was defined as pathology ISUP grade group > 2. Disease progression was defined as a biochemical recurrence event and/or local recurrence and/or distant metastases. Associations were assessed by Cox's proportional hazards and logistic regression model. RESULTS: Between January 2013 and October 2020, the study evaluated a population of 289 patients, including 178 low-risk cases (61.1%) and 111 intermediate-risk subjects (38.4%); unfavorable tumor grade was detected in 82 cases (28.4%). PCa progression, which occurred in 29 patients (10%), was independently predicted by adverse tumor grade and biopsy ISUP grade group 2, with the former showing stronger associations (hazard ratio, HR = 4.478; 95% CI: 1.840-10.895; p = 0.001) than the latter (HR = 2.336; 95% CI: 1.057-5.164; p = 0.036). Older age and biopsy ISUP grade group 2 were independent clinical predictors of adverse tumor grade, associated with larger tumors that eventually presented non-organ-confined disease. CONCLUSIONS: In a very favorable PCa patient population, adverse tumor grade was an unfavorable prognostic factor for disease progression. Active surveillance in very favorable intermediate-risk patients is still a hazard, so molecular and genetic testing of biopsy specimens is needed.

Tumor upgrading among very favorable intermediate-risk prostate cancer patients treated with robot-assisted radical prostatectomy: how can it impact the clinical course?

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.

Prognostic impact of palpable prostate tumors on disease progression after robot-assisted radical prostatectomy: a single-center experience.

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.

Impairment in Activities of Daily Living Assessed by the Barthel Index Predicts Adverse Oncological Outcomes After Radical Cystectomy for Bladder Cancer.

INTRODUCTION: We tested the association between functional impairment in activities of daily living (ADL) assessed through the Barthel Index (BI), and oncological outcomes following radical cystectomy (RC) for bladder cancer (BCa). PATIENTS AND METHODS: We retrospectively analyzed data of 262 clinically nonmetastatic BCa patients, who underwent RC between 2015 and 2022, with available follow-up. According to preoperative BI, patients were divided in 2 groups: BI ≤90 (moderate/severe/total dependency in ADL) versus BI 95 to 100 (slight dependency/independency in ADL). Kaplan-Meier plots compared disease recurrence (DR)-, cancer-specific mortality (CSM)-, and overall mortality (OM)-free survival according to established categories. Multivariable Cox regression models tested the BI as an independent predictor of oncological outcomes. RESULTS: According to the BI, the patient cohort was distributed as follows: 19% (n = 50) BI ≤90 versus 81% (n = 212) BI 95-100. Compared to patients with BI 95 to 100, patients with BI ≤90 were less likely to receive intravesical immuno- or chemotherapy (18% vs. 34%, p = .028), and more frequently underwent less complex urinary diversion as ureterocutaneostomy (36% vs. 9%, p < .001), or harbored muscle-invasive BCa at final pathology (72% vs. 56%, p = .043). In multivariable Cox regression models adjusted for age, ASA physical status score, pathological T and N stage, and surgical margins status, BI ≤90 independently predicted higher DR (HR [hazard ratio]:2.00, 95%CI [confidence interval]:1.21-3.30, p = .007), CSM (HR:2.70, 95%CI:1.48-4.90, p = .001), and OM (HR:2.09, 95%CI:1.28-3.43, p = .003). CONCLUSION: Preoperative impairment in ADL was associated with adverse oncological outcomes following RC for BCa. The integration of the BI into clinical practice may improve the risk assessment of BCa patients candidates to RC.

Impact of functional impairment and cognitive status on perioperative outcomes and costs after radical cystectomy: The role of Barthel Index.

OBJECTIVES: To investigate the association between Barthel Index (BI), which measures level of patients independence during daily living activities (ADL), and perioperative outcomes in a large cohort of consecutive bladder cancer (BCa) patients, who underwent radical cystectomy (RC) at a tertiary referral center. METHODS: We retrospectively evaluated data from clinically nonmetastatic BCa patients treated with RC between 2015 and 2022. For each patient, BI was assessed preoperatively. According to BI score, patients were divided into three groups: ≤60 (total/severe dependency) vs. 65-90 (moderate dependency) vs. 95-100 (slight dependency/independency). Regression analyses tested the association between BI score and major postoperative complications (Clavien-Dindo >2), length of in-hospital stay (LOHS), 90-days readmission, and total costs. RESULTS: Overall, 288 patients were included. According to BI score, the patient cohort was distributed as follows: 4% (n = 11) BI ≤60 vs. 15% (n = 42) BI 65-90 vs. 81% (n = 235) BI 95-100. Patients with BI ≤60 had more frequent ureterocutaneostomy performed, shorter operative time, higher rates of postoperative complications, longer LOHS, higher rates of readmission, and were associated with higher total costs, compared to patients with BI 65-90 and 95-100. In multivariable regression models, BI ≤60 remained an independent predictor of increased risk of major postoperative complications (odds ratio: 6.62, p = 0.006), longer LOHS (rate ratio: 1.25, p < 0.001), and higher costs (ß: 2.617, p = 0.038). CONCLUSIONS: Total/severe dependency in ADL assessed by BI was associated with higher rates of major postoperative complications, longer hospitalization, and higher costs in BCa patients treated with RC. BI assessment should be considered during patients selection process and counseling before surgery.

