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Additional file 1:Supplementary material. Table S1. ESSEN1 gene set. Table S2. ESSEN2 gene set. Figure S1. Comparison of correlation p-value between for samples older and younger than five years for MACE and HTG. Figure S2. Pearson’s correlation between samples and each consensus class stratified for the different methods and for the called consensus class. Figure S3. Relative distribution of subtype calls with each method and gene panels. Figure S4. A: Comparison of p-values associated to the Pearson’s correlation of the samples with the nearest centroid for each method (HTG and MACE) for the ESSEN1 and ESSEN2 gene panels. Figure S5. Pearson’s correlation between samples and each consensus class stratified for the different gene sets.

Background: Molecular subtypes predict prognosis in muscle-invasive bladder cancer (MIBC) and are explored as predictive markers. To provide a common base for molecular subtyping and facilitate clinical applications, a consensus classification has been developed. However, methods to determine consensus molecular subtypes require validation, particularly when FFPE specimens are used. Here, we aimed to evaluate two gene expression analysis methods on FFPE samples and to compare reduced gene sets to classify tumors into molecular subtypes. Methods: RNA was isolated from FFPE blocks of 15 MIBC patients. Massive analysis of 3’ cDNA ends (MACE) and the HTG transcriptome panel (HTP) were used to retrieve gene expression. We used normalized, log2-transformed data to call consensus and TCGA subtypes with the consensusMIBC package for R using all available genes, a 68-gene panel (ESSEN1), and a 48-gene panel (ESSEN2). Results: Fifteen MACE-samples and 14 HTP-samples were available for molecular subtyping. The 14 samples were classified as Ba/Sq in 7 (50%), LumP in 2 (14.3%), LumU in 1 (7.1%), LumNS in 1 (7.1%), stroma-rich in 2 (14.3%) and NE-like in 1 (7.1%) case based on MACE- or HTP-derived transcriptome data. Consensus subtypes were concordant in 71% (10/14) of cases when comparing MACE with HTP data. Four cases with aberrant subtypes had a stroma-rich molecular subtype with either method. The overlap of the molecular consensus subtypes with the reduced ESSEN1 and ESSEN2 panels were 86% and 100%, respectively, with HTP data and 86% with MACE data. Conclusion: Determination of consensus molecular subtypes of MIBC from FFPE samples is feasible using various RNA sequencing methods. Inconsistent classification mainly involves the stroma-rich molecular subtype, which may be the consequence of sample heterogeneity with (stroma)-cell sampling bias and highlights the limitations of bulk RNA-based subclassification. Classification is still reliable when analysis is reduced to selected genes. CA extern

Objective: To analyze the influence of biopsy Gleason score on the risk for lymph node invasion (LNI) during pelvic lymph node dissection (PLND) in patients undergoing radical prostatectomy (RP) for intermediate-risk prostate cancer (PCa). Materials and Methods: We retrospectively analyzed 684 patients, who underwent RP between 2014 and June 2020 due to PCa. Univariable and multivariable logistic regression, as well as binary regression tree models were used to assess the risk of positive LNI and evaluate the need of PLND in men with intermediate-risk PCa. Results: Of the 672 eligible patients with RP, 80 (11.9%) men harbored low-risk, 32 (4.8%) intermediate-risk with international society of urologic pathologists grade (ISUP) 1 (IR-ISUP1), 215 (32.0%) intermediate-risk with ISUP 2 (IR-ISUP2), 99 (14.7%) intermediate-risk with ISUP 3 (IR-ISUP3), and 246 (36.6%) high-risk PCa. Proportions of LNI were 0, 3.1, 3.7, 5.1, and 24.0% for low-risk, IR-ISUP1, IR-ISUP 2, IR-ISUP-3, and high-risk PCa, respectively (p < 0.001). In multivariable analyses, after adjustment for patient and surgical characteristics, IR-ISUP1 [hazard ratio (HR) 0.10, p = 0.03], IR-ISUP2 (HR 0.09, p < 0.001), and IR-ISUP3 (HR 0.18, p < 0.001) were independent predictors for lower risk of LNI, compared with men with high-risk PCa disease. Conclusions: The international society of urologic pathologists grade significantly influence the risk of LNI in patients with intermediate- risk PCa. The risk of LNI only exceeds 5% in men with IR-ISUP3 PCa. In consequence, the need for PLND in selected patients with IR-ISUP 1 or IR-ISUP2 PCa should be critically discussed.

Advanced stage metastatic prostate cancer with extensive bone marrow involvement is associated with a high risk of therapy-induced myelotoxicity and unfavorable outcomes. The role of salvage radioligand therapy (RLT) with 177Lu-PSMA-617 in this subset of patients remains to be further elucidated. Forty-five patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and diffuse bone marrow involvement were treated with repeated cycles of RLT after having exhausted standard treatment options. A mean treatment activity of 7.4 ± 1.4 GBq 177Lu-PSMA-617 was administered in a median of four treatment cycles (IQR 2-6) and the mean cumulative activity was 32.6 ± 20.1 GBq. After two RLT cycles, ≥50% PSA decline was observed in 25/45 (56%) patients and imaging-based partial remission (PR) was observed in 18/45 (40%) patients. Median imaging-based progression-free survival (PFS) was 6.4 mo (95% CI, 3.0–9.8) and the median overall survival (OS) was 10.2 months (95% CI, 7.2–12.8). The biochemical response translated into a significantly prolonged PFS (12.9 vs. 2.8 mo, p &lt, 0.001) and OS (13.5 vs. 6.7 mo, p &lt, 0.001). Patients with PR on interim imaging after two cycles had a longer median OS compared to patients with stable or progressive disease (15.5 vs. 7.1 mo, p &lt, 0.001). Previous taxane-based chemotherapy (HR 3.21, 95%CI 1.18–8.70, p = 0.02) and baseline LDH levels (HR 1.001, 95%CI 1.000–1.001, p = 0.04) were inversely associated with OS on a Cox-regression analysis. Grade ≥ 3 hematological decline was observed after 22/201 (11%) cycles with anemia, leukopenia and thrombocytopenia in 15/45 (33%), 6/45 (13%) and 8/45 (18%) patients, respectively. Cumulative treatment activity and absorbed whole-body dose were not correlated with new onset grade ≥ 3 hematotoxicity (p = 0.91, p = 0.69). No event of grade ≥ 3 chronic kidney disease was observed during RLT or the follow-up. Last line RLT with 177Lu-PSMA-617 in mCRPC patients with diffuse bone marrow involvement may thus contribute to prolonged disease control at an acceptable safety profile.

