PSA Derivatives Research Articles

Surveillance after Focal Therapy - a Comprehensive Review.

to date, no standardized, evidence-based follow-up schemes exist for the monitoring of patients who underwent focal therapy (FT) and expert centers rely mainly on their own experience and/or institutional protocols. We aimed to perform a comprehensive review of the most advantageous follow-up strategies and their rationale after FT for prostate cancer (PCa). a narrative review of the literature was conducted to investigate different follow-up protocols of FT for PCa. Outcomes of interest were post-ablation oncological and functional outcomes and complications. Oncological success after FT was generally defined as the biopsy-confirmed absence of clinically significant PCa in the treated zone. De novo PCa in the untreated area usually reflects an inaccurate patient selection and should be treated as primary PCa. During follow-up, oncological outcomes should be evaluated with periodic PSA, multiparametric MRI and prostate biopsy. The use of PSA derivatives and new biomarkers is still controversial and therefore not recommended. The first MRI after FT should be performed between 6-12 months to avoid ablation-related artifacts and diagnostic delay in case of FT failure. Other imaging modalities, such as PSMA PET/CT scan, are promising but still need to be validated in the post-FT setting. A 12-month "for-protocol" prostate biopsy, including targeted and systematic biopsy, was generally considered the preferred biopsy method to rule out tumor persistence/recurrence. Subsequent mpMRIs and biopsies should follow a risk-adapted approach depending on the clinical scenario. Functional outcomes should be periodically assessed using validated questionnaires within the first year, when typically recover to a new baseline. Complications, despite uncommon, should be strictly monitored mainly in the first month. FT follow-up is a multifaceted process involving clinical, radiological, and histological assessment. Studies evaluating the impact of different follow-up strategies and ideal timings are needed to produce standardized protocols following FT.

The anticorrosive efficacy of newly synthesized pyrido-bis(benzo[b]azoninone) analogs on carbon steel under sweet corrosive environments: A combined empirical and theoretical approaches

This study presents a novel and eco-friendly approach to address the critical challenge of carbon steel corrosion in CO2-rich saline environments, a significant concern in the oil and gas industry. We report the efficient synthesis of a new class of corrosion inhibitors: pyrido-bis(benzo[b]azoninone) (PSA) analogs. These PSA derivatives were conveniently prepared using a one-pot, three-component reaction under microwave irradiation, with their chemical structures confirmed by 1H and 13C NMR spectroscopy. The effectiveness of the synthesized PSA derivatives was then evaluated for their ability to protect N80 steel in a CO2-saturated 3.5 % NaCl solution. The results were impressive, with the PSA demonstrating outstanding corrosion inhibition efficiencies ranging from 94.6 % to 96.2 %. Electrochemical measurements (potentiodynamic polarization and electrochemical impedance spectroscopy) revealed that the PSAs act as mixed-type inhibitors, adhering to the Langmuir adsorption isotherm on the steel surface. X-ray photoelectron spectroscopy (XPS) analysis provided further evidence, confirming the formation of a protective barrier on the steel by the adsorbed PSA. Theoretical support for these findings comes from density functional theory (DFT) calculations, which establish a connection between the theoretical predictions and experimental observations. Additionally, MC simulations further corroborated the effectiveness of PSA adsorption on the iron (110) surface. In conclusion, this research offers groundbreaking insights into developing exceptionally efficient and eco-friendly corrosion inhibitors using novel PSA analogs. This approach holds significant promise for mitigating the challenges the oil and gas industry faces in protecting steel infrastructure in harsh CO2-rich environments.

Investigation of the relationship between endothelial nitric oxide synthase T786C polymorphism and PSA, PSA derivatives, and prostate cancer in the Turkish population.

Prostate cancer is a slowly progressing cancer. However, it has remained a major medical problem for affected men. Risk factors of prostate cancer include age, race, and prostate cancer family history. Prostate cancer may occur at different frequencies between ethnic populations and countries. Currently, studies on genetic risk factors in prostate cancer aetiology have been increasing. Due to the importance of changes in endothelial nitric oxide synthase in carcinogenesis, we aimed to reveal whether eNOS T786C polymorphism is associated with prostate cancer. Archival samples included in this study were whole blood samples taken from patients who were grouped according to prostate biopsy pathology results (BPH, n: 42; PCa, n: 48) and from healthy participants (controls, n:27). DNA was isolated from these whole blood samples and real-time polymerase chain reaction analysis was performed for endothelial nitric oxide synthase T786C polymorphism with LightCycler 480 II. Measured free and total prostate-specific antigen serum levels were evaluated retrospectively. There was a statistical difference between patient-healthy control and control-healthy control groups regarding genotype distributions for eNOS T786C hism. Controls were more likely to have TC and CC genotypes and C alleles than the other two groups. Compared to other groups, the percentage of the eNOS786C allele in the control group was found to be higher. As a result of these data, it can be thought that carrying the allele may be protective against the disease.

