Effect of 5-Alpha Reductase Inhibitors on Magnetic Resonance Imaging and Prostate Cancer Detection.

Concerns exist regarding the effects of 5-alpha reductase inhibitors (5-ARIs) on multipa-rametric magnetic resonance imaging (mpMRI) and clinically significant prostate cancer (csPCa) detection. Our objective is to analyze the effect of 5-ARI on the prostate imaging-reporting and data system (PI-RADS) distribution and csPCa and insignificant PCa (iPCa) detection. Among 2212 men with serum prostate-specific antigen levels of >3.0 ng/mL and/or suspicious digital rectal examinations who underwent mpMRI and targeted and/or systematic biopsies, 120 individuals exposed to 5-ARI treatment for over a year were identified. CsPCa was defined when the grade group (GG) was >2. The overall csPCa and iPCa detection rates were 44.6% and 18.8%, respectively. Since logistic regression revealed independent predictors of PCa, a randomized matched group of 236 individuals was selected for analysis. The PI-RADS distribution was comparable with 5-ARI exposure (p 0.685). The CsPCa detection rates in 5-ARI-naïve men and 5-ARI-exposed men were 52.6% and 47.4%, respectively (p 0.596). IPCa was detected in 37.6 and 62.5%, respectively (p 0.089). The tumor GG distribution based on 5-ARI exposure was similar (p 0.149) to the rates of csPCa and iPCa across the PI-RADS categories. We conclude that exposure to 5-ARI in suspected PCa men did not change the PI-RADS distribution and the csPCa and iPCa detection rates.

Reducing the demand for magnetic resonance imaging scans and prostate biopsies during the early detection of clinically significant prostate cancer: Applying the Barcelona risk-stratified pathway in Catalonia.

PURPOSE: To analyze the reduction in multiparametric magnetic resonance imaging (mpMRI) demand and prostate biopsies after the hypothetical implementation of the Barcelona risk-stratified pathway (BCN-RSP) in a population of the clinically significant prostate cancer (csCaP) early detection program in Catalonia. MATERIALS AND METHODS: A retrospective comparation between the hypothetical application of the BCN-RSP and the current pathway, which relied on pre-biopsy mpMRI and targeted and/or systematic biopsies, was conducted. The BCN-RSP stratify men with suspected CaP based on a prostate specific antigen (PSA) level >10 ng/ml and a suspicious rectal examination (DRE), and the Barcelona-risk calculator 1 (BCN-RC1) to avoid mpMRI scans. Subsequently, candidates for prostate biopsy following mpMRI are selected based on the BCN-RC2. This comparison involved 3,557 men with serum PSA levels > 3.0 ng/ml and/or suspicious DRE. The population was recruited prospectively in 10 centers from January 2021 and December 2022. CsCaP was defined when grade group ≥ 2. RESULTS: CsCaP was detected in 1,249 men (35.1%) and insignificant CaP was overdeteced in 498 (14%). The BCN-RSP would have avoid 705 mpMRI scans (19.8%), and 697 prostate biopsies (19.6%), while 61 csCaP (4.9%) would have been undetected. The overdetection of insignificant CaP would have decrease in 130 cases (26.1%), and the performance of prostate biopsy for csCaP detection would have increase to 41.5%. CONCLUSION: The application of the BCN-RSP would reduce the demand for mpMRI scans and prostate biopsies by one fifth while less than 5% of csCaP would remain undetected. The overdetection of insignificant CaP would decrease by more than one quarter and the performance of prostate biopsy for csCaP detection would increase to higher than 40%.

The Role of Digital Rectal Examination Prostate Volume Category in the Early Detection of Prostate Cancer: Its Correlation with the Magnetic Resonance Imaging Prostate Volume.

