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Background: Multiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring., Objective: To assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%., Design Setting and Participants: PROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1-3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4-5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients., Outcome Measurements and Statistical Analysis: We calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables., Results and Limitations: The study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen ( p  < 0.001) and higher PRECISE score (4-5; p  = 0.005) were significant predictors of histological progression of GG 1 PC. Higher PRECISE score ( p  = 0.009), initial Prostate Imaging-Reporting and Data System score ( p  = 0.009), previous negative biopsy ( p  = 0.02), and percentage Gleason pattern 4 ( p  = 0.04) were significant predictors of histological progression of GG 2 PC. Limitations include extensive MRI reading experience, the small sample size, and limited follow-up., Conclusions: MRI-guided monitoring of patients on AS using PRECISE scores avoided unnecessary follow-up biopsies in 88% of patients with GG 1 PC and predicted upgrading during 2-yr follow-up in both GG 1 and GG 2 PC., Patient Summary: We investigated whether MRI (magnetic resonance imaging) scores can be used to guide whether patients with lower-risk prostate cancer who are on active surveillance (AS) need to undergo repeat biopsies. Follow-up biopsy was deferred for 1 year for patients with a stable score and performed for patients whose score progressed. After 24 months on AS, all men underwent MRI and biopsy. Among patients with grade group 1 cancer and a stable MRI score, 88% avoided biopsy. For patients with MRI score progression, AS termination was correctly recommended in 81% of grade group 1 and 92% of grade group 2 cases., (© 2023 Published by Elsevier B.V. on behalf of European Association of Urology.)

Background: To assess the diagnostic value of an additional late-phase PET/CT scan after urination as part of 68  Ga-PSMA-11 PET/CT for the restaging of patients with biochemically recurrent prostate cancer (BCR)., Methods: This retrospective trial included patients with BCR following radical prostatectomy, who underwent standard whole-body early-phase PET/CT performed 105 ± 45 min and an additional late-phase PET/CT performed 159 ± 13 min after injection of 68  Ga-PSMA-11. Late-phase PET/CT covered a body volume from below the liver to the upper thighs and was conducted after patients had used the bathroom to empty their urinary bladder. Early- and late-phase images were evaluated regarding lesion count, type, localisation, and SUVmax. Reference standard was histopathology and/or follow-up imaging., Results: Whole-body early-phase PET/CT detected 93 prostate cancer lesions in 33 patients. Late-phase PET/CT detected two additional lesions in two patients, both local recurrences. In total, there were 57 nodal, 28 bone, and 3 lung metastases, and 7 local recurrences. Between early- and late-phase PET/CT, lymph node metastases showed a significant increase of SUVmax from 14.5 ± 11.6 to 21.5 ± 17.6 (p = 0.00007), translating to a factor of + 1.6. Benign lymph nodes in the respective regions showed a significantly lower increase of SUVmax of 1.4 ± 0.5 to 1.7 ± 0.5 (p = 0.0014, factor of + 1.2). Local recurrences and bone metastases had a SUVmax on late-phase PET/CT that was + 1.7 and + 1.1 times higher than the SUVmax on early-phase PET/CT, respectively., Conclusion: In patients with BCR following radical prostatectomy, an additional abdomino-pelvic late-phase 68  Ga-PSMA-11 PET/CT scan performed after emptying the urinary bladder may help to detect local recurrences missed on standard whole-body 68  Ga-PSMA-11 PET/CT. Lymph node metastases show a higher SUVmax and a stronger increase of SUVmax than benign lymph nodes on late-phase PET/CT, hence, biphasic 68  Ga-PSMA-11 PET/CT might help to distinguish between malignant and benign nodes. Bone metastases, and especially local recurrences, also demonstrate a metabolic increase over time., (© 2022. The Author(s).)

