Serum Prostate-specific Antigen Testing Research Articles

The Long-Term Impact of 5-alpha Reductase Inhibitors on the Development of Bladder Cancer and the Need for Radical Cystectomy: A Nationwide Observational Study.

To investigate the long-term effects of taking 5-alpha reductase inhibitors (5ARIs) on the development of bladder cancer (BC) and the implementation of radical cystectomy (RC), a standard procedure for advanced BC. From the National Health Insurance Sharing Service database, males aged over 40 years who underwent serum prostate-specific antigen testing from 2006 through 2017 were identified, which is required for the prescription of 5ARIs. The association between the administration duration of 5ARIs and the practice for BC was analyzed. Of the 3,843,968 subjects, 1,514,713 (39.4%) took 5ARIs for an average of 1.53 years, remaining 2,329,255 (60.6%) as non-5ARI counterparts. The incidence of BC was higher in the non-5ARI than in the 5ARI group (1.25% vs. 0.87%, p<0.001), as was the implementation rate of RC (11.1% vs. 10.4%, p=0.037). In a multivariate analysis, the non-5ARI group had a significant risk of BC (hazard ratio [HR]=2.289, 95% confidence interval [CI]=2.241-2.338) and RC (HR=2.199, 95% CI=2.061-2.348) than the 5ARI group. Among the 5ARIs group, though the incidence of BC was maintained (slope=-0.002 per year, p=0.79) after an initial increase for two years, the rate of RC decreased (slope=-1.1, p<0.001) consistently for ten years during the administration. Compared to the untreated group, 5ARIs use was associated with lower rates of BC and RC. In contrast to the increase in BC seen with short-term use of less than two years, long-term use of 5ARIs decreased the rate of RC in a duration-dependent manner for ten years, suggesting a strategy to prevent disease progression.

Screening history and risk of death from prostate cancer: a nested case–control study within the screening arm of the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC)

PurposeWe assessed the risk of death from prostate cancer (PCa) in relation to men’s screening histories, i.e., screening attendance among men who were offered screening.MethodsMen in the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC) screening arm were invited to up to three screening rounds with the serum prostate-specific antigen (PSA) test at 4-year intervals during 1996–2007.Case subjects (n = 330) were men who died from PCa. Each case was matched to five controls (n = 1544) among the men who were free of PCa.Screening history was defined as (1) never/ever attended screening prior to the case diagnosis; (2) attended at the first screening round; and (3) recency of screening, calculated as the time from last screening attendance to the date of case diagnosis.The association between screening history and the risk of death from PCa was estimated by odds ratios (OR) with 95% confidence intervals (CI) using conditional logistic regression.ResultsHaving ever attended screening versus never attended was associated with a reduced risk of PCa death (OR 0.60, 95% CI 0.45–0.81) and a similar association was found for those attended (versus not attended) the first screening round (OR 0.67, 95% CI 0.51–0.87).The effect by time since last screen for the risk of PCa death was significantly lower 2–7 years since last screen.ConclusionAmong men invited to screening, subjects who attended any PSA screening during the previous 19 years had a 40% reduction in PCa mortality compared to non-screened men.

Machine learning-based prediction model and visual interpretation for prostate cancer

BackgroundMost prostate cancers(PCa) rely on serum prostate-specific antigen (PSA) testing for biopsy confirmation, but the accuracy needs to be further improved. We need to continue to develop PCa prediction model with high clinical application value.MethodsBenign prostatic hyperplasia (BPH) and prostate cancer data were obtained from the Chinese National Clinical Medical Science Data Center for retrospective analysis. The model was constructed using the XGBoost algorithm, and patients’ age, body mass index (BMI), PSA-related parameters and serum biochemical parameters were used as model variables. Using decision analysis curve (DCA) to evaluate the clinical utility of the models. The shapley additive explanation (SHAP) framework was used to analyze the importance ranking and risk threshold of the variables.ResultsA total of 1915 patients were included in this study, including 823 (43.0%) were BPH patients and 1092 (57.0%) were PCa patients. The XGBoost model provided better performance (AUC 0.82) compared with f/tPSA (AUC 0.75),tPSA (AUC 0.68) and fPSA (AUC 0.61), respectively. Based on SHAP values, f/tPSA was the most important variable, and the top five most important biochemical parameter variables were inorganic phosphorus (P), potassium (K), creatine kinase MB isoenzyme (CKMB), low-density lipoprotein cholesterol (LDL-C), and creatinine (Cre). PCa risk thresholds for these risk markers were f/tPSA (0.13), P (1.29 mmol/L), K (4.29 mmol/L), CKMB ( 11.6U/L), LDL-C (3.05mmol/L) and Cre (74.5-99.1umol/L).ConclusionThe present model has advantages of wide-spread availability and high net benefit, especially for underdeveloped countries and regions. Furthermore, these risk thresholds can assist in the diagnosis and screening of prostate cancer in clinical practice.