PURPOSE: To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)-small, median, and large-and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DRE-PVC and MRI-PV. MATERIALS AND METHODS: A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%. RESULTS: The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19-37 mL) and 35 mL (23-30 mL), p=0.410; in median prostates they were 51 mL (38-58 mL) and 55 mL (48-63 mL) respectively, p<0.001; in large prostates 80 mL (60-100 mL) and 95 mL (75-118 mL) respectively, p<0.001. The predictive models sharing the MRI-PV and DRE-PVC showed areas under the curves of 0.832 (95% confidence interval [CI], 0.813-0.851) and 0.828 (95% CI, 0.809-0.848) respectively, p=0.632, as well as similar net benefit and clinical utility. CONCLUSIONS: PVC was unconclusive in 17% of DREs. MRI-PV overestimated the TRUS-PV in median and large prostates. The predictive models based on MRI-PV and DRE-PVC showed similar efficacy to predict csPCa. PVC assessed with DRE is helpful to predict the csPCa risk before MRI.

In silico analysis of prognostic and diagnostic significance of target genes from prostate cancer cell lines derived exomicroRNAs.

BACKGROUND: Cancer-secreted exovesicles are important for cell-to-cell communication by altering cancer-related signalling pathways. Exovesicles-derived miRNAs (exomiRNAs)-target genes can be useful for diagnostic and prognostic purposes. METHODS: ExomiRNA from prostate cancer (PCa) cells (PC-3 and LNCaP) were quantified by qRT-PCR and compared to the healthy cell line RWPE-1 by using miRNome PCR 752 miRNAs Panel. MiRNet database was used to predict exomiRNA-target genes. ExomiRNA-target genes pathway functional enrichment was performed by using Reactome database and Enrichr platform. Protein-protein interaction analysis was carried out by using the STRING database. RNA target-gene sequencing data from The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) database was screened out in 465 PCa patients for candidate gene expression in prostate tumour (PT) tissue and non-pathologic prostate (N-PP) tissue. Signature gene candidates were statistically analysed for diagnosis and prognosis usefulness. RESULTS: A total of 36 exomiRNAs were found downregulated when comparing PCa cells vs a healthy cell line; and when comparing PC-3 vs LNCaP, 14 miRNAs were found downregulated and 52 upregulated. Reactome pathway database revealed altered pathways and genes related to miRNA biosynthesis, miRNA-mediated gene silencing (TNRC6B and AGO1), and cell proliferation (CDK6), among others. Results showed that TNRC6B gene expression was up-regulated in PT tissue compared to N-PP (n = 52 paired samples) and could be useful for diagnostic purposes. Likewise, gene expression levels of CDK6, TNRC6B, and AGO1 were down-regulated in high-risk PT (n = 293) compared to low-risk PCa tissue counterparts (n = 172). When gene expression levels of CDK6, TNRC6B, and AGO1 were tested as a prognostic panel, the results showed that these improve the prognostic power of classical biomarkers. CONCLUSION: ExomiRNAs-targets genes, TNRC6B, CDK6, and AGO1, showed a deregulated expression profile in PCa tissue and could be useful for PCa diagnosis and prognosis.

A Diagnostic Accuracy Study of Targeted and Systematic Biopsies to Detect Clinically Significant Prostate Cancer, including a Model for the Partial Omission of Systematic Biopsies.

The primary objective of this study was to analyse the current accuracy of targeted and systematic prostate biopsies in detecting csPCa. A secondary objective was to determine whether there are factors predicting the finding of csPCa in targeted biopsies and, if so, to explore the utility of a predictive model for csPCa detection only in targeted biopsies. We analysed 2122 men with suspected PCa, serum PSA > 3 ng/mL, and/or a suspicious digital rectal examination (DRE), who underwent targeted and systematic biopsies between 2021 and 2022. CsPCa (grade group 2 or higher) was detected in 1026 men (48.4%). Discrepancies in csPCa detection in targeted and systematic biopsies were observed in 49.6%, with 13.9% of csPCa cases being detected only in systematic biopsies and 35.7% only in targeted biopsies. A predictive model for csPCa detection only in targeted biopsies was developed from the independent predictors age (years), prostate volume (mL), PI-RADS score (3 to 5), mpMRI Tesla (1.5 vs. 3.0), TRUS-MRI fusion image technique (cognitive vs. software), and prostate biopsy route (transrectal vs. transperineal). The csPCa discrimination ability of targeted biopsies showed an AUC of 0.741 (95% CI 0.721-0.762). The avoidance rate of systematic prostate biopsies went from 0.5% without missing csPCa to 18.3% missing 4.6% of csPCa cases. We conclude that the csPCa diagnostic accuracy of targeted biopsies is higher than that of systematic biopsies. However, a significant rate of csPCa remains detected only in systematic biopsies. A predictive model for the partial omission of systematic biopsies was developed.