PURPOSE This study aims to analyze the ability of quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to distinguish between prostate cancer (PCa) and benign lesions in transition zone (TZ) and peripheral zone (PZ) using different methods for arterial input function (AIF) determination. Study endpoints are identification of a standard AIF method and optimal quantitative perfusion parameters for PCa detection. METHODS DCE image data of 50 consecutive patients with PCa who underwent multiparametric MRI were analyzed retrospectively with three different methods of AIF acquisition. First, a region of interest was manually defined in an artery (AIFm); second, an automated algorithm was used (AIFa); and third, a population-based AIF (AIFp) was applied. Values of quantitative parameters after Tofts (Ktrans, ve, and kep) in PCa, PZ, and TZ in the three different AIFs were analyzed. RESULTS Ktrans and kep were significantly higher in PCa than in benign tissue independent from the AIF method. Whereas in PZ, Ktrans and kep could differentiate PCa (P < .001), in TZ only kep using AIFpdemonstrated a significant difference (P = .039). The correlations of the perfusion parameters that resulted from AIFm and AIFa were higher than those that resulted from AIFp, and the absolute values of Ktrans, kep, and ve were significantly lower when using AIFp. The values of quantitative perfusion parameters for PCa were similar regardless of whether PCa was located in PZ or TZ. CONCLUSION Ktrans and kep were able to differentiate PCa from benign PZ independent of the AIF method. AIFaseems to be the most feasible method of AIF determination in clinical routine. For TZ, none of the quantitative perfusion parameters provided satisfying results.

Dynamic contrast enhanced imaging (DCE) as an integral part of multiparametric prostate magnet resonance imaging (mpMRI) can be evaluated using qualitative, semi-quantitative, or quantitative assessment methods. Aim of this study is to analyze the clinical benefits of these evaluations of DCE regarding clinically significant prostate cancer (csPCa) detection and grading. 209 DCE data sets of 103 consecutive patients with mpMRI (T2, DWI, and DCE) and subsequent MRI-(in-bore)-biopsy were retrospectively analyzed. Qualitative DCE evaluation according to PI-RADS v2.1, semi-quantitative (curve type; DCE score according to PI-RADS v1), and quantitative Tofts analyses (Ktrans, kep, and ve) as well as PI-RADS v1 and v2.1 overall classification of 209 lesions (92 PCa, 117 benign lesions) were performed. Of each DCE assessment method, cancer detection, discrimination of csPCa, and localization were assessed and compared to histopathology findings. All DCE analyses (p<0.01-0.05), except ve (p = 0.02), showed significantly different results for PCa and benign lesions in the peripheral zone (PZ) with area under the curve (AUC) values of up to 0.92 for PI-RADS v2.1 overall classification. In the transition zone (TZ) only the qualitative DCE evalulation within PI-RADS (v1 and v2.1) could distinguish between PCa and benign lesions (p<0.01; AUC = 0.95). None of the DCE parameters could differentiate csPCa from non-significant (ns) PCa (p ≥ 0.1). Qualitative analysis of DCE within mpMRI according to PI-RADS version 2.1 showed excellent results regarding (cs)PCa detection. Semi-quantitative and quantitative parameters provided no additional improvements. DCE alone wasn't able to discriminate csPCa from nsPCa., Competing Interests: The authors have declared that no competing interests exist.

We aimed to investigate the relation between largest lesion diameter, prostate-specific antigen density (PSA-D), age, and the detection of clinically significant prostate cancer (csPCa) using first-time targeted biopsy (TBx) in men with Prostate Imaging-Reporting and Data System (PI-RADS) 3 index lesions. A total of 292 men (2013-2019) from two referral centers were included. A multivariable logistic regression analysis was performed. The discrimination and clinical utility of the built model was assessed by the area under the receiver operation curve (AUC) and decision curve analysis, respectively. A higher PSA-D and higher age were significantly related to a higher risk of detecting csPCa, while the largest index lesion diameter was not. The discrimination of the model was 0.80 (95% CI 0.73-0.87). When compared to a biopsy-all strategy, decision curve analysis showed a higher net benefit at threshold probabilities of ≥2%. Accepting a missing ≤5% of csPCa diagnoses, a risk-based approach would result in 34% of TBx sessions and 23% of low-risk PCa diagnoses being avoided. In men with PI-RADS 3 index lesions scheduled for first-time TBx, the balance between the number of TBx sessions, the detection of low-risk PCa, and the detection of csPCa does not warrant a biopsy-all strategy. To minimize the risk of missing the diagnosis of csPCa but acknowledging the need of avoiding unnecessary TBx sessions and overdiagnosis, a risk-based approach is advisable.