Digital rectal examination impact on PSA derivatives and prostate biopsy triggers: a contemporary study.

To evaluate the impact of the digital rectal exam (DRE) on PSA measurements and clinical decision-making. Healthy male volunteers between 50 and 70years old were recruited during a 30-day public screening program. PSA levels were measured using two different methods (standard enhanced chemiluminescence immunoassay-ECLIA, and novel immunochromatography assay-ICA/rapid PSA) in the same blood sample. Two blood samples were drawn; first before DRE and the second 30-40min after DRE. The effect of DRE on PSA levels and its impact on clinical decision-making for individual patients were evaluated based on different biopsy trigger cutoffs. ECLIA-PSA was measured in 74 participants both pre- and 37 ± 5min post-DRE, mean age 57.2 ± 8.3years, and mean prostate volume 33.6 (20-80) cm3. Both total and free ECLIA-PSA increased significantly after DRE (mean increase of 0.47 and 0.26ng/ml, respectively, both p < 0.001). Different internationally accepted biopsy triggers were reached after DRE only: 5 total PSA > 3ng/ml, 13 increase > 0.75ng/ml, 3 PSA density > 0.15, and 1 free/total PSA < 0.18. On two occasions, patients were pushed away from biopsy trigger after DRE due to free/total PSA > 0.18. ICA-PSA was detectable (> 2.0ng/ml) in 5 of 45 measured samples (11%) before DRE and 13/45 (29%) after DRE, p = 0.0316. Four among five detectable ICA-PSA tests increased after DRE. Performing DRE immediately before PSA measurement might change the clinical decision-making on a significant number of occasions (roughly 1 in 3); even though the mean increase (0.47ng/ml) looks deceivingly small. Further studies are required that include gold standard tests (biopsy, or imaging).

Multivariable Models Incorporating Multiparametric Magnetic Resonance Imaging Efficiently Predict Results of Prostate Biopsy and Reduce Unnecessary Biopsy.

PurposeWe sought to develop diagnostic models incorporating mpMRI examination to identify PCa (Gleason score≥3+3) and CSPCa (Gleason score≥3+4) to reduce overdiagnosis and overtreatment.MethodsWe retrospectively identified 784 patients according to inclusion criteria between 2016 and 2020. The cohort was split into a training cohort of 548 (70%) patients and a validation cohort of 236 (30%) patients. Age, PSA derivatives, prostate volume, and mpMRI parameters were assessed as predictors for PCa and CSPCa. The multivariable models based on clinical parameters were evaluated using area under the curve (AUC), calibration plots, and decision curve analysis (DCA).ResultsUnivariate analysis showed that age, tPSA, PSAD, prostate volume, MRI-PCa, MRI-seminal vesicle invasion, and MRI-lymph node invasion were significant predictors for both PCa and CSPCa (each p≤0.001). PSAD has the highest diagnostic accuracy in predicting PCa (AUC=0.79) and CSPCa (AUC=0.79). The multivariable models for PCa (AUC=0.92, 95% CI: 0.88–0.96) and CSPCa (AUC=0.95, 95% CI: 0.92–0.97) were significantly higher than the combination of derivatives for PSA (p=0.041 and 0.009 for PCa and CSPCa, respectively) or mpMRI (each p<0.001) in diagnostic accuracy. And the multivariable models for PCa and CSPCa illustrated better calibration and substantial improvement in DCA at threshold above 10%, compared with PSA or mpMRI derivatives. The PCa model with a 30% cutoff or CSPCa model with a 20% cutoff could spare the number of biopsies by 53%, and avoid the number of benign biopsies over 80%, while keeping a 95% sensitivity for detecting CSPCa.ConclusionOur multivariable models could reduce unnecessary biopsy without comprising the ability to diagnose CSPCa. Further prospective validation is required.