Background: To evaluate the impact of time to castration resistance (TTCR) in metastatic hormone-sensitive prostate cancer (mHSPC) patients on overall survival (OS) in the era of combination therapies for mHSPC. Material and Methods: Of 213 mHSPC patients diagnosed between 01/2013-12/2020 who subsequently developed metastatic castration resistant prostate cancer (mCRPC), 204 eligible patients were analyzed after having applied exclusion criteria. mHSPC patients were classified into TTCR 24 months and analyzed regarding OS. Moreover, further OS analyses were performed after having developed mCRPC status according to TTCR. Logistic regression models predicted the value of TTCR on OS. Results: Median follow-up was 34 months. Among 204 mHSPC patients, 41.2% harbored TTCR 24 months. Median age was 67 years and median PSA at prostate cancer diagnosis was 61 ng/ml. No differences in patient characteristics were observed (all p>0.05). According to OS, TTCR 24 months, in that order (p24 months (all p0.05). Conclusion: Patients with TTCR

Objective: To investigate temporal trends in prostate cancer (PCa) radical prostatectomy (RP) candidates. Materials and Methods: Patients who underwent RP for PCa between January 2014 and December 2019 were identified form our institutional database. Trend analysis and logistic regression models assessed RP trends after stratification of PCa patients according to D'Amico classification and Gleason score. Patients with neoadjuvant androgen deprivation or radiotherapy prior to RP were excluded from the analysis. Results: Overall, 528 PCa patients that underwent RP were identified. Temporal trend analysis revealed a significant decrease in low-risk PCa patients from 17 to 9% (EAPC: −14.6%, p < 0.05) and GS6 PCa patients from 30 to 14% (EAPC: −17.6%, p < 0.01). This remained significant even after multivariable adjustment [low-risk PCa: (OR): 0.85, p < 0.05 and GS6 PCa: (OR): 0.79, p < 0.001]. Furthermore, a trend toward a higher proportion of intermediate-risk PCa undergoing RP was recorded. Conclusion: Our results confirm that inverse stage migration represents an ongoing phenomenon in a contemporary RP cohort in a European tertiary care PCa center. Our results demonstrate a significant decrease in the proportion of low-risk and GS6 PCa undergoing RP and a trend toward a higher proportion of intermediate-risk PCa patients undergoing RP. This indicates a more precise patient selection when it comes to selecting suitable candidates for definite surgical treatment with RP.

Objective: To investigate the value of standard [digital rectal examination (DRE), PSA] and advanced (mpMRI, prostate biopsy) clinical evaluation for prostate cancer (PCa) detection in contemporary patients with clinical bladder outlet obstruction (BOO) scheduled for Holmium laser enucleation of the prostate (HoLEP). Material and Methods: We retrospectively analyzed 397 patients, who were referred to our tertiary care laser center for HoLEP due to BOO between 11/2017 and 07/2020. Of those, 83 (20.7%) underwent further advanced clinical PCa evaluation with mpMRI and/or prostate biopsy due to elevated PSA and/or lowered PSA ratio and/or suspicious DRE. Logistic regression and binary regression tree models were applied to identify PCa in BOO patients. Results: An mpMRI was conducted in 56 (66%) of 83 patients and revealed PIRADS 4/5 lesions in 14 (25%) patients. Subsequently, a combined systematic randomized and MRI-fusion biopsy was performed in 19 (23%) patients and revealed in PCa detection in four patients (5%). A randomized prostate biopsy was performed in 31 (37%) patients and revealed in PCa detection in three patients (4%). All seven patients (9%) with PCa detection underwent radical prostatectomy with 29% exhibiting non-organ confined disease. Incidental PCa after HoLEP (n = 76) was found in nine patients (12%) with advanced clinical PCa evaluation preoperatively. In univariable logistic regression analyses, PSA, fPSA ratio, and PSA density failed to identify patients with PCa detection. Conversely, patients with a lower International Prostate Symptom Score (IPSS) and PIRADs 4/5 lesion in mpMRI were at higher risk for PCa detection. In multivariable adjusted analyses, PIRADS 4/5 lesions were confirmed as an independent risk factor (OR 9.91, p = 0.04), while IPSS did not reach significance (p = 0.052). Conclusion: In advanced clinical PCa evaluation mpMRI should be considered in patients with elevated total PSA or low fPSA ratio scheduled for BOO treatment with HoLEP. Patients with low IPSS or PIRADS 4/5 lesions in mpMRI are at highest risk for PCa detection. In patients with a history of two or more sets of negative prostate biopsies, advanced clinical PCa evaluation might be omitted.

Additional file 1: Fig. S1 Maximum intensity projections of 68 Ga-PMSA imaging at baseline: (a) 81-year-old patient (P8 in Table 3) with limited extent of bone metastases (category 1), the patient developed reversible grade 3 anemia after RLT. (b) 75-year-old patient (P 13 in Table 3) with diffuse bone marrow involvement (category 2), developing progressive disease and irreversible hematological decline with grade 3 anemia and grade 4 thrombocytopenia after 6 cycles of RLT.