Features of patients referring to the outpatient office due to benign prostatic hyperplasia: analysis of a national prospective cohort of 5815 cases.

BACKGROUND: Evidence on clinical presentation of benign prostatic hyperplasia (BPH) is scarce, and studies involving outpatients are lacking. We aimed to provide an insight into the contemporary Italian scenario of BPH-affected outpatients using symptom scores (International Prostate Symptom Score [IPSS], BPH Impact Index [BII]), and to compare characteristics of patients with known BPH and those first-diagnosed at the visit. METHODS: "IMPROVING THE PATH" project working group designed a questionary prospectively administered to BPH-affected outpatients by urologists. A cross-sectional study was performed. Data were adjusted for patient age as a potential confounding factor. RESULTS: Of 5815 patients enrolled, BPH was already diagnosed in 4144 (71.3%), and not in 1671 (28.7%). Patients with known BPH, compared to newly diagnosed, were older (median 68 versus [vs] 55), had more frequent smoking (smoker 27.2 vs 22.6%, and ex-smoker 16.4 vs 12.5%) and drinking habits (55.4 vs 45.1%), were more frequently affected by hypertension (60.0 vs 42.4%), obesity (15.3 vs 9.6%), diabetes (17.9 vs 12.5%), and cardiovascular diseases (14.2 vs 9.5%), p < 0.001. At IPSS, moderate and severe symptoms correlated with already known BPH (56.1 vs 47.3% and 24.8 vs 7.8%), whereas newly diagnosed patients showed milder symptoms (44.9 vs 19.1%), all p < 0.001. At BII, concern for one's health and time lost due to urinary problems were higher in patients with known BPH (p < 0.001). For these patients, the urologist changes at least one of the ongoing medications in 63.5%. For patients newly diagnosed, supplements/phytotherapeutics, alpha-blockers, and 5-alfa reductase inhibitors were prescribed in 54.6%, 21.6%, and 7.1%, respectively. CONCLUSIONS: Despite medical treatment, natural history of BPH leads to a progressive deterioration of symptoms. This may reflect the difference between newly diagnosed patients and those with known BPH in lifestyle and associated comorbidities. A healthy lifestyle and treatments including local anti-inflammatory agents may delay worsening of symptoms and improve quality of life.

AB0 blood groups and oncological and functional outcomes in bladder cancer patients treated with radical cystectomy.

OBJECTIVES: We investigated AB0 blood groups prevalence according to preoperative and pathological tumor characteristics, and their association with oncological outcomes, and renal function decline in a contemporary large cohort of bladder cancer (BCa) patients, who underwent radical cystectomy (RC) at a tertiary referral center. MATERIALS AND METHODS: We retrospectively evaluated data of patients with histologically confirmed and clinically non metastatic BCa, who underwent RC between 2014 and 2021 at our Institution. Kaplan-Meier (KM) plots and Cox regression (CR) models tested the relationship between AB0 blood groups and local recurrence-, metastasis-, cancer specific mortality-, and overall mortality-free survival. Logistic regression (LR) models tested the association between AB0 blood groups and renal function decline, defined as an estimated Glomerular Filtration Rate (eGFR) < 60 mL/min, at post-operative day 1, discharge and 6- months of follow-up. RESULTS: Of 301 included patients, 128 (42.5%) had group A, 126 (41.9%) had group 0, 28 (9.3%) had group B, and 19 (6.3%) had group AB. Patients with group 0 developed higher rates of muscle- invasive BCa (p = 0.028) with high-grade features (p = 0.005) at last bladder resection, and less frequently received preoperative immunotherapy with Bacillus of Calmette-Guerin (p = 0.044), than their non-0 counterparts. Additionally, these patients harbored more advanced pathologic tumor stage at RC (p = 0.024). KM plots showed no differences among all tested cancer control outcomes between AB0 blood groups (p > 0.05 in all cases). Patients with group AB presented the lowest median eGFR at each time point. In multivariable LR analyses addressing renal function decline, group AB was independently associated with eGFR< 60 mL/min at discharge (Odds Ratio: 4.28, p = 0.047). CONCLUSIONS: Among AB0 blood groups, patients with group 0 exhibited the most aggressive tumor profile. However, no differences were recorded in recurrence or survival rates. Group AB independently predicted renal function decline at discharge.