PD53-12 THE PROSTATE HEALTH INDEX IMPROVES PREDICTIVE VALUE IN PATIENTS WITH PI-RADS 3 LESIONS

INTRODUCTION AND OBJECTIVE: Major technical improvements in multiparametric MRI (mpMRI) of prostate with the standard approach to interpretation using the PI-RADS v2 offers reliable visualization of potentially clinically significant prostate cancer (csPca) and thus has shown advantages as a means by which to better select patients for biopsy and facilitate direct targeting of lesions during biopsy.However, currently available data show that the actual prevalence of csPCa after targeted biopsy in PI-RADS 3 lesions vary from 16% to 21%. We hypothesize that biomarkers such as PHI may better stratify a higher risk subgroup that harbor csPCa in patients with PI-RADS 3 lesions. METHODS: Patients with at least one PI-RADS = 3 lesion on mpMRI were enrolled for cognitive MRI-TRUS fusion-targeted prostate biopsy. All these patients had either PSA greater than 4 ng/ml and/or suspicious digital rectal examination (DRE) and/or previous negative systematic transrectal ultrasound (TRUS) prostate biopsy. All patients had received PHI test before the prostate biopsy. AUC under the ROC curves were estimated for the various PSA derivatives, along with the specificity at a pre-specified sensitivity of 90%. RESULTS: As PI-RADS 3 lesions have relatively low rates of csPCa and may present a new “grey zone” cognitive MRI-TRUS fusion-targeted prostate biopsy. Adding PHI to mpMRI improved predictive performance for overall PCa (AUC 0.818, CI 0.702-0.934) and csPCa detection (AUC 0.881, CI 0.787-0.975). The PHI alone was a significant predictor for any cancer (OR 5.95, 95% CI 1.35–42.36, p = 0.026) and significant cancers (OR 12.41, 95% CI 3.06–28.4, p < 0.001) after adjusting for age, prostate volume, previous negative biopsy and abnormal DRE in logistic regression. We found the optimal cutoff to be ≥ 39.7 which would allow 39.3 % of patients to avoid biopsy. At this level, no csPCa was missed and both sensitivity and NPV were 100%. CONCLUSIONS: In patients with PI-RADS 3 index lesions, which is a gray zone for PI-RADS v2, PHI exhibits outstanding performance in predicting csPCa. Using a PHI cutoff of ≥ 39.7, up to 39 % of prostate biopsy could be avoided in patients with PI-RADS 3 lesions and no csPCa will be missed.Source of Funding: nil

Preoperative %p2PSA and Prostate Health Index Predict Pathological Outcomes in Patients with Prostate Cancer Undergoing Radical Prostatectomy

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

PD35-11 PSA DENSITY PERFORMS BETTER IN CAUCASIAN MEN THAN IN AFRICAN AMERICAN MEN IN PREDICTING PROSTATE CANCER AND SIGNIFICANT CANCER ON PROSTATE BIOPSY

INTRODUCTION AND OBJECTIVES:PSA density (PSAD) is a PSA derivative that has been used to help predict for prostate cancer on biopsy. PSAD cut offs were formulated from cohorts consisting of mostly ...

Abstract 3595: A panel of serum proteins, metabolite and lipid for prognosing prostate cancer progression