Background: Since January 2018 performance of urethroplasties is done on regular basis at the University Hospital Frankfurt (UKF). We aimed to implement and transfer an institutional standardized perioperative algorithm for urethral surgery (established at the University Hospital Hamburg-Eppendorf—UKE) using a validated Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) in patients undergoing urethroplasty at UKF.Materials and Methods: We retrospectively analyzed all patients who underwent urethroplasty for urethral stricture disease between January 2018 and January 2020 at UKF. All patients were offered to revisit for clinical follow-up (FU) and completion of USS-PROM. Primary end point was stricture recurrence-free survival (RFS). Secondary endpoints were functional outcomes, quality of life (QoL), and patient satisfaction.Results: In total, 50 patients underwent urethroplasty and 74 and 24% had a history of previous urethrotomy or urethroplasty, respectively. A buccal mucosal graft urethroplasty was performed in 86% (n = 43). After patient's exclusion due to lost of FU, FU

Prostate cancer patients whose tumors develop resistance to conventional treatment often turn to natural, plant-derived products, one of which is sulforaphane (SFN). This study was designed to determine whether anti-tumor properties of SFN, identified in other tumor entities, are also evident in cultivated DU145 and PC3 prostate cancer cells. The cells were incubated with SFN (1&ndash, 20 &micro, M) and tumor cell growth and proliferative activity were evaluated. Having found a considerable anti-growth, anti-proliferative, and anti-clonogenic influence of SFN on both prostate cancer cell lines, further investigation into possible mechanisms of action were performed by evaluating the cell cycle phases and cell-cycle-regulating proteins. SFN induced a cell cycle arrest at the S- and G2/M-phase in both DU145 and PC3 cells. Elevation of histone H3 and H4 acetylation was also evident in both cell lines following SFN exposure. However, alterations occurring in the Cdk-cyclin axis, modification of the p19 and p27 proteins and changes in CD44v4, v5, and v7 expression because of SFN exposure differed in the two cell lines. SFN, therefore, does exert anti-tumor properties on these two prostate cancer cell lines by histone acetylation and altering the intracellular signaling cascade, but not through the same molecular mechanisms.

Objective: Many patients with localized prostate cancer (PCa) do not immediately undergo radical prostatectomy (RP) after biopsy confirmation. The aim of this study was to investigate the influence of “time-from-biopsy-to- prostatectomy” on adverse pathological outcomes. Materials and Methods: Between January 2014 and December 2019, 437 patients with intermediate- and high risk PCa who underwent RP were retrospectively identified within our prospective institutional database. For the aim of our study, we focused on patients with intermediate- (n = 285) and high-risk (n = 151) PCa using D'Amico risk stratification. Endpoints were adverse pathological outcomes and proportion of nerve-sparing procedures after RP stratified by “time-from-biopsy-to-prostatectomy”: ≤3 months vs. >3 and < 6 months. Medians and interquartile ranges (IQR) were reported for continuously coded variables. The chi-square test examined the statistical significance of the differences in proportions while the Kruskal-Wallis test was used to examine differences in medians. Multivariable (ordered) logistic regressions, analyzing the impact of time between diagnosis and prostatectomy, were separately run for all relevant outcome variables (ISUP specimen, margin status, pathological stage, pathological nodal status, LVI, perineural invasion, nerve-sparing). Results: We observed no difference between patients undergoing RP ≤3 months vs. >3 and 3 and 3 months did not significantly worsen any of the outcome variables in patients with intermediate- or high-risk PCa (all p > 0.05). Conclusion: A “time-from-biopsy-to-prostatectomy” of >3 and

Chronic treatment with the mTOR inhibitor, everolimus, fails long-term in preventing tumor growth and dissemination in cancer patients. Thus, patients experiencing treatment resistance seek complementary measures, hoping to improve therapeutic efficacy. This study investigated metastatic characteristics of bladder carcinoma cells exposed to everolimus combined with the isothiocyanate sulforaphane (SFN), which has been shown to exert cancer inhibiting properties. RT112, UMUC3, or TCCSUP bladder carcinoma cells were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5 &micro, M), alone or in combination. Adhesion and chemotaxis along with profiling details of CD44 receptor variants (v) and integrin &alpha, and &beta, subtypes were evaluated. The functional impact of CD44 and integrins was explored by blocking studies and siRNA knock-down. Long-term exposure to everolimus enhanced chemotactic activity, whereas long-term exposure to SFN or the SFN-everolimus combination diminished chemotaxis. CD44v4 and v7 increased on RT112 cells following exposure to SFN or SFN-everolimus. Up-regulation of the integrins &alpha, 6, &alpha, V, and &beta, 1 and down-regulation of &beta, 4 that was present with everolimus alone could be prevented by combining SFN and everolimus. Down-regulation of &alpha, V, &beta, 1, and &beta, 4 reduced chemotactic activity, whereas knock-down of CD44 correlated with enhanced chemotaxis. SFN could, therefore, inhibit resistance-related tumor dissemination during everolimus-based bladder cancer treatment.

Progressive bladder cancer growth is associated with abnormal activation of the mammalian target of the rapamycin (mTOR) pathway, but treatment with an mTOR inhibitor has not been as effective as expected. Rather, resistance develops under chronic drug use, prompting many patients to lower their relapse risk by turning to natural, plant-derived products. The present study was designed to evaluate whether the natural compound, sulforaphane (SFN), combined with the mTOR inhibitor everolimus, could block the growth and proliferation of bladder cancer cells in the short- and long-term. The bladder cancer cell lines RT112, UMUC3, and TCCSUP were exposed short- (24 h) or long-term (8 weeks) to everolimus (0.5 nM) or SFN (2.5 &micro, M) alone or in combination. Cell growth, proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins were evaluated. siRNA blockade was used to investigate the functional impact of the proteins. Short-term application of SFN and/or everolimus resulted in significant tumor growth suppression, with additive inhibition on clonogenic tumor growth. Long-term everolimus treatment resulted in resistance development characterized by continued growth, and was associated with elevated Akt-mTOR signaling and cyclin-dependent kinase (CDK)1 phosphorylation and down-regulation of p19 and p27. In contrast, SFN alone or SFN+everolimus reduced cell growth and proliferation. Akt and Rictor signaling remained low, and p19 and p27 expressions were high under combined drug treatment. Long-term exposure to SFN+everolimus also induced acetylation of the H3 and H4 histones. Phosphorylation of CDK1 was diminished, whereby down-regulation of CDK1 and its binding partner, Cyclin B, inhibited tumor growth. In conclusion, the addition of SFN to the long-term everolimus application inhibits resistance development in bladder cancer cells in vitro. Therefore, sulforaphane may hold potential for treating bladder carcinoma in patients with resistance to an mTOR inhibitor.