Impact of Physical Activity on Prostate Cancer Incidence

Prostate cancer is a leading cancer in men, with its incidence varying among different countries and ethnic groups. The introduction of serum prostate-specific antigen (PSA) testing has led to increased early detection rates, particularly in high Human Development Index (HDI) countries. Several extrinsic or modifiable factors have been implicated in the development of prostate cancer. Diet, including high meat and dairy consumption, alcohol intake, and dietary supplements, has shown inconsistent associations. Obesity has emerged as a significant risk factor for prostate cancer and can worsen prognosis and treatment outcomes. Conversely, consumption of fish and fish oil has been associated with a lower incidence and mortality rate of prostate cancer.&#x0D; The relationship between physical activity and prostate cancer risk has been extensively studied, yielding mixed results. While physical activity has consistently shown protective effects against other cancers, its association with prostate cancer risk is less clear. Some studies suggest a potential benefit, particularly with vigorous physical activity, while others find no significant association. However, physical activity has demonstrated positive effects on survival rates and disease progression among men already diagnosed with prostate cancer.

METCAM Is a Potential Biomarker for Predicting the Malignant Propensity of and as a Therapeutic Target for Prostate Cancer.

Prostate cancer is the second leading cause of cancer-related death worldwide. This is because it is still unknown why indolent prostate cancer becomes an aggressive one, though many risk factors for this type of cancer have been suggested. Currently, many diagnostic markers have been suggested for predicting malignant prostatic carcinoma cancer; however, only a few, such as PSA (prostate-specific antigen), Prostate Health Index (PHI), and PCA3, have been approved by the FDA. However, each biomarker has its merits as well as shortcomings. The serum PSA test is incapable of differentiating prostate cancer from BPH and also has an about 25% false-positive prediction rate for the malignant status of cancer. The PHI test has the potential to replace the PSA test for the discrimination of BPH from prostate cancer and for the prediction of high-grade cancer avoiding unnecessary biopsies; however, the free form of PSA is unstable and expensive. PCA3 is not associated with locally advanced disease and is limited in terms of its prediction of aggressive cancer. Currently, several urine biomarkers have shown high potential in terms of being used to replace circulating biomarkers, which require a more invasive method of sample collection, such as via serum. Currently, the combined multiple tumor biomarkers may turn out to be a major trend in the diagnosis and assessment of the treatment effectiveness of prostate cancer. Thus, there is still a need to search for more novel biomarkers to develop a perfect cocktail, which consists of multiple biomarkers, in order to predict malignant prostate cancer and follow the efficacy of the treatment. We have discovered that METCAM, a cell adhesion molecule in the Ig-like superfamily, has great potential regarding its use as a biomarker for differentiating prostate cancer from BPH, predicting the malignant propensity of prostate cancer at the early premalignant stage, and differentiating indolent prostate cancers from aggressive cancers. Since METCAM has also been shown to be able to initiate the spread of prostate cancer cell lines to multiple organs, we suggest that it may be used as a therapeutic target for the clinical treatment of patients with malignant prostate cancer.

Population‑based prostate‑specific antigen screening for prostate cancer may have an indirect effect on early detection through opportunistic testing in Kusatsu City, Shiga, Japan.