Abstract Background: Predicting the clinical course of prostate cancer is challenging due to the wide biological spectrum of the disease. The limited prognostic value of pretreatment PSA, grade, and clinical stage prompted discoveries of early biomarkers for predicting the clinical course of the disease. Along these lines new biomarkers have been developed including pre-diagnostic urine-based tests, serum-based assays for PSA derivatives, and diagnostic biopsy tissue-based assays. Although these advancements continue to improve early diagnosis and prognosis there is a need for further developments to complement current prognostic approaches. While most of the prostate cancer detection and prognostic approaches have been developed by using one type of analyte, e.g. mRNA/DNA or proteins, or metabolites, some also include combination of multiple types of analytes. Indeed, development of prognostic panels that include multiple type of analytes requires sensitive and reproducible detection methods and advanced bioinformatic platforms. The objective of our study was to discover prostate cancer prognostic markers employing an advanced multi-analyte discovery platform. Methods: Pre-surgery serum samples were evaluated among a longitudinally followed (median 10 years), racially diverse prostate cancer patient group (N=385) by mass spectrometry, integrating proteomic, metabolomic and lipidomic (multi-omics) data to differentiate disease progression-free patients (N=310) from patients with disease progression (N=75) by using the Bayesian computational approach. Results: Integrated disease progression data with multi-omics profiles have identified the combined predictive performance of two proteins, a metabolite and a phospholipid molecular species with a cumulative performance of AUC= 0.782 for differentiating patient groups with disease progression-free survival from the group of patients with progression. This panel demonstrated a 0.94 negative predictive value with a modest positive predictive value of 0.34. The odds ratio of disease progression was 6.56 (2.98, 14.40) with the panel of markers. Conclusions: We have identified a panel of multi-analytes with promising performance in predicting disease progression-free survival of prostate cancer patients by evaluating pre-surgery serum samples. This panel offers new opportunities complementing current prognostic markers with potential impact on primary treatment and follow up strategies. Citation Format: Michael Kiebish, Jennifer Cullen, Amina Ali, Leonardo O. Rodrigues, Emily Y. Chen, Eric Milliman, Lixia Xang, Vladimir Tolstikov, Fei Gao, Kiki Panagopoulos, Jeonifer Garren, Yongmei Chen, Gyorgy Petrovics, Inger L. Rosner, Isabell A. Sesterhenn, David McLeod, Elder Granger, Rangaprasad Sarangarajan, Alagarsamy Srinivasan, Viatcheslav Akmaev, Albert Dobi, Niven Narain, Shiv Srivastava. A panel of serum proteins, metabolite and lipid for prognosing prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3595.

Combining Prostate Health Index density, magnetic resonance imaging and prior negative biopsy status to improve the detection of clinically significant prostate cancer.

To determine the performance of Prostate Health Index (PHI) density (PHID) combined with MRI and prior negative biopsy (PNB) status for the diagnosis of clinically significant prostate cancer (PCa). Patients without a prior diagnosis of PCa, with elevated prostate-specific antigen and a normal digital rectal examination who underwent PHI testing prospectively prior to prostate biopsy were included in this study. PHID was calculated retrospectively using prostate volume derived from transrectal ultrasonography at biopsy. Univariable and multivariable logistic regression modelling, along with receiver-operating characteristic (ROC) curve analysis, was used to determine the ability of serum biomarkers to predict clinically significant PCa (defined as either grade group [GG] ≥2 disease or GG1 PCa detected in >2 cores or >50% of any one core) on biopsy. Age, PNB status and Prostate Imaging Reporting and Data System (PI-RADS) score were incorporated into the regression models. Of the 241 men who qualified for the study, 91 (37.8%) had clinically significant PCa on biopsy. The median (interquartile range) PHID was 0.74 (0.44-1.24); it was 1.18 (0.77-1.83) and 0.55 (0.38-0.89) in those with and without clinically significant PCa on biopsy, respectively (P < 0.001). On univariable logistic regression, age and PNB status were associated with clinically significant cancer. Of the tested biomarkers, PHID demonstrated the highest discriminative ability for clinically significant disease (area under the ROC curve [AUC] 0.78 for the univariable model). That continued to be the case in multivariable logistic regression models incorporating age and PNB status (AUC 0.82). At a threshold of 0.44, representing the 25th percentile of PHID in the cohort, PHID was 92.3% sensitive and 35.3% specific for clinically significant PCa; the sensitivity and specificity were 93.0% and 32.4% and 97.4% and 29.1% for GG ≥2 and GG ≥3 disease, respectively. In the 104 men who underwent MRI, PI-RADS score was complementary to PHID, with a PI-RADS score ≥3 or, if PI-RADS score ≤2, a PHID ≥0.44, detecting 100% of clinically significant disease. For that subgroup, of the biomarkers tested, PHID (AUC 0.90) demonstrated the highest discriminative ability for clinically significant disease on multivariable logistic regression incorporating age, PNB status and PI-RADS score. In this contemporary cohort of men undergoing prostate biopsy for the diagnosis of PCa, PHID outperformed PHI and other PSA derivatives in the diagnosis of clinically significant cancer. Incorporating age, PNB status and PI-RADS score led to even further gains in the diagnostic performance of PHID. Furthermore, PI-RADS score was found to be complementary to PHID. Using 0.44 as a threshold for PHID, 35.3% of unnecessary biopsies could have been avoided at the cost of missing 7.7% of clinically significant cancers. Despite these encouraging results, prospective validation is needed.

Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

ObjectivesTo address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort.ResultsUsing published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume <0.5 cm3. Variability across race/ethnicity was found in the univariable analysis for all PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014).Materials and MethodsWe retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3.ConclusionsIncreasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives’ ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice.

BACKGROUNDThe Prostate Health Index (phi) outperforms PSA and other PSA derivatives for the diagnosis of prostate cancer (PCa). The impact of phi testing in the real-world clinical setting has not been previously assessed.METHODSIn a single, large, academic center, phi was tested in 345 patients presenting for diagnostic evaluation for PCa. Findings on prostate biopsy (including Grade Group [GG], defined as GG1: Gleason score [GS] 6, GG2: GS 3+4=7, GG3: GS 4+3=7, GG4: GS 8, and GG5: GS 9-10), magnetic resonance imaging (MRI), and radical prostatectomy (RP) were prospectively recorded. Biopsy rates and outcomes were compared to a contemporary cohort that did not undergo phi testing (n=1318).RESULTSOverall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only 3 men with phi<27 had cancer of GG≥2. Phi was superior to PSA for the prediction of any PCa (AUC 0.72 vs. 0.47) and GG≥2 PCa (AUC 0.77 vs. 0.53) on prostate biopsy. Among men undergoing MRI and phi, no men with phi<27 and PI-RADS≤3 had GG≥2 cancer. For those men proceeding to RP, increasing phi was associated with higher pathologic GG (p=0.002) and stage (p=0.001). Compared to patients who did not undergo phi testing, the use of phi was associated with a 9% reduction in the rate of prostate biopsy (39% vs. 48%; p<0.001). Importantly, the reduction in biopsy among the phi population was secondary to decreased incidence of negative (8%) and GG1 (1%) biopsies, while the proportion of biopsies detecting GG≥2 cancers remained unchanged.CONCLUSIONSIn this large, real-time clinical experience, phi outperformed PSA alone, was associated with high-grade PCa, and provided complementary information to MRI. Incorporation of phi into clinical practice reduced the rate of unnecessary biopsies without changing the frequency of detection of higher grade cancers.

Performance of the Prostate Health Index in predicting prostate biopsy outcomes among men with a negative digital rectal examination and transrectal ultrasonography.

The [-2]proPSA (p2PSA) and its derivatives, the p2PSA-to-free PSA ratio (%p2PSA), and the Prostate Health Index (PHI) have greatly improved discrimination between men with and without prostate cancer (PCa) in prostate biopsies. However, little is known about their performance in cases where a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are negative. A prospective cohort of 261 consecutive patients in China with negative DRE and TRUS were recruited and underwent prostate biopsies. A serum sample had collected before the biopsy was used to measure various PSA derivatives, including total prostate-specific antigen (tPSA), free PSA, and p2PSA. For each patient, the free-to-total PSA ratio (%fPSA), PSA density (PSAD), p2PSA-to-free PSA ratio (%p2PSA), and PHI were calculated. Discriminative performance was assessed using the area under the receiver operating characteristic curve (AUC) and the biopsy rate at 91% sensitivity. The AUC scores within the entire cohort with respect to age, tPSA, %fPSA, PSAD, p2PSA, %p2PSA, and PHI were 0.598, 0.751, 0.646, 0.789, 0.814, 0.808, and 0.853, respectively. PHI was the best predictor of prostate biopsy results, especially in patients with a tPSA of 10.1–20 ng ml−1. Compared with other markers, at a sensitivity of 91%, PHI was the most useful for determining which men did not need to undergo biopsy, thereby avoiding unnecessary procedures. The use of PHI could improve the accuracy of PCa detection by predicting prostate biopsy outcomes among men with a negative DRE and TRUS in China.

Clinical utility of prostate-specific antigen mass ratio for prediction of prostate cancer detection on a repeated prostate biopsy.