Background: Although mechanistic target of rapamycin (mTOR) inhibitors, such as temsirolimus, show promise in treating bladder cancer, acquired resistance often hampers efficacy. This study evaluates mechanisms leading to resistance. Methods: Cell growth, proliferation, cell cycle phases, and cell cycle regulating proteins were compared in temsirolimus resistant (res) and sensitive (parental&mdash, par) RT112 and UMUC3 bladder cancer cells. To evaluate invasive behavior, adhesion to vascular endothelium or to immobilized extracellular matrix proteins and chemotactic activity were examined. Integrin &alpha, and &beta, subtypes were analyzed and blocking was done to evaluate physiologic integrin relevance. Results: Growth of RT112res could no longer be restrained by temsirolimus and was even enhanced in UMUC3res, accompanied by accumulation in the S- and G2/M-phase. Proteins of the cdk-cyclin and Akt-mTOR axis increased, whereas p19, p27, p53, and p73 decreased in resistant cells treated with low-dosed temsirolimus. Chemotactic activity of RT112res/UMUC3res was elevated following temsirolimus re-exposure, along with significant integrin &alpha, 2, &alpha, 3, and &beta, 1 alterations. Blocking revealed a functional switch of the integrins, driving the resistant cells from being adhesive to being highly motile. Conclusion: Temsirolimus resistance is associated with reactivation of bladder cancer growth and invasive behavior. The &alpha, 1 integrins could be attractive treatment targets to hinder temsirolimus resistance.

This study was designed to investigate whether epigenetic modulation by histone deacetylase (HDAC) inhibition might circumvent resistance towards the mechanistic target of rapamycin (mTOR) inhibitor temsirolimus in a prostate cancer cell model. Parental (par) and temsirolimus-resistant (res) PC3 prostate cancer cells were exposed to the HDAC inhibitor valproic acid (VPA), and tumor cell adhesion, chemotaxis, migration, and invasion were evaluated. Temsirolimus resistance was characterized by reduced binding of PC3res cells to endothelium, immobilized collagen, and fibronectin, but increased adhesion to laminin, as compared to the parental cells. Chemotaxis, migration, and invasion of PC3res cells were enhanced following temsirolimus re-treatment. Integrin &alpha, and &beta, receptors were significantly altered in PC3res compared to PC3par cells. VPA significantly counteracted temsirolimus resistance by down-regulating tumor cell&ndash, matrix interaction, chemotaxis, and migration. Evaluation of integrin expression in the presence of VPA revealed a significant down-regulation of integrin &alpha, 5 in PC3res cells. Blocking studies demonstrated a close association between &alpha, 5 expression on PC3res and chemotaxis. In this in vitro model, temsirolimus resistance drove prostate cancer cells to become highly motile, while HDAC inhibition reversed the metastatic activity. The VPA-induced inhibition of metastatic activity was accompanied by a lowered integrin &alpha, 5 surface level on the tumor cells.

Einleitung: Die akute bakterielle Epididymitis ist eine häufige Erkrankung, die mit einer aszendierenden Infektion der Urethra oder einer deszendierenden Infektion der Harnblase assoziiert ist. Material und Methoden: Daten von 287 Patienten mit akuter Epididymitis, die sich zwischen Januar[zum vollständigen Text gelangen Sie über die oben angegebene URL], 59. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V. - Urologie im Südwesten: Innovation aus Tradition

Einleitung: Patienten mit hohen präoperativen PSA-Werten können zum Zeitpunkt einer radikalen Prostatektomie unentdeckte Metastasen haben, was mit einem schlechteren Outcome verbunden sein kann. Material und Methoden: 466 Patienten mit einem klinisch lokalisierten Prostatakarzinom, einem[zum vollständigen Text gelangen Sie über die oben angegebene URL], 59. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V. - Urologie im Südwesten: Innovation aus Tradition

Einleitung: Curcumin ist ein aus der Gelbwurzel gewonnenes Phytopharmakon mit immunmodulatorischen und anti-proliferativen Eigenschaften, jedoch mit unbefriedigender Bioverfügbarkeit. Ziel der Studie war es zu evaluieren, ob sich die antitumorale Wirkung von Curcumin auf Zellen des Blasenkarzinoms[zum vollständigen Text gelangen Sie über die oben angegebene URL], 59. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V. - Urologie im Südwesten: Innovation aus Tradition

Einleitung: 80% der Patienten beschreiben nach Einlage von Harnleiterschienen Flankenschmerz, Miktionsbeschwerden und Makrohämaturie. Die Genese dieser Beschwerden ist multifaktoriell. Hierbei spielen sowohl Positionierung der Harnleiterschienen als auch deren Durchmesser und das Material [zum vollständigen Text gelangen Sie über die oben angegebene URL], 59. Jahrestagung der Südwestdeutschen Gesellschaft für Urologie e.V. - Urologie im Südwesten: Innovation aus Tradition

BACKGROUND Intermediate-risk prostate cancer (PCa) represents a heterogeneous disease, where a non-negligible proportion of patients harbor favorable pathologic characteristics and are potentially eligible for active surveillance (AS). We aimed at developing a model for the identification of pathologically favorable PCa at radical prostatectomy (RP) among intermediate-risk patients. METHODS Overall, 3,821 intermediate-risk patients treated with RP at two centers between 2005 and 2013 were identified. Pathologically favorable PCa was defined as low-grade organ-confined disease. Age, biopsy Gleason, PSA density (PSAD), and the percentage of positive cores were included in multivariable logistic regression analyses predicting favorable PCa and formed the basis for a logistic regression-based risk calculator. The internally validated discrimination and calibration of the risk calculator were quantified using 200 bootstrap resamples. Decision curve analysis (DCA) provided an estimate of the net benefit obtained using this model versus treating no one and treating everyone. RESULTS Overall, 10.0% of all intermediate risk patients had favorable disease. In multivariable analyses, patients with biopsy Gleason score ≤6 had higher probability of favorable disease compared to those with higher-grade disease (P

Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP). We relied on the Surveillance, Epidemiology and End Results 2004–2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4–5) at RP. Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p