Are magnetic resonance imaging and targeted biopsies needed in men with serum prostate-specific antigen over 10 ng/ml and an abnormal digital rectal examination?

The European Association of Urology currently recommends the use of risk-organized models to decrease the demand of prebiopsy magnetic resonance imaging (MRI) and unnecessary prostate biopsies in men with suspected prostate cancer (CaP). Low evidence suggests that men with prostate-specific antigen >10 ng/ml and an abnormal digital rectal examination (DRE) do not benefit from prebiopsy MRI and targeted biopsies. We aim to validate this low evidence in a sizable cohort and knowing how many clinically significant CaP (csCaP) would go undetected if only random biopsies were performed in these cases. We analyze a subset of 545 men with PSA >10 ng/ml and an abnormal DRE who met the previous criteria among 5,329 participants in a prospective trial in whom random biopsy was always performed and targeted biopsies of PI-RADS ≥3 lesions (10.2%). CsCaP (grade group ≥2) was detected in 370 men (67.9%), with 11 of 49 with negative MRI (22.5%) and 359 of 496 (72.4%) having PI-RADS ≥3. CsCaP was identified in random and targeted biopsies in 317 (88.7%) men, in targeted biopsies only in 23 (6.4%), and in random biopsies only in 19 (5.3%). If only random biopsies were performed in these men, 23 of overall 1,914 csCaP (1.2%) would go undetected in this population. Prebiopsy MRI can be saved in men with serum PSA >10 ng/ml and an abnormal DRE and only random biopsy performed. However, a close follow-up of men with negative random biopsy seems appropriate due to the high-risk of csCaP in these men.

The lipidomic profile of the tumoral periprostatic adipose tissue reveals alterations in tumor cell's metabolic crosstalk.

BACKGROUND: Periprostatic adipose tissue (PPAT) plays a role in prostate cancer (PCa) progression. PPAT lipidomic composition study may allow us to understand the tumor metabolic microenvironment and provide new stratification factors. METHODS: We used ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics to profile lipids in the PPAT of 40 patients with PCa (n = 20 with low-risk and n = 20 high-risk). Partial least squares-discriminant analysis (PLS-DA) and variable importance in projection (VIP) analysis were used to identify the most relevant features of PPAT between low- and high-risk PCa, and metabolite set enrichment analysis was used to detect disrupted metabolic pathways. Metabolic crosstalk between PPAT and PCa cell lines (PC-3 and LNCaP) was studied using ex vivo experiments. Lipid uptake and lipid accumulation were measured. Lipid metabolic-related genes (SREBP1, FASN, ACACA, LIPE, PPARG, CD36, PNPLA2, FABP4, CPT1A, FATP5, ADIPOQ), inflammatory markers (IL-6, IL-1B, TNFα), and tumor-related markers (ESRRA, MMP-9, TWIST1) were measured by RT-qPCR. RESULTS: Significant differences in the content of 67 lipid species were identified in PPAT samples between high- and low-risk PCa. PLS-DA and VIP analyses revealed a discriminating lipidomic panel between low- and high-risk PCa, suggesting the occurrence of disordered lipid metabolism in patients related to PCa aggressiveness. Functional analysis revealed that alterations in fatty acid biosynthesis, linoleic acid metabolism, and ß-oxidation of very long-chain fatty acids had the greatest impact in the PPAT lipidome. Gene analyses of PPAT samples demonstrated that the expression of genes associated with de novo fatty acid synthesis such as FASN and ACACA were significantly lower in PPAT from high-risk PCa than in low-risk counterparts. This was accompanied by the overexpression of inflammatory markers (IL-6, IL-1B, and TNFα). Co-culture of PPAT explants with PCa cell lines revealed a reduced gene expression of lipid metabolic-related genes (CD36, FASN, PPARG, and CPT1A), contrary to that observed in co-cultured PCa cell lines. This was followed by an increase in lipid uptake and lipid accumulation in PCa cells. Tumor-related genes were increased in co-cultured PCa cell lines. CONCLUSIONS: Disturbances in PPAT lipid metabolism of patients with high-risk PCa are associated with tumor cell metabolic changes.