To assess the clinical utility of the prostate-specific antigen mass ratio (PSA- MR), a newly developed PSA derivative, simply defined as the (i) PSA density (PSA-D) multiplied by the plasma volume or (ii) total PSA amount in circulation per prostate volume, for predicting prostate cancer (PCa) among men undergoing repeated prostate biopsy (PBx). Patients (n = 286), who underwent a repeated PBx, were analyzed. The various parameters associated with PCa detection were noted in each patient. PSA-MR was also calculated. PCa was detected in 63 (22.0%) of 286 patients. PSA-MR was the independent predictor in the univariate- and multivariate logistic regression analyses (OR = 3.448, p = 0.001 and OR = 13.430, p = 0.033, respectively). A nomogram that incorporated PSA-MR was considered a useful tool (predictive accuracy: 79.2%, 95% CI: 0.726-0.858, p < 0.001). Furthermore, a nomogram that incorporated PSA-MR would have avoided 59.6% of unnecessary repeated PBx. The predictive accuracy of PSA-MR was also superior to that of PSA or PSA-D (p = 0.013 and 0.009, respectively). PSA-MR was an independent predictor, and its consideration would have avoided 59.6% of unnecessary repeated PBx for PCa detection. PSA-MR was also superior than PSA or PSA-D. Our results support the use of PSA-MR to facilitate counseling with patients after a negative initial PBx, and use of PSA-MR might reduce further unnecessary biopsies.

5ARI and PSA: evidences

The 5alpha-reductase inhibitors (5ARIs) represent a valid therapeutic option in the long-term treatment of benign prostatic hyperplasia (BPH). One of the most debated topics is the interpretation of the variation of the serum PSA during treatment with 5ARIs. The objective of this review was to analyze the change in serum PSA levels over time and to evaluate its sensitivity and specificity in the screening for prostate cancer (CaP) during treatment. An extensive search using PubMed and Scopus was performed including the following key words: "5ARI", "finasteride", "dutasteride", "prostate cancer", "benign prostatic hyperplasia", "PSA", "kinetics", "PSA derivatives". The reduction of serum PSA during treatment with 5ARIs can be observed up to 48 months after the beginning of the therapy. This category of drugs seems to improve the diagnostic performance of PSA in screening CaP. On the other hand, there is a reduction of the diagnosis of indolent cancers. Any increase in PSA from nadir should be considered suspicious for malignancy. However, if the choice of a biopsy depended only on an increase of the values of serum PSA, a variable percentage of potentially aggressive tumors could not be diagnosed. Therefore, it is important to consider in the clinical and diagnostic follow-up other factors such as digital rectal examination, age, family history of CaP and imaging techniques. 5-ARIs have a positive impact on the specificity of PSA but they must not be the only tool that can identify CaPs with poor prognosis.

EP-1833: Effect of PsA derivatives on DNMT inhibition and radiosensitization in U373MG glioblastoma cell line

EP-1833: Effect of PsA derivatives on DNMT inhibition and radiosensitization in U373MG glioblastoma cell line

2217 VALIDATION OF PSA FREE TO TOTAL RATIO AND PSA DENSITY AGAINST TEMPLATE BIOPSIES OF PROSTATE

You have accessJournal of UrologyProstate Cancer: Detection & Screening (V)1 Apr 20132217 VALIDATION OF PSA FREE TO TOTAL RATIO AND PSA DENSITY AGAINST TEMPLATE BIOPSIES OF PROSTATE Amr Emara, Rebecca Maiti, Simon Bott, Shahid Khan, Tim Nedas, and Richard Hindley Amr EmaraAmr Emara Frimley, United Kingdom More articles by this author , Rebecca MaitiRebecca Maiti United Kingdom More articles by this author , Simon BottSimon Bott Frimley, United Kingdom More articles by this author , Shahid KhanShahid Khan Basingstoke, United Kingdom More articles by this author , Tim NedasTim Nedas Basingstoke, United Kingdom More articles by this author , and Richard HindleyRichard Hindley Basingstoke, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2126AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Transperineal template biopsies (TTP) of the prostate is a well established technique in many centres for various diagnostic, risk stratification and surveillance protocols in the management of localized prostate cancer. Several studies have proven higher cancer detection rate in correlation with elevated levels of PSA in comparison to the previous standard TRUS guided biopsies. In our study we have looked at the predictive value of PSA derivatives in relation to TTP. METHODS Since 2007 we had performed over 400 transperineal template biopsies for different indications based on the national institute of clinical excellence (NICE) recommendations including suspected cancer with negative or inconclusive previous TRUS biopsies, as part of surveillance protocol or more recently mapping to determine the location and extent of prostate cancer as a guide to focal treatment. For those patients who had PSA of 15 μgm/L or less we had free to total PSA ratio and PSA density recorded, we managed to retrospectively collect the data for 145 patients with the above criteria. RESULTS Average age was 64.5 years with Mean PSA 8.9 and clinical stage ranging T1c-T2b. Cancer detection rate for the whole cohort with diagnostic indications was 61.7% (79/128) after excluding those on surveillance protocol and mapping purposes. PSA Free to total (F/T) ratio less than 18% has shown positive predictive value (PPV) of 70% while negative predictive value (NPP) of 65%. As for PSA density more than 0.15 proved PPV of 74.3% and NPP of 50.8%. CONCLUSIONS With proven better sensitivity of the transperineal biopsies in cancer detection we have managed to illustrate that both free to total PSA ratio and PSA density are still holding reasonable predictive values to help in patient counselling for TTP keeping with the previously suggested significance proved against TRUS guided biopsies. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e909 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amr Emara Frimley, United Kingdom More articles by this author Rebecca Maiti United Kingdom More articles by this author Simon Bott Frimley, United Kingdom More articles by this author Shahid Khan Basingstoke, United Kingdom More articles by this author Tim Nedas Basingstoke, United Kingdom More articles by this author Richard Hindley Basingstoke, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comment sélectionner au mieux les candidats aux biopsies de prostate ? Rôle des outils traditionnels et apport des nouveaux marqueurs du cancer de la prostate