Background: Erectile dysfunction (ED) is a common public health issue with a significant impact on quality of life. The associations between ED and several risk factors have been reported previously. The continuously increasing incidence of these factors is contributing to the increasing prevalence of ED., Aim: To assess ED prevalence and severity in a representative sample of 45-year-old German men and to analyze the association with risk factors (lifestyle risk factors/comorbidities)., Methods: Data were collected within the German Male Sex-Study. Randomly selected 45-year-old men were invited. A total of 10,135 Caucasian, heterosexual, sexually active men were included in this analysis. The self-reported prevalence of ED was assessed using the Erectile Function domain of the International Index of Erectile Function. Risk factors for ED were ascertained using self-report questionnaires. An anamnesis interview and a short physical examination were performed., Main Outcome Measure: ED prevalence and severity were evaluated in a cross-sectional design. The associations of ED with comorbidities (eg, depression, diabetes, hypertension, lower urinary tract symptoms) and lifestyle factors (ie, smoking, obesity, central obesity, physical inactivity, and poor self-perceived health-status) were analyzed by logistic regression., Results: The overall prevalence of ED was 25.2% (severe, 3.1%; moderate, 9.2%; mild to moderate, 4.2%; mild, 8.7%). Among the men with ED, 48.8% had moderate or severe symptoms. ED prevalence increased with the number of risk factors, to as high as 68.7% in men with 5-8 risk factors. In multiple logistic regression with backward elimination, the strongest associations with ED were found for depression (odds ratio [OR] = 1.87), poor self-perceived health status (OR = 1.72), lower urinary tract symptoms (OR = 1.68), and diabetes (OR = 1.38)., Conclusion: One out of 4 men already had symptoms of ED at age 45. Almost one-half of the men with ED had moderate to severe symptoms. ED was strongly associated with each analyzed risk factor, and the prevalence and severity of ED increased with an increasing number of risk factors. Hallanzy J, Kron M, Goethe VE, et al. Erectile Dysfunction in 45-Year-Old Heterosexual German Men and Associated Lifestyle Risk Factors and Comorbidities: Results From the German Male Sex Study. Sex Med 2019;7:26-34., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Discordance of various aspects of sexual orientation has been mostly studied in young adults or in small samples of heterosexual men. Studies focusing on concordance and discordance of aspects of sexual orientation in representative samples of middle-aged men including homosexual men are scarce., Aim: To investigate concordant and discordant sexual behavior in 45-year-old German men with a special focus on homosexual identified men., Methods: Data for this cross-sectional study were collected within the German Male Sex-Study. Participants were 45-year-old Caucasian males from the general population. Men self-reported on sexual identity, sexual experience, and current sexual behavior. Associations between sexual identity, experience, and behavior were analyzed using the chi-square test., Main Outcome Measure: Associations of sexual identity with sexual experience and behavior in a community-based sample of men, and discordance of sexual identity and behavior especially in the subgroup of homosexual men., Results: 12,354 men were included in the study. 95.1% (n = 11.749) self-identified as heterosexual, 3.8% (n = 471) as homosexual, and 1.1% (n = 134) as bisexual. Sexual identity was significantly associated with sexual experience and behavior. 85.5% of all men had recently been sexually active, but prevalence of sexual practices varied. In hetero- and bisexuals, vaginal intercourse was the most common sexual practice, whereas oral sex was the most common in homosexuals. A discordance of sexual identity was especially found in homosexual men: 5.5% of homosexuals only had sexual experiences with women, and 10.3% of homosexuals recently had vaginal intercourse. In this latter subgroup, only one-quarter ever had sexual experience with a man, and three-quarters had only engaged in sexual activity with a woman., Conclusion: Sexual identity is associated with differences in sexual experience and behavior in German middle-aged men. A considerable proportion of homosexual identified