Variant histologies in bladder cancer: Does the centre have an impact in detection accuracy?

OBJECTIVE: To compare the accuracy in detecting variant histologies (VH) at transurethral resection of bladder (TURB) and radical cystectomy (RC) specimen among tertiary referral centres, in order to investigate potential reasons of discrepancies from the pathological point of view. PATIENTS AND METHODS: Clinical and histopathological data of TURB specimen and subsequent cystectomy specimen of 3,445 RC candidate patients have been retrospectively collected from 24 tertiary referral centres between 1980 and 2021. VH considered in the analysis were pure squamous cell carcinoma, urothelial carcinoma with squamous differentiation, pure adenocarcinoma, urothelial carcinoma with glandular differentiation, micropapillary bladder cancer (BCa), neuroendocrine BCa, and other variants. The degree of agreement between TURB and RC concerning the identification of VH was expressed as concordance, classified according to Cohen's kappa coefficient. RESULTS: A VH was reported in 17% of TURB specimens, 45% of which were not confirmed in RC. The lowest concordance rate was reported for micropapillary BCa with 11 out of 18 (61%) centres reporting no agreement, whereas neuroendocrine BCa achieved the highest concordance rate with only 3 centres (17%) reporting no agreement. Our results shows that even among centres with the advantage of a referent uropathologist the micropapillary variant is characterized by scarce accuracy between TURB and RC. Differences in TURB specimen acquisition by the urologist and in sampling methods among different centres are the main limitations of the study. CONCLUSIONS: Accuracy of TURB in detecting VH is poor for certain VH, in particular for micropapillary BCa, with evident variation among centres. Novel diagnostic tools are required to better identify these VH and drive patients toward a personalized treatment.

Predictors of complications occurring after open and robot-assisted prostate cancer surgery: a retrospective evaluation of 1062 consecutive patients treated in a tertiary referral high volume center.

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.

Accuracy of Transurethral Resection of the Bladder in Detecting Variant Histology of Bladder Cancer Compared with Radical Cystectomy.

BACKGROUND: Correct identification of variant histologies (VHs) of bladder cancer (BCa) at transurethral resection of the bladder (TURB) could drive the subsequent treatment. OBJECTIVE: To evaluate the concordance in detecting VHs between TURB and radical cystectomy (RC) specimens in BCa patients. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively analyzed 1881 BCa patients who underwent TURB and subsequent RC at seven tertiary care centers between 1980 and 2018. VHs were classified as sarcomatoid, lymphoepithelioma-like, neuroendocrine, squamous, micropapillary, glandular, adenocarcinoma, nested, and other variants. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Concordance between TURB and RC was defined as the ability to achieve histological subtypes at TURB confirmed at RC specimen, and was expressed according to Cohen's kappa coefficient. RESULTS AND LIMITATIONS: Of the patients, 14.6% and 21% were diagnosed with VH at TURB and RC specimens, respectively. The most common VHs at TURB were squamous, neuroendocrine, and micropapillary carcinoma (5.2%, 1.5%, and 1.5%, respectively). At RC, the most frequent VHs were squamous, micropapillary, and sarcomatoid carcinoma (7.2%, 3.0%, and 2.7%, respectively). The overall concordance in detecting VH was defined as slight concordance (coefficient: 0.18). Moderate concordance was found for neuroendocrine, adenocarcinoma, and squamous carcinoma (coefficient: 0.49, 0.47, and 0.41, respectively). Micropapillary, glandular, and other variants showed slight concordance (coefficient: 0.05, 0.17, and 0.12, respectively), while nested and sarcomatoid carcinoma showed fair concordance (coefficient: 0.32 and 0.26, respectively). Results may be limited by the absence of centralized pathological analysis. CONCLUSIONS: A non-negligible percentage of patients were diagnosed with VH at both TURB and RC. TURB showed relatively low accuracy, ranging from poor to moderate, in detecting VHs. Our study underlines the need of additional diagnostic tools in order to identify VHs properly at precystectomy time and to improve patient survival outcomes. PATIENT SUMMARY: In this report, we underlined the low accuracy of transurethral resection of the bladder in detecting variant histologies and the need for additional diagnostic tools.

Association between ABO blood group and unfavorable prostate cancer features after radical prostatectomy: Retrospective study of 1149 patients.