In 2010, early detection of prostate cancer continues to rely on digital rectal examination and serum total PSA. However, selecting patients for prostate biopsy requires taking into account the prostate volume and the evolution of PSA over time. PSA derivatives such as PSA density, PSA velocity and the ratio free PSA / total PSA are useful supplements. However, the choice of the threshold value is not well defined and depends on the relative sensitivity and specificity desired. The real innovations come from basic research that has found potential markers of aggressiveness of prostate cancer and molecular biology tools used routinely as the PCA-3 score and the pro-PSA. The role of these new markers for diagnosis and prognosis of prostate cancer remains unclear.

1736 COMPLETE SPINAL CORD LESIONS DECREASE PROSTATE SIZE WITHOUT CHANGING SERUM PSA LEVELS. ARE FREE PSA AND PSA DERIVATIVES AFFECTED?

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Epidemiology and Natural History/Evaluation and Markers1 Apr 20111736 COMPLETE SPINAL CORD LESIONS DECREASE PROSTATE SIZE WITHOUT CHANGING SERUM PSA LEVELS. ARE FREE PSA AND PSA DERIVATIVES AFFECTED? Cevdet Serkan Gökkaya, Çetin Volkan Öztekin, Özgür Demirdal, Nilüfer Kutay Gökkaya, Cüneyt Özden, Halil Uçan, and Ali Memis Cevdet Serkan GökkayaCevdet Serkan Gökkaya Ankara, Turkey More articles by this author , Çetin Volkan ÖztekinÇetin Volkan Öztekin Ankara, Turkey More articles by this author , Özgür DemirdalÖzgür Demirdal Ankara, Turkey More articles by this author , Nilüfer Kutay GökkayaNilüfer Kutay Gökkaya Ankara, Turkey More articles by this author , Cüneyt ÖzdenCüneyt Özden Ankara, Turkey More articles by this author , Halil UçanHalil Uçan Ankara, Turkey More articles by this author , and Ali MemisAli Memis Ankara, Turkey More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.2007AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The effects of spinal cord injury (SCI) on male genital anatomy and function has been of interest during the last two decades, mainly derived by fertility and sexual problems encountered by the referred patient population. Today PSA is still the most frequently used tool in prostate cancer (CaP) diagnosis. Although there are numerous reports about the effects of SCI on PSA levels, the results are controversial and a conclusion is yet to be achieved. Results of the studies regarding prostate volume (Vp) of SCI patients are also controversial. Free to total PSA ratio (f/tPSA) and PSA density (PSAD) are the two PSA derivatives used in conjunct with total serum PSA, in order to increase the sensitivity and specifity of serum PSA when serum PSA is in so called “gray zone”. To our knowledge, there are no data in the literature regarding fPSA, f/tPSA and PSAD levels in SCI patients. The effects of complete SCI on Vp, PSA, fPSA, f/tPSA and PSAD were evaluated in this study. METHODS 35 SCI patients and 35 controls were evaluated for the study. 