Background and objectives: to test for differences in perioperative outcomes and total hospital costs (THC) in nonmetastatic bladder cancer patients undergoing open (ORC) versus robotic-assisted radical cystectomy (RARC). Methods: we relied on the National Inpatient Sample database (2016-2019). Statistics consisted of trend analyses, multivariable logistic, Poisson, and linear regression models. Results Of 5280 patients, 1876 (36%) versus 3200 (60%) underwent RARC versus ORC. RARC increased from 32% to 41% (estimated annual percentage change [EAPC]: + 8.6%; p = 0.02). Rates of transfusion (8% vs. 16%), intraoperative (2% vs. 3%), wound (6% vs. 10%), and pulmonary (6% vs. 10%) complications were lower in RARC patients (all p < 0.05). Moreover, median length of stay (LOS) was shorter in RARC (6 vs. 7days; p < 0.001). Conversely, median THC (31,486 vs. 27,162$; p < 0.001) were higher in RARC. Multivariable logistic regression-derived odds ratios addressing transfusion (0.49), intraoperative (0.53), wound (0.68), and pulmonary (0.71) complications favored RARC (all p < 0.01). In multivariable Poisson and linear regression models, RARC was associated with shorter LOS (Rate ratio:0.86; p < 0.001), yet higher THC (Coef.:5,859$; p < 0.001). RARC in-hospital mortality was lower (1% vs. 2%; p = 0.04). Conclusions: RARC complications, LOS, and mortality appear more favorable than ORC, but result in higher THC. The favorable RARC profile contributes to its increasing popularity throughout the United States., B.H. was awarded a scholarship by the STIFTUNG GIERSCH. OpenAccess funding enabled and organized by Projekt DEAL.

Background Prostate cancer (PCa) staging is crucial in clinical decision making and treatment assignment. Objective To develop a predictive tool that is capable of predicting the probability of metastases at initial PCa diagnosis. Design, setting, and participants Within the Surveillance, Epidemiology, and End Results database (2010–2014), we identified patients with newly diagnosed PCa and available clinical tumor stage, prostatic-specific antigen value (PSA), and Gleason grade group (GGG), and with or without metastases. Outcome measurements and statistical analysis We relied on PSA, clinical tumor stages, and GGG to discriminate between M1 and M0 patients. Patients were randomly divided according to the registry of origin between development (n = 102 469) and validation (n = 98 755) cohorts. Logistic regression modeling coefficients were used to devise a lookup table to discriminate between M0 and M1 stages. Receiver operating characteristic-derived area under the curve was tested for model accuracy, within the validation cohort. A total of 2000 bootstrap resamples were applied to 95% confidence intervals (CIs). Decision curve analysis (DCA) and calibration plots were used to test the performance of the lookup table. Results and limitations Of 201 224 patients, 3.5% harbored metastatic PCa (mPCa). PSA >40 ng/ml, GGG5, and GGG4, in that order, represented the strongest predictors of mPCa. Overall, PSA, clinical tumor stage, and GGG were 94.3% (95% CI: 94.2–94.3%) accurate in predicting the probability of mPCa, in the external validation cohort. Up to 39.4% probability of mPCa, the model demonstrated accurate predictions in the calibration plot. In DCA, a net benefit was recorded up to a threshold probability of approximately 54%. Conclusions The proposed lookup table for the prediction of the probability of mPCa may represent a useful clinical tool based on its high accuracy, excellent calibration, and robust nature of predictions. Patient summary Our study provides a highly accurate lookup table for the prediction of the probability of metastatic prostate cancer patients. This clinical tool can be useful in staging decisions.

Background: no North-American study tested the survival benefit of chemotherapy in de novo metastatic prostate cancer according to race/ethnicity. We addressed this void. Methods: we identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results database (2014–2015). Separate and specific Kaplan–Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed versus chemotherapy-naïve patients in four race/ethnicity groups: Caucasian versus African-American versus Hispanic/Latino vs Asian. Race/ethnicity specific propensity score matching was applied. Here, additional landmark analysis was performed. Results: of 4232 de novo metastatic prostate cancer patients, 2690 (63.3%) were Caucasian versus 783 (18.5%) African-American versus 504 (11.8%) Hispanic/Latino versus 257 (6.1%) Asian. Chemotherapy rates were: 21.3% versus 20.8% versus 21.0% versus 20.2% for Caucasians versus African-Americans versus Hispanic/Latinos versus Asians, respectively. At 30 months of follow-up, overall survival rates between chemotherapy-exposed versus chemotherapy-naïve patients were 61.5 versus 53.2% (multivariable hazard ratio [mHR]: 0.76, 95 confidence interval [CI]: 0.63–0.92, p = 0.004) in Caucasians, 55.2 versus 51.6% (mHR: 0.76, 95 CI: 0.54–1.07, p = 0.11) in African-Americans, 62.8 versus 57.0% (mHR: 1.11, 95 CI: 0.73–1.71, p = 0.61) in Hispanic/Latinos and 77.7 versus 65.0% (mHR: 0.31, 95 CI: 0.11–0.89, p = 0.03) in Asians. Virtually the same findings were recorded after propensity score matching within each race/ethnicity group. Conclusions: caucasian and Asian de novo metastatic prostate cancer patients exhibit the greatest overall survival benefit from chemotherapy exposure. Conversely, no overall survival benefit from chemotherapy exposure could be identified in either African-Americans or Hispanic/Latinos. Further studies are clearly needed to address these race/ethnicity specific disparities., Giersch Stiftung; Projekt DEAL

Context: meticulous knowledge about the anatomy of the prostate and surrounding tissue represents a crucial and mandatory requirement during radical prostatectomy for reliable oncological and excellent replicable, functional outcomes. Since its introduction two decades ago, robotic-assisted laparoscopic radical prostatectomy (RALP) has evolved to become the predominant surgical approach in many industrialized countries. Objective: to provide and highlight currently available literature regarding prostate anatomy and to help in improving oncological and functional outcomes in RALP. Methods/Evidence Acquiring: PubMed database was searched using the following keywords: “robotic-assisted radical prostatectomy,” “anatomy,” “neurovascular bundle,” “nerve,” “periprostatic fascia,” “pelvis,” “sphincter,” “urethra,” “urinary incontinence,” and “erectile dysfunction.” Relevant articles and book chapters were critically reviewed and if eligible, they were included in this review. Results: new evidence in regards to prostatic anatomy and surgical approaches in RALP has been reported in recent years. Besides detailed anatomical studies investigating the meticulous structure of the fascial structures surrounding the prostate and neurovascular bundle preservation, debate about the optimal RALP approach is still ongoing, inspired by recent publications presenting promising functional outcomes following modifications in surgical approaches. Conclusions: this review provides a detailed overview of the current knowledge of prostate anatomy, its surrounding tissue, and its influence on key surgical step development for RALP., Stiftung Giersch