Prostate cancer is the most common genitourinary cancer in men. Population-based serum prostate-specific antigen (PSA) testing is used to screen men for the early detection of asymptomatic prostate cancer. The present study compared the features of patients with prostate cancer in Kusatsu City, the only municipality in Shiga Prefecture of Japan to implement organized PSA screening, with those in other municipalities. The target population for organized PSA screening by mail invitation was men ≥50 years. Patients were pathologically diagnosed via prostate biopsy because of elevated serum PSA. This multicenter observational study was subsequently conducted in 14 hospitals. The following information was extracted from patient records: age, reason for PSA testing, initial PSA level, Gleason score, clinical stage, and place of residence. Risk classification was defined as low, intermediate, high, and advanced. Each patient was stratified according to their city/town. A total of 984 patients diagnosed with prostate cancer in Shiga in 2012 and 2017 were analyzed, of which 955 (97%) were opportunistically tested, with the remaining 29 (3%) assessed by organized screening. In Kusatsu, 93 patients were diagnosed, of whom 26 (28%) were detected by organized screening. By contrast, only three of 891 patients (0.3%) were detected by organized screening in other municipalities. Of patients in Kusatsu, cases identified by opportunistic testing had a higher initial PSA value (P=0.010) than those identified by organized screening. However, patients detected through opportunistic testing in Kusatsu City were younger (P=0.034), had a lower PSA value (P=0.001), and improved risk classification (P<0.001) than those in other municipalities. It was concluded that more patients were diagnosed with early-stage cancer by organized PSA screening. Furthermore, population-based PSA screening in Kusatsu City may have indirectly affected early detection, even by opportunistic testing.

Circulating metabolite biomarkers: a game changer in the human prostate cancer diagnosis.

Prostate cancer (PCa) is the second most commonly diagnosed cancer in men in Western and Asian countries. Serum prostate-specific antigen (PSA) test has been the routine diagnostic method despite the tremendous research in diagnostic markers for early detection of PCa. A shift towards a promising and potential biomarker for PCa detection is through metabolomic profiling of biofluids, particularly the blood and urine samples. Finding reliable, routinely usable circulating metabolite biomarkers may not be a distant reality. We performed a PubMed-based literature search of metabolite biomarkers in blood and urine for the early detection of prostate cancer. The timeline of these searches was limited between 2007 and 2022 and the following keywords were used: 'metabolomics', 'liquid biopsy', 'circulating metabolites', 'serum metabolite', 'plasma metabolite', and 'urine metabolite' with respect to 'prostate cancer'. We focussed only on diagnosis-based studies with only the subject-relevant articles published in the English language and excluded all of the other irrelevant publications that included prostate tissue biomarkers and cell line biomarkers. We have consolidated all the blood and urine-based potential metabolite candidates in individual as well as panels, including lipid classes, fatty acids, amino acids, and volatile organic compounds which may become useful for PCa diagnosis. All these metabolome findings unveil the impact of different dimensions of PCa development, giving a promising strategy to diagnose the disease since suspected individuals can be subjected to repeated and largescale blood and urine testing.

Utilization of Gonadotropin-Releasing Hormone Agonists in the Treatment of Metastatic and Locally Advanced Prostate Cancer - Comparisons of Practices from Three European Countries

Abstract Introduction: Prostate cancer is one of the most common health threats for men in the developed world. With the advent of prostate cancer screening using serum prostate-specific antigen (PSA) tests, prostate cancer mortality has declined at the expense of substantial disease overtreatment. Modern prostate cancer therapy is performed according to certain guidelines. Antiandrogens are compounds that inhibit the action of androgens in prostate cancer cells by blocking receptors and preventing the binding of hormones to them. Aim: The aim of this research is to analyze the use of registered forms of LHRH agonists used in the treatment of locally advanced and metastatic prostate cancer in the last five years to examine trends in prescribing this group of drugs in Serbia whose patients gravitate towards the Urology Clinic at the UCC Kragujevac. Material and method: Using the ATC/DDD methodology, the use of LHRH agonists at the Urology Clinic of the UCC Kragujevac. A retrospective study of the use of this group of drugs according to the ATC classification was performed on the basis of data obtained from the hospital pharmacy for the period from year 2016 to year 2021, and the results are expressed by the number of DDD per 1000 inhabitants per day (1000/inhabitants/day). In the observed period, 1361 patients with a diagnosis of C61 (malignant prostate tumor) were treated at the Clinic of Urology. Results: In the observed period, a preparation containing triptorelin in a dose sufficient for one month of therapy was most often used. The total consumption of gonadorelin was lower compared to the rest of Serbia and EU countries, which was expected due to the protocol and the number of patients who gravitated towards the UCC Kragujevac. Conclusion: Despite certain limitations, this evaluation represents the first attempt to summarize the available evidence on the prescribing of LHRH agonists in Serbia. It was found that the consumption in UCCKG is lower compared to the consumption of these drugs in Serbia, Croatia and Italy at the same time intervals, for the same observed diagnosis.