men live a heterosexual life. Goethe VE, Angerer H, Dinkel A, et al. Concordance and Discordance of Sexual Identity, Sexual Experience, and Current Sexual Behavior in 45-Year-Old-Men: Results From the German Male Sex-Study. Sex Med 201;6:282-290., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Limitations of current diagnostic and prognostic tools for prostate cancer (PC) have led to over-diagnosis and over-treatment. Here, we investigate the biomarker potential of the SLC18A2 (VMAT2) gene for PC at three molecular levels. Thus, SLC18A2 promoter methylation was analyzed in 767 malignant and 78 benign radical prostatectomy (RP) samples using methylation-specific qPCR and Illumina 450K methylation microarray data. SLC18A2 transcript levels were assessed in 412 malignant and 45 benign RP samples using RNAseq data. SLC18A2 protein was evaluated by immunohistochemistry in 502 malignant and 305 benign RP samples. Cancer-specificity of molecular changes was tested using Mann-Whitney U tests and/or receiver operating characteristic (ROC) analyses. Log rank, uni- and multivariate Cox regression tests were used for survival analyses. We found that SLC18A2 promoter hypermethylation was highly cancer-specific (area under the curve (AUC): 0.923-0.976) and associated with biochemical recurrence (BCR) after RP in univariate analyses. SLC18A2 transcript levels were reduced in PC and had independent prognostic value for BCR after RP (multivariate HR 0.13, P < 0.05). Likewise, SLC18A2 protein was down-regulated in PC (AUC 0.898) and had independent prognostic value for BCR (multivariate HR 0.51, P < 0.05). Reduced SLC18A2 protein expression was also associated with poor overall survival in univariate analysis (HR 0.29, P < 0.05). Our results highlight SLC18A2 as a new promising methylation marker candidate for PC diagnosis. Furthermore, SLC18A2 expression (RNA and protein) showed promising prognostic potential beyond routine clinicopathological variables. Thus, novel SLC18A2-based molecular tests could have useful future applications for PC detection and identification of high-risk patients., (Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.)

Background/aim: Initial inaccurate staging is a common problem associated with active surveillance (AS) for patients detected by transrectal ultrasound-guided prostate biopsy (TRUS-GB). Subsequently, repeated biopsies are necessary to monitor such patients. Thus, in addition to the already established clinicopathological criteria, there is a considerable demand for new, objective decision criteria to more accurately select AS candidates. Recently, a novel RNA expression signature derived from 31 cell-cycle progression (CCP) genes has been shown to be a strong predictor of outcome in patients after radical prostatectomy or radiotherapy. This is a qualitative pilot study to evaluate the prognostic value of the CCP-score (CCP-S) for the first time in men managed with AS after MRI-guided prostate biopsy (MRI-GB)., Patients and Methods: Nine patients previously diagnosed with prostate cancer during an ongoing, prospective trial assessing MRI-GB with additional TRUS-GB and were subsequently managed with AS. CCP-S were retrospectively derived from biopsy specimens. The CCP-S is defined as the expression level of 31 CCP genes, normalized to 15 housekeeping genes, and is clinically validated in a range between -1.3 and 4.7. To assess the estimated 10-year mortality risk (without curative treatment), the CCP-S from each patient was combined with the individual CAPRA (Cancer of the Prostate Risk Assessment) score (CAPRA-S)., Results: Median patient age was 72 (range=58-77) years. Mean pre-biopsy PSA level was 6.33±1.94 (range 4.23-9.97) ng/ml. Eight cases had Gleason score 6 (3+3) and one cancer had Gleason score 7 (3+4). Median CCP-S was -0.9 (range=-1.5 to 0.0). Combining CCP-S with CAPRA-S [CAPRA-S: 1 (n=4), 2 (n=4), 3 (n=1)] the estimated 10-year mortality risk was not calculable for three patients because their CCP-S [CCP-S -1.4 (n=2) and -1.5 (n=1)] was outside the validated range. For the other 6 patients the estimated 10-year mortality ranged from 1.0-3.0%., Conclusion: The CCP-S confirms accurate staging of AS patients detected by MRI-based biopsy strategies and may significantly reduce inaccurate staging of AS patients and subsequent unnecessary re-biopsies. The CCP score may help to more accurately select for active surveillance candidates.