Background: the pathological stage of prostate cancer with high-risk prostate-specific antigen (PSA) levels, but otherwise favorable and/or intermediate risk characteristics (clinical T-stage, Gleason Grade group at biopsy [B-GGG]) is unknown. We hypothesized that a considerable proportion of such patients will exhibit clinically meaningful GGG upgrading or non-organ confined (NOC) stage at radical prostatectomy (RP). Materials and methods: within the Surveillance, Epidemiology, and End Results: database (2010-2015) we identified RP-patients with cT1c-stage and B-GGG1, B-GGG2, or B-GGG3 and PSA 20-50 ng/ml. Rates of GGG4 or GGG5 and/or rates of NOC stage (>= pT3 and/or pN1) were analyzed. Subsequently, separate univariable and multivariable logistic regression models tested for predictors of NOC stage and upgrading at RP. Results Of 486 assessable patients, 134 (28%) exhibited B-GGG1, 209 (43%) B-GGG2, and 143 (29%) B-GGG3, respectively. The overall upgrading and NOC rates were 11% and 51% for a combined rate of upgrading and/or NOC stage of 53%. In multivariable logistic regression models predicting upgrading, only B-GGG3 was an independent predictor (odds ratio [OR]: 5.29; 95% confidence interval [CI]: 2.21-14.19; p < 0.001). Conversely, 33%-66% (OR: 2.36; 95% CI: 1.42-3.95; p = 0.001) and >66% of positive biopsy cores (OR: 4.85; 95% CI: 2.84-8.42; p < 0.001), as well as B-GGG2 and B-GGG3 were independent predictors for NOC stage (all p, Stiftung Giersch; Projekt DEAL

Salvage radiotherapy improves oncologic outcomes in prostate cancer patients who develop biochemical recurrence after radical prostatectomy. However, the evidence on hard clinical endpoints is scarce. Within this study, we compare the long-term oncologic outcomes of patients with biochemical recurrence after prostatectomy, who were treated with either salvage radiotherapy or no radiotherapy. Our results show that patients who were treated with salvage radiotherapy after the development of biochemical recurrence following radical prostatectomy had a lower risk of developing metastasis and lower risk of death within the follow-up. These findings further underline the curative potential of salvage radiotherapy in the case of biochemical recurrence after radical prostatectomy, and should be discussed with these patients. Background: Salvage radiotherapy (SRT) improves oncologic outcomes in prostate cancer (PCa) patients who develop biochemical recurrence (BCR) after radical prostatectomy (RP). However, evidence on hard clinical endpoints is scarce. We compare long-term oncologic outcomes of SRT versus no radiotherapy (noRT) in patients with BCR after RP. Patients and methods: within a multi-institutional database, we identified patients with BCR after RP between 1989 and 2016 for PCa. Patients with lymph node invasion, with adjuvant radiotherapy, or with additional androgen deprivation therapy at BCR were excluded. In all patients with SRT, SRT was delivered to the prostatic bed only. Propensity score matching (PSM) was performed to account for differences in pathologic tumor characteristics. Kaplan-Meier analyses and Cox regression models tested the effect of SRT versus no RT on metastasis-free (MFS) and overall survival (OS). Results: of 1832 patients with BCR, 32.9% (n = 603) received SRT without ADT. The median follow-up was 95.9 months. Median total SRT dose was 70.2 Gy. After 1:1 PSM, at 15 years after RP, MFS and OS rates were 84.3 versus 76.9% (p < 0.001) and 85.3 versus 74.4% (p = 0.04) for SRT and noRT, respectively. In multivariable Cox regression models, SRT was an independent predictor for metastasis (HR: 0.37, p < 0.001) and OS (HR: 0.64, p = 0.03). Conclusion: this is the first matched-pair analysis investigating the impact of SRT versus observation only in post-RP recurrent PCa. After compensating for established risk factors, SRT was associated with better long-term MFS and OS. These results on clinical endpoints underline the curative potential of SRT., NA

The objective of the study was to test the impact of implementing standard full functional-length urethral sphincter (FFLU) and neurovascular bundle preservation (NVBP) with intraoperative frozen section technique (IFT) on long-term urinary continence in patients undergoing robotic-assisted radical prostatectomy (RARP). We relied on an institutional tertiary-care database to identify patients who underwent RARP between 01/2014 and 09/2019. Until 10/2017, FFLU was not performed and decision for NVBP was taken without IFT. From 11/2017, FFLU and IFT-guided NVBP was routinely performed in all patients undergoing RARP. Long-term continence (>= 12 months) was defined as the usage of no or one safety- pad. Uni- and multivariable logistic regression models tested the correlation between surgical approach (standard vs FFLU + NVBP) and long-term continence. Covariates consisted of age, body mass index, prostate volume and extraprostatic extension of tumor. The study cohort consisted of 142 patients, with equally sized groups for standard vs FFLU + NVBP RARP (68 vs 74 patients). Routine FFLU + NVBP implementation resulted in a long-term continence rate of 91%, compared to 63% in standard RARP (p < 0.001). Following FFLU + NVBP RARP, 5% needed 1-2, 4% 3-5 pads/24 h and no patient (0%) suffered severe long-term incontinence (> 5 pads/24 h). No significant differences in patient or tumor characteristics were recorded between both groups. In multivariable logistic regression models, FFLU + NVBP was a robust predictor for continence (Odds ratio [OR]: 7.62; 95% CI 2.51-27.36; p < 0.001). Implementation of FFLU and NVBP in patients undergoing RARP results in improved long-term continence rates of 91%., Stiftung Giersch; Projekt DEAL