The Incidence of Prostate-Specific Antigen Test in a Country With a Limited Social Perception of Prostate Cancer 2006-2016: Disparities Manifested by Residential Area

Purpose: To trace the incidence of serum prostate-specific antigen (PSA) tests by the residential areas of Korea, where social awareness on prostate cancer (PCa) is limited due to the absence of a public screening.Materials and Methods: From Korean national health insurance data, the number of men older than 40 years who performed PSA testing without PCa or before the enrollment on the national registry during 2006–2016 was identified, then its association with the incidence of PCa were analyzed by a residential area categorized into metropolitan, urban, and rural area.Results: PSA testing was performed more in the metropolitan area in 2006–2008, but performed the most prevalently in the rural area since 2010. Among the 17 administrative districts, the most PSA-tested district was Jeollabuk-do (9.36%) in 2016, which was Seoul (2.85%) in 2006. The mean repetition number of PSA tests during 11 years of the study period was highest among the inhabitant of Seoul (3.25 times, p&lt;0.0001), followed by Gwangju (2.98 times), another metropolitan city. The mean repetition number of PSA tests during the study decade was in the order of metropolitan area (2.97 times), rural area (2.83 times), and urban area (2.75 times, p&lt;0.0001). In every year, however, the incidence of PCa was the highest in a rural area, where had the oldest mean age.Conclusions: Despite a recent increase of PSA screening and diagnosis of PCa especially in the rural area, the opportunity of repeated testing was presented more to the inhabitant of a metropolitan area.

The national-wide incidence of prostate-specific antigen testing trend for a decade in Korea by age group.

PurposeTo document nationwide serum prostate-specific antigen (PSA) testing trends over the past decade and to investigate the impact of testing on prostate cancer (PCa) detection.Materials and MethodsUsing annual National Health Insurance Service of Korea data for the period 2006 to 2016, PSA testing rates were investigated for men aged ≥40 years by decade, and associations between test rates and registered PCa cases were analyzed.ResultsDuring the study period, the incidence of PCa increased about threefold (4,415 in 2006 to 15,046 in 2016). PCa incidences increased with age (p<0.001) and about 60% of cases were over 70 years old. Despite a fourfold increase in PSA testing (246,911 in 2006 to 937,548 in 2016), the average exposure rate among all men was only 7.27% in 2016, and the mean number of repeat tests for those that did not develop PCa during the study period was 2.9. PSA test rates increased with age and in 2016 were 1.65% for those in their 40s, 4.90% for those in their 50s, 12.0% for those in their 60s, 19.2% for those in their 70s, and 21.6% for those aged ≥80. Regardless of the age groups, a significant association was found between PSA test numbers and the detection of PCas.ConclusionsIn contrast to the soaring incidence of PCa especially in those aged over 70 years who have a more frequent chance for PSA testing triggered by concomitant voiding symptoms, low exposure in general and among relatively younger men favors a countrywide screening policy.

Biomarkers for detection of clinically significant prostate cancer: contemporary clinical data and future directions.

Use of serum prostate-specific antigen (PSA) testing for early detection of prostate cancer appears to reduce cancer-specific mortality. Due to the limited specificity of PSA for clinically significant [Grade Group (GG) ≥2] cancer, however, screening carries substantial risks, including frequent unnecessary prostate biopsies and overdetection of non-aggressive cancers. To that end, serum and urine biomarkers with improved specificity for GG ≥2 cancer have been proposed for clinical use following PSA. In the current article, we present clinical validation data for five such biomarkers: PHI, 4Kscore, SelectMDx, ExoDx, and MPS. For all studies, we specify the study population (overall biopsy referral vs. pre-specified PSA ranges), previous biopsy status (biopsy-naïve vs. previous negative biopsy), and the proportion of subjects diagnosed with GG ≥2 cancer. Outcomes include test performance characteristics: sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Published data were used to compute the number of unnecessary biopsies avoided and number of GG ≥2 cancers missed if the biomarker had been used clinically to select for prostate biopsy. The evidence review is preceded by a primer on these and other clinically-relevant summary statistics.

Development of Parallel Reaction Monitoring Assays for the Detection of Aggressive Prostate Cancer Using Urinary Glycoproteins.

