Prospective study of diagnostic accuracy in the detection of high-grade prostate cancer in biopsy-naïve patients with clinical suspicion of prostate cancer who underwent the Select MDx test

[Objectives] This study aimed to externally validate the diagnostic accuracy of the Select MDx test for Significant prostate cancer (Sig PCa) (ISUP > 1), in a contemporaneous, prospective, multicenter cohort with a prostate-specific antigen (PSA) between 3 and 10 ng/ml and a non-suspicious digital rectal examination.[Methods and Participants] For all enrolled patients, the Select Mdx test, the risk calculator ERSPC3 + DRE, and a prostatic magnetic resonance imaging (MRI) were carried out. Subsequently, a systematic 12-core trans-rectal biopsy and a targeted biopsy, in the case of a prostate imaging–reporting and data system (PIRADS) > 2 lesion (max three lesions), were performed. To assess the accuracy of the Select MDx test in the detection of clinically Sig PCa, the test sensitivity was evaluated. Secondary objectives were specificity, negative predictive value (NPV), positive predictive value (PPV), and area under the curve (AUC). A direct comparison with the ERSPC + DRE risk calculator and MRI were also performed. We also studied the predictive ability to diagnose Sig PCa from the combination of the Select MDx test with MRI using clinical decision-curve analysis.[Results] There were 163 patients enrolled after meeting the inclusion criteria and study protocol. The Select MDx test showed a sensitivity of 76.9% (95% CI, 63.2–87.5), 49.6% specificity (95% CI, 39.9–59.2), 82.09% (95% CI, 70.8–90.4) NPV, and 41.67% (95% CI, 31.7–52.2) PPV for the diagnosis of Sig PCa. COR analysis was also performed, which showed an AUC of 0.63 (95% CI, 0.56–0.71). There were no differences in the accuracy of Select MDx, ERSPC + DRE, or MRI. The combination of Select MDX + MRI showed the highest impact in the decision-curve analysis, with an NPV of 93%.[Conclusion] Our study showed a worse performance for the SelectMdx test than previously reported, within a cohort of patients with a PSA 3–10 ng/ml and a normal DRE, with results similar to those from ERSPC + DRE RC and MRI, but with an improvement in the usual PSA pathway. A combination of the Select Mdx test and MRI could improve accuracy, but studies specifically evaluating this scenario with a cost-effective analysis are needed.This study received grant support from Ferrer to support the test performance, research meetings, and Central Registration Depository and CRO monitoring of the information platform for multicenter studies (AEU-PIEM/2018/0004).Peer reviewe

Clinical Utility of Ghrelin-O-Acyltransferase (GOAT) Enzyme as a Diagnostic Tool and Potential Therapeutic Target in Prostate Cancer

Recent data suggested that plasma Ghrelin O-Acyl Transferase enzyme (GOAT) levels could represent a new diagnostic biomarker for prostate cancer (PCa). In this study, we aimed to explore the diagnostic and prognostic/aggressiveness capacity of GOAT in urine, as well as to interrogate its putative pathophysiological role in PCa. We analysed urine/plasma levels of GOAT in a cohort of 993 patients. In vitro (i.e., cell-proliferation) and in vivo (tumor-growth in a xenograft-model) approaches were performed in response to the modulation of GOAT expression/activity in PCa cells. Our results demonstrate that plasma and urine GOAT levels were significantly elevated in PCa patients compared to controls. Remarkably, GOAT significantly outperformed PSA in the diagnosis of PCa and significant PCa in patients with PSA levels ranging from 3 to 10 ng/mL (the so-called PSA grey-zone). Additionally, urine GOAT levels were associated to clinical (e.g., Gleason-score, PSA levels) and molecular (e.g., CDK2/CDK6/CDKN2A expression) aggressiveness parameters. Indeed, GOAT overexpression increased, while its silencing/blockade decreased cell-proliferation in PCa cells. Moreover, xenograft tumors derived from GOAT-overexpressing PCa (DU145) cells were significantly higher than those derived from the mock-overexpressing cells. Altogether, our results demonstrate that GOAT could be used as a diagnostic and aggressiveness marker in urine and a therapeutic target in PCa

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere’s Disease

Meniere’s disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627); p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD

CE-MS-based urinary biomarkers to distinguish non-significant from significant prostate cancer.