Background Nodal metastasis is the strongest risk factor of disease recurrence in patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP). Objective To develop a model that allows quantification of the likelihood that a pathologically node-negative patient is indeed free of nodal metastasis. Design, setting, and participants Data from patients treated with RP and pelvic lymph node dissection (PLND; n = 7135) for PCa between 2000 and 2011 were analyzed. For external validation, we used data from patients (n = 4209) who underwent an anatomically defined extended PLND. Intervention RP and PLND. Outcome measurements and statistical analysis We developed a novel pathologic (postoperative) nodal staging score (pNSS) that represents the probability that a patient is correctly staged as node negative based on the number of examined nodes and the patient's characteristics. Results and limitations In the development and validation cohorts, the probability of missing a positive node decreases with an increasing number of nodes examined. Whereas in pT2 patients, a 90% pNSS was achieved with one single examined node in both the development and validation cohort, a similar level of nodal staging accuracy was achieved in pT3a patients by examining five and nine nodes, respectively. The pT3b/T4 patients achieved a pNSS of 80% and 70% when 17 and 20 nodes in the development and validation cohort were examined, respectively. This study is limited by its retrospective design and multicenter nature. The number of nodes removed was not directly correlated with the extent/template of PLND. Conclusions Every patient needs PLND for accurate nodal staging. However, a one-size-fits-all approach is too inaccurate. We developed a tool that indicates a node-negative patient is indeed free of lymph node metastasis by evaluating the number of examined nodes, pT stage, RP Gleason score, surgical margins, and prostate-specific antigen. This tool may help in postoperative decision making. © 2013 European Association of Urology.

Background: The rate of insignificant prostate cancer (IPCa) is increasing. Objectives: To examine three end points in patients with a single, positive core and no high-grade prostate cancer (PCa) at biopsy, namely (1) rate of clinical IPCa at radical prostatectomy (RP), defined as organ-confined PCa with a Gleason score of 6 or lower and tumor volume < 0.5 cc; (2) rate of pathologically unfavorable PCa at RP (Gleason 7-10 or non-organ-confined disease); and (3) ability to predict either insignificant or unfavorable PCa at RP. Design, Setting, and Participants: Retrospective analysis of 209 men with one positive biopsy core showing Gleason 6 or lower. Measurements: : Detailed clinical and RP data were used in multivariable logistic regression models. Their bias-corrected accuracy estimates were quantified using the area under the curve (AUC) method. Results and Limitations: At RP, IPCa was present in 28 patients (13.4%) and pathologically unfavorable PCa, defined as Gleason 7 or higher or non-organ-confined PCa, was reported in 70 (33.5%) of 209 men; when Gleason 8 or higher or non-organ-confined PCa was considered, the proportion fell to 11%. Our multivariable models predicting different categories of pathologically unfavorable PCa at RP had an accuracy rate between 56% and 68% for predicting IPCa at RP versus 65.1% to 66.1% and 61.7% for the IPCa nomograms of Kattan et al and Nakanishi et al, respectively. Our data are not applicable to screening because they originate from a referral population. Conclusions: Despite highly favorable biopsy features, between 11% and 33% of men had unfavorable PCa at RP and only a minority (13.4%) had pathologically confirmed IPCa. Neither clinically insignificant nor pathologically unfavorable features could be predicted with sufficient accuracy for clinical decision making. (C) 2008 European Association of Urology. Published by Elsevier B.V. All rights reserved.

BACKGROUND. Active surveillance (AS) represents a treatment option for select patients with low-risk, organ-confined prostate cancer (PCa). In this report, the authors addressed the rates of misclassification associated with the use of 5 different clinical criteria for AS. Misclassification was defined as the presence of either nonorgan-confined disease or high-grade PCa. METHODS. Between 1992 and 2007, 4885 patients underwent radical prostatectomy (RP) at 1 of 2 European academic centers, and the patients were identified who fulfilled the criteria for AS according to 5 different investigational groups (Hardie et al, Roemeling et al, Choo et al, Klotz, and D'Amico and Coleman). Statistics targeted the rates of misclassification for each of the 5 definitions. RESULTS. Four thousand three hundred eight patients, 4047 patients, 3993 patients, 2455 patients, and 2345 patients fulfilled the AS criteria of Hardie et al, Roemeling et al, Choo et al, Klotz, and D'Amico and Coleman, respectively. Extracapsular extension was reported in 13.5% to 26% of patients, and seminal vesicle invasion was reported in 2.9% to 8.2% of patients. When PCa with Gleason scores from 8 to 10 at RP was considered high grade, the misclassification rates were 27%, 25%, 25%, 15%, and 14% for the 5 studies, respectively. Conversely, when PCa with Gleason scores from 7 to 10 was considered high grade, the misclassification rates increased to 56%, 55%, 45%, 42%, and 39%, respectively. CONCLUSIONS. The currently available AS criteria are limited by a high rate of misclassification. The use of more selective AS criteria may reduce the rate of misclassification but also may reduce significantly the percentage of patients who may be considered for AS. Cancer 2008. © 2008 American Cancer Society.

Purpose: A recent prostate cancer finasteride chemoprevention trial showed a higher rate of sextant biopsy-detected high grade prostate cancer (HGPCa) in finasteride exposed men, whose prostates were significantly smaller than those of controls. We investigated the association between prostate size and prostate cancer grade and stage in a large (n = 3412) single center radical prostatectomy cohort, which was unexposed to any form of hormonal manipulation. Methods: Logistic regression models were used. Results: Small prostates were associated with higher rate of HGPCa at biopsy and at radical prostatectomy (both p < 0.001), with higher rate of extracapsular extension (p < 0.001), seminal vesicle invasion (p < 0.001) and with tumor volume > 3.4cc, after accounting for age, PSA, clinical stage and year of surgery. Conclusions: Our findings demonstrate that prostate cancers located in small glands are fundamentally more aggressive than those located within larger glands. in consequence, prostate cancer detection and treatment strategies should account for prostate volume. (c) 2007 Elsevier Ltd. All rights reserved.