Recently, we have found that two urinary glycoproteins, prostatic acid phosphatase (ACPP) and clusterin (CLU), combined with serum prostate-specific antigen (PSA) can serve as a three-signature panel for detecting aggressive prostate cancer (PCa) based on a quantitative glycoproteomic study. To facilitate the translation of candidates into clinically applicable tests, robust and accurate targeted parallel reaction monitoring (PRM) assays that can be widely adopted in multiple labs were developed in this study. The developed PRM assays for the urinary glycopeptides, FLN*ESYK from ACPP and EDALN*ETR from CLU, demonstrated good repeatability and a sufficient working range covering three to four orders of magnitude, and their performance in differentiating aggressive PCa was assessed by the quantitative analysis of urine specimens collected from 69 nonaggressive (Gleason score = 6) and 73 aggressive (Gleason ≥ 8) PCa patients. When ACPP combined with CLU, the discrimination power was improved from an area under a curve (AUC) of 0.66 to 0.78. By combining ACPP, CLU, and serum PSA to form a three-signature panel, the AUC was further improved to 0.83 (sensitivity: 84.9%, specificity: 66.7%). Since the serum PSA test alone had an AUC of 0.68, our results demonstrated that the new urinary glycopeptide PRM assays can serve as an adjunct to the serum PSA test to achieve better predictive power toward aggressive PCa. In summary, our developed PRM assays for urinary glycopeptides were successfully applied to clinical PCa urine samples with a promising performance in aggressive PCa detection.

Serum Prostate-Specific Antigen Testing for Early Detection of Prostate Cancer: Managing the Gap between Clinical and Laboratory Practice.

Current clinical practice guidelines (CPGs) for early detection of prostate cancer recommend for clinical decision-making a personalized prostate-specific antigen (PSA)-based management to improve the risk-benefit ratio of the screening strategy. Some important critical issues regarding the PSA determination in the clinical framework are, however, still neglected in current guidelines and a major focus of recommendations on those aspects would be needed to improve their effectiveness. Evidence sources in the available literature concerning the interchangeability of total PSA results measured with different commercial methods were critically appraised. We discuss how the heterogeneity of the measurand, the intermethod bias, and the design and selectivity of immunoassays may affect the diagnostic accuracy of selected PSA thresholds, and how knowledge of the analytical characteristics of assays in service, such as the recognized PSA circulating forms and the cross-reactivity with PSA homologs, is basic for improving both clinical decision-making in cancer screening and the reliability of the clinical interpretation of results at the individual level. Current CPGs ignore the poor interchangeability of PSA results obtained from different assays and the substantial role of laboratory issues in clinical performance of PSA testing. Involved stakeholders should contribute to fill the existing gap by: (a) preparing commutable reference materials for immunoassay calibration; (b) providing analytical characteristics that may explain the different performance of assays; (c) deriving outcome-based analytical performance specifications for PSA measurement; and (d) giving more focus on laboratory items when CPGs are prepared.

Commercialized Blood-, Urinary- and Tissue-Based Biomarker Tests for Prostate Cancer Diagnosis and Prognosis.

Simple SummaryIn prostate cancer diagnosis and prognosis, clinicians often must take decisions on which prostate cancer-suspected patients should undergo biopsy and which prostate cancer-diagnosed patients should undergo treatment, to overcome overdiagnosis and overtreatment. Many biomarker-based tests have been developed and commercialized in order to guide decision-making processes of clinicians. Since a variety of biomarker-based tests are currently available, this review provides an overview of all commercially available tests for prostate cancer diagnosis and prognosis. For the diagnostic setting, the PHI, 4K, MiPS, SelectMDx, ExoDx, Proclarix, ConfirmMDx, PCA3 and PCMT are discussed, while for the prognostic setting, the Prolaris, OncotypeDx and Decipher test are discussed. Following, an overview is provided of the studies available comparing the performance of biomarker tests. Next, the use of biomarker tests complementary to the use of multiparametric magnetic resonance imaging in diagnosis of prostate cancer is discussed, which is an upcoming tool in prostate cancer diagnosis.In the diagnosis and prognosis of prostate cancer (PCa), the serum prostate-specific antigen test is widely used but is associated with low specificity. Therefore, blood-, urinary- and tissue-based biomarker tests have been developed, intended to be used in the diagnostic and prognostic setting of PCa. This review provides an overview of commercially available biomarker tests developed to be used in several clinical stages of PCa management. In the diagnostic setting, the following tests can help selecting the right patients for initial and/or repeat biopsy: PHI, 4K, MiPS, SelectMDx, ExoDx, Proclarix, ConfirmMDx, PCA3 and PCMT. In the prognostic setting, the Prolaris, OncotypeDx and Decipher test can help in risk-stratification of patients regarding treatment decisions. Following, an overview is provided of the studies available comparing the performance of biomarker tests. However, only a small number of recently published head-to-head comparison studies are available. In contrast, recent research has focused on the use of biomarker tests in relation to the (complementary) use of multiparametric magnetic resonance imaging in PCa diagnosis.