Serum Levels of the Cytokine TWEAK Are Associated with Metabolic Status in Patients with Prostate Cancer and Modulate Cancer Cell Lipid Metabolism In Vitro.

Soluble TWEAK (sTWEAK) has been proposed as a prognostic biomarker of prostate cancer (PCa). We found that reduced serum levels of sTWEAK, together with higher levels of prostate-specific antigen and a higher HOMA-IR index, are independent predictors of PCa. We also showed that sTWEAK stimulus failed to alter the expression of glucose transporter genes (SLC2A4 and SLC2A1), but significantly reduced the expression of glucose metabolism-related genes (PFK, HK1 and PDK4) in PCa cells. The sTWEAK stimulation of PC-3 cells significantly increased the expression of the genes related to lipogenesis (ACACA and FASN), lipolysis (CPT1A and PNPLA2), lipid transport (FABP4 and CD36) and lipid regulation (SREBP-1 and PPARG) and increased the lipid uptake. Silencing the TWEAK receptor (Fn14) in PC-3 cells confirmed the observed lipid metabolic effects, as shown by the downregulation of ACACA, FASN, CPT1A, PNPLA2, FABP4, CD36, SREBP-1 and PPARG expression, which was paralleled by a reduction of FASN, CPT1A and FABP4 protein expression. Specific-signaling inhibitor assays show that ERK1/2 and AKT (ser473) phosphorylation can regulate lipid metabolism-related genes in PCa cells, pointing to the AKT locus as a possible target for PCa. Overall, our data support sTWEAK/Fn14 axis as a potential therapeutic target for PCa.

Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness.

Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in post-digital rectal examination urine from patients with different degrees of PCa aggressiveness. We first identified 14 exo-oncomiRNAs regulated by TWEAK in PCa cells in vitro, and subsequently validated those using liquid biopsies from 97 patients with PCa. Exo-oncomiR-221-3p, -222-3p and -31-5p were significantly higher in the semen of high-risk patients than in low-risk peers, whereas exo-oncomiR-193-3p and -423-5p were significantly lower in paired samples of post-digital rectal examination urine. A panel of semen biomarkers comprising exo-oncomiR-221-3p, -222-3p and TWEAK was designed that could correctly classify 87.5% of patients with aggressive PCa, with 85.7% specificity and 76.9% sensitivity with an area under the curve of 0.857. We additionally found that TWEAK modulated two exo-oncomiR-221-3p targets, TCF12 and NLK. Overall, we show that liquid biopsy detection of TWEAK-regulated exo-oncomiRNAs can improve PCa prognosis prediction.

Biofluid quantification of TWEAK/Fn14 axis in combination with a selected biomarker panel improves assessment of prostate cancer aggressiveness.