Objectives: To determine if the number of lymph nodes (LNs) removed is an independent predictor of biochemical recurrence (BCR) in patients without LN metastases undergoing radical prostatectomy (RP). Material and methods: Retrospective analysis of 7,310 patients treated at 7 centers with RP and pelvic LN dissection for clinically localized prostate cancer between 2000 and 2011. Patients with LN metastases (n = 398) and other reasons (stated later in the article) (n = 372) were excluded, which left 6,540 patients for the final analyses. Results: Overall, median biopsy and RP Gleason score were both 7; median prostate specific antigen level was 6. ng/ml (interquartile range [IQR]: 5); and median number of LNs removed was 6 (IQR: 8). A total of 3,698 (57%), 2,064 (32%), and 508 (8%) patients had ≥6, ≥10, and ≥20 LNs removed, respectively. Patients with more LNs removed were older, had a higher prostate specific antigen level, had higher clinical and pathologic T stage, and had higher RP Gleason score (all P

Objective To determine the association between peri-operative blood transfusion (PBT) and oncological outcomes in a large multi-institutional cohort of patients undergoing radical cystectomy (RC) for urothelial carcinoma of the bladder (UCB). Patients and Methods We conducted a retrospective analysis of 2895 patients treated with RC for UCB. Univariable and multivariable Cox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer-specific mortality, and any-cause mortality. Results Patients' median (interquartile range [IQR]) age was 67 (60, 73) years and the median (IQR) follow-up was 36.1 (15, 84) months. Patients who received PBT were more likely to have advanced disease (P < 0.001), high grade tumours (P = 0.047) and nodal metastasis (P = 0.004). PBT was associated with a higher risk of disease recurrence (P = 0.003), cancer-specific mortality (P = 0.017), and any-cause mortality (P = 0.010) in univariable, but not multivariable, analyses (P > 0.05). In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer-specific mortality and any-cause mortality (all P values

Purpose: A positive surgical margin after radical prostatectomy is considered an adverse prognostic feature. However, few groups have explored the potential interaction between surgical margin status and other cancer characteristics, specifically pathological stage. We addressed the first degree of interaction between positive surgical margins and other established adverse predictors of biochemical recurrence after radical prostatectomy. Materials and Methods: We used univariate and multivariate analysis to test the effect of surgical margin status on biochemical recurrence in 4,490 patients treated at a single institution between 1992 and 2008. We systematically tested all first-degree interactions between surgical margin status, and pretreatment prostate specific antigen, pT and pN stage, and radical prostatectomy Gleason sum. If interactions were significant, we quantified the effect on the biochemical recurrence rate. Results: Overall 850 patients (18.9%) had positive surgical margins. In those with negative vs positive surgical margins the 5-year biochemical recurrence-free survival rate was 95% vs 83%, 74% vs 62% and 47% vs 29% for pT2, pT3a and pT3b disease, respectively. In multivariate models only the pT stage-surgical margin status interaction achieved independent predictor status (p = 0.003). Negative vs positive surgical margin multivariate HRs were 1 vs 2.9, 2.3 vs 4.3 and 4.1 vs 5.6 in pT2, pT3a and pT3b cases, respectively. Conclusions: Compared to negative surgical margins, positive surgical margins increase the absolute biochemical recurrence 5-year rate by 12% to 18%. More importantly, positive surgical margins may substantially worsen the prognosis beyond that of the original pathological disease stage.

Context: The number and location of biopsy cores and the interpretation of prostate biopsy in different clinical settings remain the subjects of continuing debate. Objective: Our aim was to review the current evidence regarding the performance and interpretation of initial, repeat, and saturation prostatic biopsy. Evidence acquisition: A comprehensive Medline search was performed using the Medical Subject Heading search terms prostate biopsy, prostate cancer, detection, transrectal ultrasound (TRUS), nomogram, and diagnosis. Results were restricted to the English language, with preference given to those published within the last 3 yr. Evidence synthesis: At initial biopsy, a minimum of 10 but not > 18 systematic cores are recommended, with 14-18 cores in glands >= 50 cm(3). Biopsies should be directed laterally, and transition zone (TZ) cores are not recommended in the initial biopsy setting. Further biopsy sets, either as an extended repeat or as a saturation biopsy(>= 20 cores) including the TZ, are warranted in young and fit men with a persistent suspicion of prostate cancer. An immediate repeat biopsy is not indicated for prior high-grade prostatic intraepithelial neoplasia diagnosis given an adequate extended initial biopsy. Conversely, biopsies with atypical glands that are suspicious but not diagnostic of cancer should be repeated within 3-6 mo. Overall recommendations for further biopsy sets (a third set or more) cannot be made. Transrectal ultrasound-guided systematic biopsies represent the standard-of-care method of prostate sampling. However, transperineal biopsies are an up-to-standard alternative. Conclusions: The optimal prostatic biopsy regimen should be based on the individualized clinical setting of the patient and should follow the minimum standard requirements reported in this paper. (C) 2010 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Objective: To investigate the prostate cancer (PCa) prevalence and risk factors of men with prostate-specific antigen (PSA) level = 7. Results: Overall PCa detection rate was 23.1%. The majority had a biopsy Gleason sum of 6 (79.S%) and 20.5% had a biopsy Gleason sum >= 7. Total PSA (tPSA) and percentage of free PSA (%fPSA) were statistically significantly different in men with and without PCa (all p < 0.001). In tPSA strata < 0.5, 0.6-1.0, 1.1-2.0, 2.1-3.0, and 3.1-4.0 ng/ml, PCa prevalence was 4.0%, 10.6%, 14.8%, 24.5%, and 32.1%, respectively. in logistic regression analyses addressing PCa and Gleason sum >= 7 at biopsy, %fPSA and prostate volume represented independent and most informative risk factors. Conclusion: Our data demonstrate that a substantial percentage (23.1%) of men with a PSA < 4.0 ng/ml and an unsuspicious DRE in a biopsy referral population harbor PCa, with 20.5% being high grade. Low %fPSA and low prostate volume represent important parameters in PCa and in high grade disease detection at biopsy, respectively. (C) 2007 European Association of Urology. Published by Elsevier B.V. All rights reserved.