Prostate cancer progresses slowly when present in low risk forms but can be lethal when it progresses to metastatic disease. A non-invasive test that can detect significant prostate cancer is needed to guide patient management. Capillary electrophoresis/mass spectrometry has been employed to identify urinary peptides that may accurately detect significant prostate cancer. Urine samples from 823 patients with PSA ( Independent validation of the 19-biomarker model in 280 patients resulted in a 90% sensitivity and 59% specificity, with an AUC of 0.81, outperforming PSA (AUC = 0.58) and the ERSPC-3/4 risk calculator (AUC = 0.69) in the validation set. This multi-parametric model holds promise to improve the current diagnosis of significant prostate cancer. This test as a guide to biopsy could help to decrease the number of biopsies and guide intervention. Nevertheless, further prospective validation in an external clinical cohort is required to assess the exact performance characteristics

Clinical association of metabolic syndrome, C-reactive protein and testosterone levels with clinically significant prostate cancer.

Recently, the influence that metabolic syndrome (MetS), hormonal alterations and inflammation might have on prostate cancer (PCa) risk has been a subject of controversial debate. Herein, we aimed to investigate the association between MetS-components, C-reactive protein (CRP) and testosterone levels, and the risk of clinically significant PCa (Sig-PCa) at the time of prostate biopsy. For that, men scheduled for transrectal ultrasound guided biopsy of the prostate were studied. Clinical, laboratory parameters and criteria for MetS characterization just before the biopsy were collected. A total of 524 patients were analysed, being 195 (37.2%) subsequently diagnosed with PCa and 240 (45.8%) meet the diagnostic criteria for MetS. Among patients with PCa, MetS-diagnosis was present in 94 (48.2%). Remarkably, a higher risk of Sig-PCa was associated to MetS, greater number of MetS-components and higher CRP levels (odds-ratio: 1.83, 1.30 and 2.00, respectively; P 2.5 mg/L with an increased Sig-PCa diagnosis and/or with aggressive features, suggesting that MetS and/or CRP levels might influence PCa pathophysiology

Hipertrofia benigna de próstata : cáncer de próstata : proceso asistencial integrado. 3ª ed

Publicado en la página web de la Consejería de Salud y Bienestar Social: www.juntadeandalucia.es/salud (Consejería de Salud y Bienestar Social / Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)YesEn Andalucía, y tal y como se establece en el III Plan Andaluz de Salud, se ha definido como una de las líneas prioritarias de actuación la reducción de la morbilidad, mortalidad prematura y discapacidad a través del desarrollo de Planes Integrales y de Procesos Asistenciales Integrados. Teniendo en cuenta que el cáncer de próstata constituye uno de los principales problemas de salud de la población masculina, se ha procedido a la revisión y actualización del documento anterior (año 2005)incorporando nuevos aspectos relacionados con dimensiones específicas de calidad

Telomere-based risk models for the early diagnosis of clinically significant prostate cancer.

The objective of this study was to explore telomere-associated variables (TAV) as complementary biomarkers in the early diagnosis of prostate cancer (PCa), analyzing their application in risk models for significant PCa (Gleason score > 6). As part of a larger prospective longitudinal study of patients with suspicion of PCa undergoing prostate biopsy according to clinical practice, a subgroup of patients (n = 401) with PSA 3-10 ng/ml and no prior biopsies was used to evaluate the contribution of TAV to discern non-significant PCa from significant PCa. The cohort was randomly split for training (2/3) and validation (1/3) of the models. High-throughput quantitative fluorescence in-situ hybridization was used to evaluate TAV in peripheral blood mononucleated cells. Models were generated following principal component analysis and random forest and their utility as risk predictors was evaluated by analyzing their predictive capacity and accuracy, summarized by ROC curves, and their clinical benefit with decision curves analysis. The median age of the patients was 63 years, with a median PSA of 5 ng/ml and a percentage of PCa diagnosis of 40.6% and significant PCa of 19.2%. Two TAV-based risk models were selected (TAV models 1 and 2) with an AUC ≥ 0.83 in the full study cohort, and AUC > 0.76 in the internal validation cohort. Both models showed an improvement in decision capacity when compared to the application of the PCPT-RC in the low-risk probabilities range. In the validation cohort, with TAV models 1 and 2, 33% /48% of biopsies would have been avoided losing 0/10.3% of significant PCa, respectively. The models were also tested and validated on an independent, retrospective, non contemporary cohort. Telomere analysis through TAV should be considered as a new risk-score biomarker with potential to increase the prediction capacity of significant PCa in patients with PSA between 3-10 ng/ml