Purpose: Available tools for prostate cancer diagnosis and prognosis are suboptimal and novel biomarkers are urgently needed. Here, we investigated the regulation and biomarker potential of the GABRE∼miR-452∼miR-224 genomic locus., Experimental Design: GABRE/miR-452/miR-224 transcriptional expression was quantified in 80 nonmalignant and 281 prostate cancer tissue samples. GABRE∼miR-452∼miR-224 promoter methylation was determined by methylation-specific qPCR (MethyLight) in 35 nonmalignant, 293 prostate cancer [radical prostatectomy (RP) cohort 1] and 198 prostate cancer tissue samples (RP cohort 2). Diagnostic/prognostic biomarker potential of GABRE∼miR-452∼miR-224 methylation was evaluated by ROC, Kaplan-Meier, uni- and multivariate Cox regression analyses. Functional roles of miR-224 and miR-452 were investigated in PC3 and DU145 cells by viability, migration, and invasion assays and gene-set enrichment analysis (GSEA) of posttransfection transcriptional profiling data., Results: GABRE∼miR-452∼miR-224 was significantly downregulated in prostate cancer compared with nonmalignant prostate tissue and had highly cancer-specific aberrant promoter hypermethylation (AUC = 0.98). Functional studies and GSEA suggested that miR-224 and miR-452 inhibit proliferation, migration, and invasion of PC3 and DU145 cells by direct/indirect regulation of pathways related to the cell cycle and cellular adhesion and motility. Finally, in uni- and multivariate analyses, high GABRE∼miR-452∼miR-224 promoter methylation was significantly associated with biochemical recurrence in RP cohort 1, which was successfully validated in RP cohort 2., Conclusion: The GABRE∼miR-452∼miR-224 locus is downregulated and hypermethylated in prostate cancer and is a new promising epigenetic candidate biomarker for prostate cancer diagnosis and prognosis. Tumor-suppressive functions of the intronic miR-224 and miR-452 were demonstrated in two prostate cancer cell lines, suggesting that epigenetic silencing of GABRE∼miR-452∼miR-224 may be selected for in prostate cancer., (©2014 AACR.)

Background/aim: Patients with previous negative transrectal ultrasound-guided biopsy (TRUS-GB) and persistently increased prostate-specific antigen (PSA) value represent a great diagnostic problem. Magnetic resonance imaging (MRI)-guided biopsy demonstrates high prostate cancer detection rates in these patients if functional MRI is suspicious for prostate cancer. However, MRI-guided biopsy is not commonly available and features considerable technical requirements. This was a pilot study to investigate if a standard repeat TRUS-GB, with additional targeted cores to suspicious lesions on functional MRI, can achieve similar detection rates as compared to MRI-guided biopsy., Patients and Methods: 3 Tesla functional MRI was performed in 58 patients with ≥1 previous negative biopsy, persistently increased PSA ≥4 ng/ml and unsuspicious digital rectal examination. Suspicious lesions were marked on a localization map to enable their finding on TRUS. Random TRUS-GB with additional targeted cores according to the functional MRI findings were performed in patients with ≥1 suspicious lesion., Results: In 37.9% (22/58), functional MRI demonstrated suspicious findings. Out of these 22 patients, 16 underwent TRUS-GB with additional targeted cores. Prostate cancer was diagnosed in 68.8% (11/16). Eight out of these 11 patients subsequently underwent radical prostatectomy and all tumors fulfilled criteria for high-risk prostate cancer. With a median follow-up of 49.1 weeks neither significant PSA increase nor prostate cancer was detected in patients with normal functional MRI findings., Conclusion: Our approach enables excellent detection rates of clinically significant prostate cancer in patients with ≥1 previous negative biopsy and persistently increased PSA levels. Due to the current disadvantages of MRI-guided biopsy, our approach therefore represents an excellent alternative to MRI-guided biopsy.