Objectives: To test hypothesized associations between the ABO blood group (ABO-bg) system and the pathological features of prostate cancer (PCa). Material and methods: Between January 2013 and September 2019, 1173 patients underwent radical prostatectomy. Associations between ABO-bg levels and pathological features were evaluated using statistical methods. Results: Overall, 1149 consecutive patients were evaluated using the ABO-bg system, which was represented by O-bg (42.8%) and A-bg (41.3%), followed by B-bg (11.1%) and AB-bg (4.8%). Only positive surgical margins (PSMs) was correlated with ABO-bg (Pearson correlation coefficient, r = 0.071; p = 0.017), and the risk was increased in group-O (odds ratio [OR], 1.497; 95% confidence interval, 1.149-1.950; p = 0.003) versus non-O-bg. In clinical and pathological models, O-bg was at increased risk of PSM after the adjustment for prostate-specific antigen, percentage of biopsy-positive cores, and high surgical volume (adjusted OR, 1.546; 95% confidence interval, 1.180-2.026; p = 0.002); however, the adjusted OR did not change after the adjustment for tumor load and stage as well as high surgical volume. Conclusions: In clinical PCa, the risk of PSM was higher in O-bg versus non-O-bg patients after the adjustment for standard predictors. Confirmatory studies are needed to confirm the association between ABO-bg and unfavorable PCa features.

Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3-T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3-T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. MATERIALS AND METHODS: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). RESULTS: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75-0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32-0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58-1.35; p = 0.58). CONCLUSIONS: The administration of AC in patients with MIBC and pT3-T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients.

The impact of preoperative nutritional status on post-surgical complication and mortality rates in patients undergoing radical cystectomy for bladder cancer: a systematic review of the literature.

PURPOSE: To investigate the impact of preoperative nutritional factors [body mass index (BMI)], hypoalbuminemia (< 3.5 g/dL, sarcopenia) on complication and mortality rates after radical cystectomy (RC) for bladder cancer. METHODS: The PubMed database was systematically searched for studies investigating the effect of nutritional status on postoperative outcomes after RC. English-language articles published between March 2010 and March 2020 were reviewed. For statistical analyses odds ratios (ORs) and hazard ratios (HRs) weighted mean was applied. RESULTS: Overall, 81 studies were included. Twenty-nine studies were enrolled in the final analyses. Patients with a 25-29.9 kg/m2 BMI (OR 1.55, 95% confidence interval [CI] 1.14-2.07) and those with a BMI ≥ 30 kg/m2 (OR 1.73, 95% CI 1.29-2.40) had a significantly increased risk of 30 day complications after RC. Preoperative hypoalbuminemia increased the risk of 30 day complications (OR 1.56, 95% CI 1.07-2.35); it was a predictor of worse 3 year overall survival (OS) (HR 1.86, 95% CI 1.32-2.66). Sarcopenic patients had a higher risk of 90 day complications than non-sarcopenic ones (OR 2.49, 95% CI 1.22-5.04). Sarcopenia was significantly associated with unfavorable 5 year cancer-specific survival (CSS) (HR 1.73, 95% CI 1.07-2.80), and OS (HR 1.60, 95% CI 1.13-2.25). CONCLUSION: High BMI, hypoalbuminemia, and sarcopenia significantly increased the complication rate after RC. Hypoalbuminemia predicted worse 3 year OS and sarcopenia predicted unfavorable 5 year CSS and OS. Preoperative assessment of RC patients' nutritional status is a useful tool to predict perioperative and survival outcomes.

Basal total testosterone serum levels predict biopsy and pathological ISUP grade group in a large cohort of Caucasian prostate cancer patients who underwent radical prostatectomy.

AIMS: The study aimed to evaluate associations of preoperative total testosterone (TT) with the risk of aggressive prostate cancer (PCA). MATERIALS & METHODS: From 2014 to 2018, basal TT levels were measured in 726 consecutive PCA patients. Patients were classified according to the International Society of Urologic Pathology (ISUP) system. Aggressive PCA was defined by the detection of ISUP > 2 in the surgical specimen. The logistic regression model evaluated the association of TT and other clinical factors with aggressive PCA. RESULTS: On univariate analysis, there was a significant association of basal TT with the risk of aggressive PCA as well as age, prostate-specific antigen (PSA), percentage of biopsy positive cores (BPC), tumor clinical stage (cT), and biopsy ISUP grade groups. On multivariate analysis, two models were considered. The first (model I) excluded biopsy ISUP grading groups and the second (model II) included biopsy ISUP grade groups. Multivariate model I, revealed TT as well as all other variables, was an independent predictor of the risk of aggressive disease [odds ratio (OR) = 1.585; 95% confidence interval (CI): 1.113-2.256; p = 0.011]. Elevated basal PSA greater than 20 µg/dl was associated with the risk of aggressive PCA. Multivariate model II revealed that basal TT levels maintain a positive association between aggressive PCA, whereas age, BPC, and clinical stage cT3 lost significance. In the final adjusted model, the level of risk of TT did not change from univariate analysis (OR = 1.525; 95% CI: 1.035-2.245; p = 0.011). CONCLUSION: Elevated preoperative TT levels are associated with the risk of aggressive PCA in the surgical specimen. TT may identify patients who are at risk of aggressive PCA in the low and intermediate European Association of Urology (EAU) risk classes.