27 complete SCI patients and 32 age-matched outpatient able-bodied controls were included in the analysis. Vp was measured on transrectal ultrasound, PSA, fPSA, FSH, LH and total and free testosterone levels were obtained and f/tPSA and PSAD were calculated for all patients. RESULTS Mean patient age was 44.26±6.9 years. Mean Vp of the SCI group was significantly lower than controls (19.30±6.88 vs 26.96±8.79, p=0.001) while mean serum PSA, FSH, LH, total and free testosterone of the two groups were similar (p>0.05). Mean fPSA and f/tPSA were significantly lower (0.16±0.096 vs 0.28±0.18, p<0.001 and 0.20±0.18 vs 0.28±0.13, p=0.002, respectively) and PSAD was higher (0.056±0.027 vs 0.043±0.035, p=0.014) than those of the controls. CONCLUSIONS Complete SCI causes lower Vp independent from pituitary-gonadal axis without changing serum PSA when compared to controls. Free PSA, f/tPSA and PSAD are also affected suggesting evaluation of the contemporary CaP diagnosis strategies in patients with SCI. Characteristics of SCI patients and able-bodied controls. Complete SCI (n=25) Control (n=32) P Age (Years) 44.88±7.48 43.78±6.94 0.55 Vp (ml) 19.30±6.88 26.96±8.79 0.001⁎ PSA (ng/ml) 1.05±0.56 1.09±0.73 0.816 fPSA (ng/ml) 0.16±0.096 0.28±0.18 <0.001⁎⁎ f/tPSA 0.20±0.18 0.28±0.13 0.002⁎⁎ PSAD 0.056±0.027 0.043±0.035 0.014⁎⁎ T (ng/ml) 3.78±1.35 3.87±1.43 0.981 fT (pg/ml) 9.27±4.26 9.30±3.74 0.917 FSH (mIU/ml) 7.6±5.9 6.59±4.35 0.994 LH (mIU/ml) 4.59±3.50 4.47±2.27 0.541 ⁎ T-Test, ⁎⁎ Mann-Whitney U Test. Vp: Prostate volume, fPSA: Free PSA, f/tPSA: free to total PSA, PSAD: PSA density, T: Testosterone, fT: free testoeterone. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e697 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cevdet Serkan Gökkaya Ankara, Turkey More articles by this author Çetin Volkan Öztekin Ankara, Turkey More articles by this author Özgür Demirdal Ankara, Turkey More articles by this author Nilüfer Kutay Gökkaya Ankara, Turkey More articles by this author Cüneyt Özden Ankara, Turkey More articles by this author Halil Uçan Ankara, Turkey More articles by this author Ali Memis Ankara, Turkey More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Does the criterion for prostate biopsy indication impact its accuracy? A prospective population-based outpatient clinical setting study

IntroductionProstate specific antigen (PSA) and digital rectal examination (DRE) are the main tests for initial prostate investigation; there is no consensus about the best criterion for prostate biopsies. We aim to check the accuracy of different criteria in this context including PSA derivatives to detect prostate cancer. Material and methodsFour different criteria for indication of prostate biopsy were compared: (A) PSA-density (>15ng/mL/cc); (B) PSA>2.5ng/mL; (C) PSA-velocity (>0.7ng/mL/year); (D) free/total PSA ratio (<15%). All biopsies and histopathological examinations were performed by the same urologist and pathologist, respectively. ResultsThe study was performed on 180 consecutive biopsies with 37.7% overall cancer detection rate: 29 (16.1%) performed following criterion A, 42 (23.3%) criterion B, 65 (36.1%) criterion C and 44 (24.4%) criterion D. Based on PSA criteria alone, the predictive positive value (PPV) was 37.9% for criterion A, 33.3% for B, 32.3% for C and 50.0% for criterion D, respectively, (p>0.05). Associating positive DRE with changed PSA, the PPV increased to 50%, 50%, 43.9% and 68.2% for criteria A, B, C and D, respectively (p>0.05). In univariate analysis, DRE (positive versus negative), PSA level (>10ng/mL versus <4.0ng/mL), free/total PSA ratio (<10% versus >15%) and age were associated with PC. In multivariate analysis only positive DRE was associated with prostate cancer. ConclusionsAll the criteria of PSA derivatives are complementary and useful predictors of cancer risk. However, a positive DRE increased the PPV of PSA derivatives. New tools are needed to improve the accuracy of prostate cancer detection.