Noninvasive Precision Screening of Prostate Cancer by Urinary Multimarker Sensor and Artificial Intelligence Analysis.

Screening for prostate cancer relies on the serum prostate-specific antigen test, which provides a high rate of false positives (80%). This results in a large number of unnecessary biopsies and subsequent overtreatment. Considering the frequency of the test, there is a critical unmet need of precision screening for prostate cancer. Here, we introduced a urinary multimarker biosensor with a capacity to learn to achieve this goal. The correlation of clinical state with the sensing signals from urinary multimarkers was analyzed by two common machine learning algorithms. As the number of biomarkers was increased, both algorithms provided a monotonic increase in screening performance. Under the best combination of biomarkers, the machine learning algorithms screened prostate cancer patients with more than 99% accuracy using 76 urine specimens. Urinary multimarker biosensor leveraged by machine learning analysis can be an important strategy of precision screening for cancers using a drop of bodily fluid.

Sojourn-time-corrected receiver operating characteristic curve (ROC) for prostate specific antigen (PSA) test in population-based prostate cancer screening

Evaluating the performance of serum prostate-specific antigen (PSA) test in population-based screening with receiver operating characteristics (ROC) curve often neglects the time dimension. Asymptomatic cases with negative PSA test would have been missed if sojourn time is not taken into account to allow for cases surfacing into the clinical phase. Data included 20,796 men with PSA test at the first screening round was used from population-based Finnish prostate cancer screening trial during 1996–1999. Cancers detected at the first screen, together with interval cancers ascertained during 4-year follow-up were expediently used to estimate sensitivity and specificity. A sojourn-time-corrected model was applied to estimating the possible false negative cases for those with PSA < 4 ng/ml for correcting the ROC curve. The estimated sensitivity estimate was reduced from 94.4% without correction to 68.8% with correction but the estimated specificity was identical (89.4% vs. 89.2%) at cutoff of 3 ng/ml. The corrected area under curve (AUC) [77.0% (74.9–79.1%)] of the PSA test was significantly lower than the uncorrected AUC [95.9% (95.3–96.6%)]. The failure of considering the time since last negative screen due to incomplete ascertainment for asymptomatic cancer led to the overestimation of PSA test performance that further affects the cut-off value of PSA tests for population-based prostate cancer screening.

Affinity Captured Urinary Extracellular Vesicles Provide mRNA and miRNA Biomarkers for Improved Accuracy of Prostate Cancer Detection: A Pilot Study.

Serum prostate-specific antigen (sPSA) testing has helped to increase early detection of and decrease mortality from prostate cancer. However, since sPSA lacks specificity, an invasive prostate tissue biopsy is required to confirm cancer diagnosis. Using urinary extracellular vesicles (EVs) as a minimally invasive biomarker source, our goal was to develop a biomarker panel able to distinguish prostate cancer from benign conditions with high accuracy. We enrolled 56 patients in our study, 28 negative and 28 positive for cancer based on tissue biopsy results. Using our Vn96 peptide affinity method, we isolated EVs from post-digital rectal exam urines and used quantitative polymerase chain reaction to measure several mRNA and miRNA targets. We identified a panel of seven mRNA biomarkers whose expression ratio discriminated non-cancer from cancer with an area under the curve (AUC) of 0.825, sensitivity of 75% and specificity of 84%. We also identified two miRNAs whose combined score yielded an AUC of 0.744. A model pairing the seven mRNA and two miRNA panels yielded an AUC of 0.843, sensitivity of 79% and specificity of 89%. Addition of EV-derived PCA3 levels and clinical characteristics to the biomarker model further improved test accuracy. An AUC of 0.955, sensitivity of 86% and specificity of 93% were obtained. Hence, Vn96-isolated urinary EVs are a clinically applicable and minimally invasive source of mRNA and miRNA biomarkers with potential to improve on the accuracy of prostate cancer screening and diagnosis.