BACKGROUND: Conventional clinical biomarkers cannot accurately differentiate indolent from aggressive prostate cancer (PCa). We investigated the usefulness of a biomarker panel measured exclusively in biofluids for assessment of PCa aggressiveness. METHODS: We collected biofluid samples (plasma/serum/semen/post-prostatic massage urine) from 98 patients that had undergone radical prostatectomy. Clinical biochemistry was performed and several cytokines/chemokines including soluble(s) TWEAK, sFn14, sCD163, sCXCL5 and sCCL7 were quantified by ELISA in selected biofluids. Also, the expression of KLK2, KLK3, Fn14, CD163, CXCR2 and CCR3 was quantified by real-time PCR in semen cell sediment. Univariate, logistic regression, and receiver operating characteristic (ROC) analyses were used to assess the predictive ability of the selected biomarker panel in conjunction with clinical and metabolic variables for the evaluation of PCa aggressiveness. RESULTS: Total serum levels of prostate-specific antigen (PSA), semen levels of sTWEAK, fasting glycemia and mRNA levels of Fn14, KLK2, CXCR2 and CCR3 in semen cell sediment constituted a panel of markers that was significantly different between patients with less aggressive tumors [International Society of Urological Pathology (ISUP) grade I and II] and those with more aggressive tumors (ISUP grade III, IV and V). ROC curve analysis showed that this panel could be used to correctly classify tumor aggressiveness in 90.9% of patients. Area under the curve (AUC) analysis revealed that this combination was more accurate [AUC = 0.913 95% confidence interval (CI) 0.782-1] than a classical non-invasive selected clinical panel comprising age, tumor clinical stage (T-classification) and total serum PSA (AUC = 0.721 95% CI 0.613-0.830). CONCLUSIONS: TWEAK/Fn14 axis in combination with a selected non-invasive biomarker panel, including conventional clinical biochemistry, can improve the predictive power of serum PSA levels and could be used to classify PCa aggressiveness.

Cuerpo extraño intravesical / Bladder foreign body

No disponible

Quiste hidatídico retroperitoneal / Retroperitoneal hydatid cyst

No disponible

Estallido testicular tras lesión por arma de fuego / Testicular rupture after gun shot injury

No disponible

Rectoprostatic fistula: unusual presentation of a prostatic abscess.

OBJECTIVE: To present the case and iconography of a rectoprostatic fistula as a form of presentation of a prostatic abscess and to review the literature on the diagnosis and treatment of this pathology. METHODS: 69-year-old male with multiple pathologic conditions who presents an orifice in the prostatic fossa on digital rectal examination in the scenario of a urinary tract infection with fever. CT scan and colonoscopy showed a prostatic abscess fistulizing to rectum. RESULTS: Due to spontaneous drainage of the abscess, conservative treatment with intravenous fluid therapy and antibiotics was chosen. CONCLUSIONS: Prostatic abscess is often difficult to diagnose because of its low prevalence and unspecific symptomatology. Since the introduction of antibiotics, cases in which abscess fistulas or opens spontaneously to neighboring structures like urethra or rectum have decreased.

Fístula recto-prostática. Una presentación inusual de un absceso prostático / Rectoprostatic fistula: Unusual presentation of a prostatic abscess

OBJETIVO: Comunicar el caso y la iconografía de una fístula recto-prostática como forma de presentación de un absceso prostático y revisar brevemente la literatura sobre el diagnóstico y tratamiento de esta patología.MÉTODOS: Varón de 69 años con pluripatología de base que en el contexto de una infección urinaria febril presenta al tacto rectal un orificio en celda prostática apreciándose en TAC y colonoscopia, un absceso prostático fistulizado a recto.RESULTADOS: Ante el drenaje espontáneo del absceso se optó por el tratamiento conservador con sueroterapia y antibioterapia.CONSCLUSIONES: El absceso prostático es una entidad de difícil diagnóstico por su baja prevalencia y su sintomatología inespecífica. Desde la aparición de los antibióticos son cada vez menos los casos que fistulizan o abren espontáneamente a estructuras vecinas como uretra o recto(AU)

OBJECTIVE: To present the case and iconography of a rectoprostatic fistula as a form of presentation of a prostatic abscess and to review the literature on the diagnosis and treatment of this pathology.METHODS: 69-year-old male with multiple pathologic conditions who presents an orifice in the prostatic fossa on digital rectal examination in the scenario of a urinary tract infection with fever. CT scan and colonoscopy showed a prostatic abscess fistulizing to rectum.RESULTS: Due to spontaneous drainage of the abscess, conservative treatment with intravenous fluid therapy and antibiotics was chosen.CONSCLUSIONS: Prostatic abscess is often difficult to diagnose because of its low prevalence and unspecific symptomatology. Since the introduction of antibiotics, cases in which abscess fistulises or opens spontaneously to neighboring structures like urethra or rectum have decreased(AU)