A Panel of Urinary Volatile Biomarkers for Differential Diagnosis of Prostate Cancer from Other Urological Cancers.

Our group recently developed a urinary 6-biomarker panel for the diagnosis of prostate cancer (PCa) which has a higher level of accuracy compared to the serum prostate specific antigen (PSA) test. Herein, urine from an independent cohort of PCa patients and cancer-free controls was analyzed to further validate the discriminative power of that panel. Additionally, urine from patients diagnosed with bladder cancer (BC) and renal cancer (RC) were included to evaluate the site-specificity of the panel. Results confirmed the ability of the 6-biomarker panel to discriminate PCa patients from controls, but not from other urological cancers. To overcome this limitation, an untargeted approach was performed to unveil discriminant metabolites among the three cancer types. A 10-biomarker panel comprising the original panel plus four new metabolites was established to discriminate PCa from controls, BC, and RC, with 76% sensitivity, 90% specificity, and 92% accuracy. This improved panel also disclosed better accuracy than serum PSA test and provides the basis for a new non-invasive early detection tool for PCa.

Optimal Starting Age and Baseline Level for Repeat Tests: Economic Concerns of PSA Screening for Chinese Men – 10-Year Experience of a Single Center

Objective: To investigate the optimal age for the baseline serum prostate-specific antigen (PSA) test and for repeat screening and its economic burden in a single center in China. Materials and Methods: 35,533 men with PSA screening were retrospectively enrolled in this study. Follow-ups were conducted in 1,586 men with PSA >4 ng/mL, and receiver-operating characteristic (ROC) curves were employed to investigate the optimal cutoffs. Results: ROC analysis indicated that the optimal age for initial PSA screening was 57.5 years (AUC = 0.84), 62.5 years (AUC = 0.902), 60.5 years (AUC = 0.909), and 61.5 years (AUC = 0.890) for individuals with PSA >4 and >10 ng/mL, a diagnosis of prostate cancer (PCa), and clinically significant PCa defined as the focus events, respectively. For Chinese men aged 50–59, 60–69, and >70 years, the initial PSA levels of 1.305 ng/mL (AUC = 0.699), 1.975 ng/mL (AUC = 0.711), and 2.740 ng/mL (AUC = 0.720) might have a PSA velocity >0.75 ng/mL per year during the follow-up. In addition, the total cost amounts to CNY 13,609,260 in these cases, but only 60 of the 35,533 (0.17%) men gained benefit from PSA screening. Conclusion: In our opinion, the optimal starting age for initial PSA testing was 57.5 years. The necessity for repeat screening should be based on the first PSA level depending on age. A cost-­benefit analysis should be included in population-based screening.

Urinary spermine level as novel additional diagnostic marker of prostate cancer

Abstract Background prostate cancer (PC) is one of the most common male cancer in the world, and it is one of the leading causes of mortality and momentous public health impact in many developed countries. Nowadays, PSA (prostate-specific antigen) test is used as a famous serum test for screening of prostate cancer. However, PSA test isnt sensitive and specific enough, because its high levels do not always indicate the presence of a malignant process in the prostate, and low - about its absence. Some studies suggest to use concentration of spermine in the urine as a novel noninvasive marker for PC diagnostics. Methods Male patients age 51-79 with prostate cancer (I-IV stage) were enrolled. Diagnoses of all patients were established at the National Cancer Institute (Kyiv, Ukraine). Spermine concentration was determined in the morning urine samples of 38 patients with malignant tumors (I stage - 16%, II - 45%, III - 24%, IV - 15%) before treatment, 12 patients with prostate hyperplasia and 12 healthy men by ELISA kit. Results It was found that concentration of spermine in the urine in patients with prostate cancer was lower by 7-34 times in comparison with healthy men and lower by 5-13 times than in patients with prostate hyperplasia. The same results were obtained previously in peripheral blood of PC patients by the high pressure liquid chromatography (HPLC). Conclusion concentration of spermine in the urine shows potential to serve as a novel PC diagnostic non-invasive marker, which in turn can help to address the limited sensitivity and specificity problem of serum PSA test.